International Journal of Molecular Sciences

10 pages, 734 KiB

Open AccessCase Report

Techno-Economic Evaluation of Biodiesel Production from Waste Cooking Oil—A Case Study of Hong Kong

by Sanjib Kumar Karmee¹

, Raffel Dharma Patria² and Carol Sze Ki Lin^1,*

¹ School of Energy and Environment, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong

² Department of Chemical and Biomolecular Engineering, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong

Int. J. Mol. Sci. 2015, 16(3), 4362-4371; https://doi.org/10.3390/ijms16034362 - 18 Feb 2015

Cited by 125 | Viewed by 20519

Abstract

Fossil fuel shortage is a major challenge worldwide. Therefore, research is currently underway to investigate potential renewable energy sources. Biodiesel is one of the major renewable energy sources that can be obtained from oils and fats by transesterification. However, biodiesel obtained from vegetable [...] Read more.

Fossil fuel shortage is a major challenge worldwide. Therefore, research is currently underway to investigate potential renewable energy sources. Biodiesel is one of the major renewable energy sources that can be obtained from oils and fats by transesterification. However, biodiesel obtained from vegetable oils as feedstock is expensive. Thus, an alternative and inexpensive feedstock such as waste cooking oil (WCO) can be used as feedstock for biodiesel production. In this project, techno-economic analyses were performed on the biodiesel production in Hong Kong using WCO as a feedstock. Three different catalysts such as acid, base, and lipase were evaluated for the biodiesel production from WCO. These economic analyses were then compared to determine the most cost-effective method for the biodiesel production. The internal rate of return (IRR) sensitivity analyses on the WCO price and biodiesel price variation are performed. Acid was found to be the most cost-effective catalyst for the biodiesel production; whereas, lipase was the most expensive catalyst for biodiesel production. In the IRR sensitivity analyses, the acid catalyst can also acquire acceptable IRR despite the variation of the WCO and biodiesel prices. Full article

(This article belongs to the Special Issue Green Chemistry and the Biorefinery)

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7 pages, 663 KiB

Open AccessCommunication

Cell Membrane CD44v6 Levels in Squamous Cell Carcinoma of the Lung: Association with High Cellular Proliferation and High Concentrations of EGFR and CD44v5

by Álvaro Ruibal^1,2,3, Pablo Aguiar^1,2,*, María Carmen Del Río⁴, Matilde Isabel Nuñez², Virginia Pubul² and Michel Herranz^1,2

¹ Molecular Imaging Group, Faculty of Medicine, University of Santiago Compostela, R/de San Francisco, s/n., Santiago de Compostela 15782, Spain

² Nuclear Medicine Department, University Hospital Santiago Compostela (CHUS), R/Choupana, s/n., Santiago de Compostela 15706, Spain

³ Fundación Tejerina, C/José Abascal, 40, Madrid 28003, Spain

⁴ General Lab, Hospital Arquitecto Marcide, Ferrol, A Coruña 15405, Spain

Int. J. Mol. Sci. 2015, 16(3), 4372-4378; https://doi.org/10.3390/ijms16034372 - 18 Feb 2015

Cited by 6 | Viewed by 5368

Abstract

Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values [...] Read more.

Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

13 pages, 2778 KiB

Open AccessArticle

Hair-Growth-Promoting Effect of Conditioned Medium of High Integrin α₆ and Low CD 71 (α₆^bri/CD71^dim) Positive Keratinocyte Cells

by Chong Hyun Won¹, Yun-Mi Jeong², Sangjin Kang², Tae-Sung Koo³, So-Hyun Park⁴, Ki-Young Park⁵, Young-Kwan Sung⁶ and Jong-Hyuk Sung^7,*

¹ Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea

² Department of Applied Bioscience, CHA University, Seoul 135-081, Korea

³ Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 305-764, Korea

⁴ Coway Cosmetics R&D Center, Seoul 153-792, Korea

⁵ Asan Institute for Life Sciences, Seoul 138-736, Korea

⁶ Department of Immunology, School of Medicine, Kyungpook National University, Daegu 700-422, Korea

⁷ College of Pharmacy, Yonsei University, Incheon 406-840, Korea

Int. J. Mol. Sci. 2015, 16(3), 4379-4391; https://doi.org/10.3390/ijms16034379 - 19 Feb 2015

Cited by 21 | Viewed by 8717

Abstract

Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects [...] Read more.

Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor). A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells. Full article

(This article belongs to the Section Biochemistry)

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24 pages, 1619 KiB

Open AccessArticle

Assessing the Antimicrobial Activity of Polyisoprene Based Surfaces

by Hope Badawy¹, Jérôme Brunellière², Marina Veryaskina¹, Guillaume Brotons¹, Sophie Sablé³, Isabelle Lanneluc³

, Kelly Lambert², Pascal Marmey², Amy Milsted⁴, Teresa Cutright⁵, Arnaud Nourry¹, Jean-Luc Mouget^6,* and Pamela Pasetto^1,*

¹ LUNAM Université, Institut des Molécules et des Matériaux du Mans, UMR CNRS 6283, Université du Maine, Avenue Olivier Messiaen, 72085 Le Mans, France

² Centre de Transfert de Technologie du Mans, 20 rue Thalès de Milet, 72000 Le Mans, France

³ LIENSs, UMR CNRS 7266, Université de La Rochelle, Bât. Marie Curie, Av. Michel Crépeau, 17042 La Rochelle, France

⁴ Biology Department, University of Akron, Akron, OH 44325, USA

⁵ Department of Civil Engineering, University of Akron, Akron, OH 44325, USA

⁶ MMS-Mer, Molécules-Santé, FR CNRS 3473 IUML, Université du Maine, 72085 Le Mans, France

Int. J. Mol. Sci. 2015, 16(3), 4392-4415; https://doi.org/10.3390/ijms16034392 - 19 Feb 2015

Cited by 10 | Viewed by 8316

Abstract

There has been an intense research effort in the last decades in the field of biofouling prevention as it concerns many aspects of everyday life and causes problems to devices, the environment, and human health. Many different antifouling and antimicrobial materials have been [...] Read more.

There has been an intense research effort in the last decades in the field of biofouling prevention as it concerns many aspects of everyday life and causes problems to devices, the environment, and human health. Many different antifouling and antimicrobial materials have been developed to struggle against bacteria and other micro- and macro-organism attachment to different surfaces. However the “miracle solution” has still to be found. The research presented here concerns the synthesis of bio-based polymeric materials and the biological tests that showed their antifouling and, at the same time, antibacterial activity. The raw material used for the coating synthesis was natural rubber. The polyisoprene chains were fragmented to obtain oligomers, which had reactive chemical groups at their chain ends, therefore they could be modified to insert polymerizable and biocidal groups. Films were obtained by radical photopolymerization of the natural rubber derived oligomers and their structure was altered, in order to understand the mechanism of attachment inhibition and to increase the efficiency of the anti-biofouling action. The adhesion of three species of pathogenic bacteria and six strains of marine bacteria was studied. The coatings were able to inhibit bacterial attachment by contact, as it was verified that no detectable leaching of toxic molecules occurred. Full article

(This article belongs to the Special Issue Antimicrobial Polymers)

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13 pages, 671 KiB

Open AccessArticle

Pharmacogenetics Informed Decision Making in Adolescent Psychiatric Treatment: A Clinical Case Report

by Teri Smith^*, Susan Sharp, Ann M. Manzardo

and Merlin G. Butler

Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA

Int. J. Mol. Sci. 2015, 16(3), 4416-4428; https://doi.org/10.3390/ijms16034416 - 20 Feb 2015

Cited by 17 | Viewed by 10318

Abstract

Advances made in genetic testing and tools applied to pharmacogenetics are increasingly being used to inform clinicians in fields such as oncology, hematology, diabetes (endocrinology), cardiology and expanding into psychiatry by examining the influences of genetics on drug efficacy and metabolism. We present [...] Read more.

Advances made in genetic testing and tools applied to pharmacogenetics are increasingly being used to inform clinicians in fields such as oncology, hematology, diabetes (endocrinology), cardiology and expanding into psychiatry by examining the influences of genetics on drug efficacy and metabolism. We present a clinical case example of an adolescent male with anxiety, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder who did not tolerate numerous medications and dosages over several years in attempts to manage his symptoms. Pharmacogenetics testing was performed and DNA results on this individual elucidated the potential pitfalls in medication use because of specific pharmacodynamic and pharmacokinetic differences specifically involving polymorphisms of genes in the cytochrome p450 enzyme system. Future studies and reports are needed to further illustrate and determine the type of individualized medicine approach required to treat individuals based on their specific gene patterns. Growing evidence supports this biological approach for standard of care in psychiatry. Full article

(This article belongs to the Special Issue The Identification of the Genetic Components of Autism Spectrum Disorders)

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24 pages, 3703 KiB

Open AccessReview

Mammalian Introns: When the Junk Generates Molecular Diversity

by Florent Hubé^*

and Claire Francastel^*

CNRS UMR7216, Epigenetics and Cell Fate, Université Paris Diderot, Sorbonne Paris Cité, UMR7216 Epigénétique et Destin Cellulaire, Bâtiment Lamarck B, Case Courrier 7042, 35 rue Hélène Brion, 75013 Paris, France

Int. J. Mol. Sci. 2015, 16(3), 4429-4452; https://doi.org/10.3390/ijms16034429 - 20 Feb 2015

Cited by 53 | Viewed by 11976

Abstract

Introns represent almost half of the human genome, yet their vast majority is eliminated from eukaryotic transcripts through RNA splicing. Nevertheless, they feature key elements and functions that deserve further interest. At the level of DNA, introns are genomic segments that can shelter [...] Read more.

Introns represent almost half of the human genome, yet their vast majority is eliminated from eukaryotic transcripts through RNA splicing. Nevertheless, they feature key elements and functions that deserve further interest. At the level of DNA, introns are genomic segments that can shelter independent transcription units for coding and non-coding RNAs which transcription may interfere with that of the host gene, and regulatory elements that can influence gene expression and splicing itself. From the RNA perspective, some introns can be subjected to alternative splicing. Intron retention appear to provide some plasticity to the nature of the protein produced, its distribution in a given cell type and timing of its translation. Intron retention may also serve as a switch to produce coding or non-coding RNAs from the same transcription unit. Conversely, splicing of introns has been directly implicated in the production of small regulatory RNAs. Hence, splicing of introns also appears to provide plasticity to the type of RNA produced from a genetic locus (coding, non-coding, short or long). We addressed these aspects to add to our understanding of mechanisms that control the fate of introns and could be instrumental in regulating genomic output and hence cell fate. Full article

(This article belongs to the Special Issue Pre-mRNA Splicing)

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18 pages, 3392 KiB

Open AccessArticle

Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf

by Nu Ry Song^1,2,†, Jong-Eun Kim^1,2,†, Jun Seong Park^3,†, Jong Rhan Kim^1,2,†, Heerim Kang^1,2, Eunjung Lee^1,2,4, Young-Gyu Kang³, Joe Eun Son^1,2, Sang Gwon Seo^1,2, Yong Seok Heo⁵

and Ki Won Lee^1,2,*

¹ WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-742, Korea

² Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, Korea

³ Skin Research Institute, Amorepacific R&D Center, Yongin, 446-829, Korea

⁴ Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam 463-746, Korea

⁵ Department of Chemistry, Konkuk University, Seoul, 143-701, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 4453-4470; https://doi.org/10.3390/ijms16034453 - 20 Feb 2015

Cited by 40 | Viewed by 9119

Abstract

Licorice is a traditional botanical medicine, and has historically been commonly prescribed in Asia to treat various diseases. Glycyrrhizin (Gc), a triterpene compound, is the most abundant phytochemical constituent of licorice. However, high intake or long-term consumption of Gc has been associated with [...] Read more.

Licorice is a traditional botanical medicine, and has historically been commonly prescribed in Asia to treat various diseases. Glycyrrhizin (Gc), a triterpene compound, is the most abundant phytochemical constituent of licorice. However, high intake or long-term consumption of Gc has been associated with a number of side effects, including hypertension. However, the presence of alternative bioactive compounds in licorice with anti-carcinogenic effects has long been suspected. Licochalcone A (LicoA) is a prominent member of the chalcone family and can be isolated from licorice root. To date, there have been no reported studies on the suppressive effect of LicoA against solar ultraviolet (sUV)-induced cyclooxygenase (COX)-2 expression and the potential molecular mechanisms involved. Here, we show that LicoA, a major chalcone compound of licorice, effectively inhibits sUV-induced COX-2 expression and prostaglandin E2 PGE₂ generation through the inhibition of activator protein 1 AP-1 transcriptional activity, with an effect that is notably more potent than Gc. Western blotting analysis shows that LicoA suppresses sUV-induced phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinases (ERK)1/2/p90 ribosomal protein S6 kinase (RSK) in HaCaT cells. Moreover, LicoA directly suppresses the activity of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase kinase (MEK)1, and B-Raf, but not Raf-1 in cell-free assays, indicating that PI3K, MEK1, and B-Raf are direct molecular targets of LicoA. We also found that LicoA binds to PI3K and B-Raf in an ATP-competitive manner, although LicoA does not appear to compete with ATP for binding with MEK1. Collectively, these results provide insight into the biological action of LicoA, which may have potential for development as a skin cancer chemopreventive agent. Full article

(This article belongs to the Section Biochemistry)

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21 pages, 1373 KiB

Open AccessReview

Tumor Progression Locus 2 (Tpl2) Kinase as a Novel Therapeutic Target for Cancer: Double-Sided Effects of Tpl2 on Cancer

by Hye Won Lee^1,2,3, Han Yong Choi², Kyeung Min Joo^3,4,* and Do-Hyun Nam^1,3,*

¹ Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 135-710 Seoul, Korea

² Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 135-710 Seoul, Korea

³ Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 135-710 Seoul, Korea

⁴ Department of Anatomy and Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 135-710 Seoul, Korea

Int. J. Mol. Sci. 2015, 16(3), 4471-4491; https://doi.org/10.3390/ijms16034471 - 25 Feb 2015

Cited by 34 | Viewed by 9710

Abstract

Tumor progression locus 2 (Tpl2) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that conveys various intra- and extra-cellular stimuli to effector proteins of cells provoking adequate adoptive responses. Recent studies have elucidated that Tpl2 is an indispensable signal transducer as an [...] Read more.

Tumor progression locus 2 (Tpl2) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that conveys various intra- and extra-cellular stimuli to effector proteins of cells provoking adequate adoptive responses. Recent studies have elucidated that Tpl2 is an indispensable signal transducer as an MAP3K family member in diverse signaling pathways that regulate cell proliferation, survival, and death. Since tumorigenesis results from dysregulation of cellular proliferation, differentiation, and apoptosis, Tpl2 participates in many decisive molecular processes of tumor development and progression. Moreover, Tpl2 is closely associated with cytokine release of inflammatory cells, which has crucial effects on not only tumor cells but also tumor microenvironments. These critical roles of Tpl2 in human cancers make it an attractive anti-cancer therapeutic target. However, Tpl2 contradictorily works as a tumor suppressor in some cancers. The double-sided effects of Tpl2 originate from the specific upstream and downstream signaling environment of each tumor, since Tpl2 interacts with various signaling components. This review summarizes recent studies concerning the possible roles of Tpl2 in human cancers and considers its possibility as a therapeutic target, against which novel anti-cancer agents could be developed. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology 2014)

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20 pages, 2041 KiB

Open AccessArticle

Validation of Tuba1a as Appropriate Internal Control for Normalization of Gene Expression Analysis during Mouse Lung Development

by Aditi Mehta^1,2,3, Stephanie Dobersch^1,2,3, Reinhard H. Dammann^2,3,4, Saverio Bellusci^2,3,5,6, Olga N. Ilinskaya⁶, Thomas Braun^2,3,7 and Guillermo Barreto^1,2,3,6,*

¹ LOEWE Research Group Lung Cancer Epigenetic, Max-Planck-Institute for Heart and Lung Research, Parkstraße 1, 61231 Bad Nauheim, Germany

² Universities of Giessen and Marburg Lung Center (UGMLC), Aulweg 130, 35392 Giessen, Germany

³ German Center of Lung Research (DZL), Aulweg 130, 35392 Giessen, Germany

⁴ Institute for Genetics, Justus-Liebig-University, Heinrich-Buff-Ring 58, 35392 Giessen, Germany

⁵ Chair for Lung Matrix Remodeling, Excellence Cluster Cardio Pulmonary System, Aulweg 130, 35392 Giessen, Germany

⁶ Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St, 420008 Kazan, Russian Federation

⁷ Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Parkstraße 1, 61231 Bad Nauheim, Germany

Int. J. Mol. Sci. 2015, 16(3), 4492-4511; https://doi.org/10.3390/ijms16034492 - 25 Feb 2015

Cited by 25 | Viewed by 7540

Abstract

The expression ratio between the analysed gene and an internal control gene is the most widely used normalization method for quantitative RT-PCR (qRT-PCR) expression analysis. The ideal reference gene for a specific experiment is the one whose expression is not affected by the [...] Read more.

The expression ratio between the analysed gene and an internal control gene is the most widely used normalization method for quantitative RT-PCR (qRT-PCR) expression analysis. The ideal reference gene for a specific experiment is the one whose expression is not affected by the different experimental conditions tested. In this study, we validate the applicability of five commonly used reference genes during different stages of mouse lung development. The stability of expression of five different reference genes (Tuba1a, Actb Gapdh, Rn18S and Hist4h4) was calculated within five experimental groups using the statistical algorithm of geNorm software. Overall, Tuba1a showed the least variability in expression among the different stages of lung development, while Hist4h4 and Rn18S showed the maximum variability in their expression. Expression analysis of two lung specific markers, surfactant protein C (SftpC) and Clara cell-specific 10 kDA protein (Scgb1a1), normalized to each of the five reference genes tested here, confirmed our results and showed that incorrect reference gene choice can lead to artefacts. Moreover, a combination of two internal controls for normalization of expression analysis during lung development will increase the accuracy and reliability of results. Full article

(This article belongs to the Section Biochemistry)

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6 pages, 2982 KiB

Open AccessBrief Report

Thinopyrum ponticum Chromatin-Integrated Wheat Genome Shows Salt-Tolerance at Germination Stage

by Wen-Ye Yuan² and Motonori Tomita^1,2,*

¹ Research Institute of Green Science and Technology, Shizuoka University, 836, Ohya, Suruga-ku, Shizuoka 422-8529, Japan

² Molecular Genetics Laboratory, Faculty of Agriculture, Tottori University, 101, Minami 4-chome, Koyama-cho, Tottori 680-8553, Japan

Int. J. Mol. Sci. 2015, 16(3), 4512-4517; https://doi.org/10.3390/ijms16034512 - 26 Feb 2015

Cited by 9 | Viewed by 5489

Abstract

A wild wheatgrass, Thinopyrum ponticum (2n = 10x = 70), which exhibits substantially higher levels of salt tolerance than cultivated wheat, was employed to transfer its salt tolerance to common wheat by means of wide hybridization. A highly salt-tolerant wheat line [...] Read more.

A wild wheatgrass, Thinopyrum ponticum (2n = 10x = 70), which exhibits substantially higher levels of salt tolerance than cultivated wheat, was employed to transfer its salt tolerance to common wheat by means of wide hybridization. A highly salt-tolerant wheat line S148 (2n = 42) was obtained from the BC₃F₂ progenies between Triticum aestivum (2n = 42) and Th. ponticum. In the cross of S148 × salt-sensitive wheat variety Chinese Spring, the BC₄F₂ seeds at germination stage segregated into a ratio of 3 salt tolerant to 1 salt sensitive, indicating that the salt tolerance was conferred by a dominant gene block. Genomic in situ hybridization analysis revealed that S148 had a single pair of Th. ponticum–T. aestivum translocated chromosomes bearing the salt-tolerance. This is an initial step of molecular breeding for salt-tolerant wheat. Full article

(This article belongs to the Section Biochemistry)

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42 pages, 1796 KiB

Open AccessReview

tRNA Biology in Mitochondria

by Thalia Salinas-Giegé^1,†, Richard Giegé^2,† and Philippe Giegé^1,*,†

¹ Institut de Biologie Moléculaire des Plantes, CNRS and Université de Strasbourg, 12 rue du Général Zimmer, F-67084 Strasbourg Cedex, France

² Institut de Biologie Moléculaire et Cellulaire, CNRS and Université de Strasbourg, 15 rue René Descartes, F-67084 Strasbourg Cedex, France

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 4518-4559; https://doi.org/10.3390/ijms16034518 - 27 Feb 2015

Cited by 147 | Viewed by 16904

Abstract

Mitochondria are the powerhouses of eukaryotic cells. They are considered as semi-autonomous because they have retained genomes inherited from their prokaryotic ancestor and host fully functional gene expression machineries. These organelles have attracted considerable attention because they combine bacterial-like traits with novel features [...] Read more.

Mitochondria are the powerhouses of eukaryotic cells. They are considered as semi-autonomous because they have retained genomes inherited from their prokaryotic ancestor and host fully functional gene expression machineries. These organelles have attracted considerable attention because they combine bacterial-like traits with novel features that evolved in the host cell. Among them, mitochondria use many specific pathways to obtain complete and functional sets of tRNAs as required for translation. In some instances, tRNA genes have been partially or entirely transferred to the nucleus and mitochondria require precise import systems to attain their pool of tRNAs. Still, tRNA genes have also often been maintained in mitochondria. Their genetic arrangement is more diverse than previously envisaged. The expression and maturation of mitochondrial tRNAs often use specific enzymes that evolved during eukaryote history. For instance many mitochondria use a eukaryote-specific RNase P enzyme devoid of RNA. The structure itself of mitochondrial encoded tRNAs is also very diverse, as e.g., in Metazoan, where tRNAs often show non canonical or truncated structures. As a result, the translational machinery in mitochondria evolved adapted strategies to accommodate the peculiarities of these tRNAs, in particular simplified identity rules for their aminoacylation. Here, we review the specific features of tRNA biology in mitochondria from model species representing the major eukaryotic groups, with an emphasis on recent research on tRNA import, maturation and aminoacylation. Full article

(This article belongs to the Special Issue Functions of Transfer RNAs)

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21 pages, 752 KiB

Open AccessReview

Roles of Ubiquitination and SUMOylation on Prostate Cancer: Mechanisms and Clinical Implications

by Zhenbang Chen^* and Wenfu Lu

Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA

Int. J. Mol. Sci. 2015, 16(3), 4560-4580; https://doi.org/10.3390/ijms16034560 - 27 Feb 2015

Cited by 47 | Viewed by 14773

Abstract

The initiation and progression of human prostate cancer are highly associated with aberrant dysregulations of tumor suppressors and proto-oncogenes. Despite that deletions and mutations of tumor suppressors and aberrant elevations of oncogenes at the genetic level are reported to cause cancers, emerging evidence [...] Read more.

The initiation and progression of human prostate cancer are highly associated with aberrant dysregulations of tumor suppressors and proto-oncogenes. Despite that deletions and mutations of tumor suppressors and aberrant elevations of oncogenes at the genetic level are reported to cause cancers, emerging evidence has revealed that cancer progression is largely regulated by posttranslational modifications (PTMs) and epigenetic alterations. PTMs play critical roles in gene regulation, cellular functions, tissue development, diseases, malignant progression and drug resistance. Recent discoveries demonstrate that ubiquitination and SUMOylation are complicated but highly-regulated PTMs, and make essential contributions to diseases and cancers by regulation of key factors and signaling pathways. Ubiquitination and SUMOylation pathways can be differentially modulated under various stimuli or stresses in order to produce the sustained oncogenic potentials. In this review, we discuss some new insights about molecular mechanisms on ubiquitination and SUMOylation, their associations with diseases, oncogenic impact on prostate cancer (PCa) and clinical implications for PCa treatment. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology)

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19 pages, 699 KiB

Open AccessReview

Recent Advances in Proteomic Studies of Adipose Tissues and Adipocytes

by Eun Young Kim^1,†, Won Kon Kim^1,2,†, Kyoung-Jin Oh¹

, Baek Soo Han^1,2, Sang Chul Lee^1,2,* and Kwang-Hee Bae^1,2,*

¹ Functional Genomics Research Center, KRIBB, Daejeon 305-806, Korea

² Department of Functional Genomics, University of Science and Technology of Korea, Daejeon 305-806, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 4581-4599; https://doi.org/10.3390/ijms16034581 - 27 Feb 2015

Cited by 37 | Viewed by 7972

Abstract

Obesity is a chronic disease that is associated with significantly increased levels of risk of a number of metabolic disorders. Despite these enhanced health risks, the worldwide prevalence of obesity has increased dramatically over the past few decades. Obesity is caused by the [...] Read more.

Obesity is a chronic disease that is associated with significantly increased levels of risk of a number of metabolic disorders. Despite these enhanced health risks, the worldwide prevalence of obesity has increased dramatically over the past few decades. Obesity is caused by the accumulation of an abnormal amount of body fat in adipose tissue, which is composed mostly of adipocytes. Thus, a deeper understanding of the regulation mechanism of adipose tissue and/or adipocytes can provide a clue for overcoming obesity-related metabolic diseases. In this review, we describe recent advances in the study of adipose tissue and/or adipocytes, focusing on proteomic approaches. In addition, we suggest future research directions for proteomic studies which may lead to novel treatments of obesity and obesity-related diseases. Full article

(This article belongs to the Special Issue Advances in Proteomic Research)

15 pages, 975 KiB

Open AccessReview

Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia

by Keiichi Matsubara^1,*, Takashi Higaki², Yuko Matsubara¹ and Akihiro Nawa¹

¹ Department of Obstetrics and Gynecology, Ehime University School of Medicine, Ehime 791-0295, Japan

² Department of Pediatrics, Ehime University School of Medicine, Ehime 791-0295, Japan

Int. J. Mol. Sci. 2015, 16(3), 4600-4614; https://doi.org/10.3390/ijms16034600 - 2 Mar 2015

Cited by 189 | Viewed by 14769

Abstract

Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue [...] Read more.

Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O₂⁻) rapidly inactivates NO and forms peroxynitrite (ONOO⁻). It is known that ONOO⁻ accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)

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13 pages, 725 KiB

Open AccessReview

Methods for Biomimetic Remineralization of Human Dentine: A Systematic Review

by Chris Ying Cao^1,2, May Lei Mei¹, Quan-Li Li², Edward Chin Man Lo¹

and Chun Hung Chu^1,*

¹ Faculty of Dentistry, The University of Hong Kong, Hong Kong, China

² Key Laboratory of Oral Diseases Research of Anhui Province, Stomatological Hospital & College, Anhui Medical University, Hefei 230032, China

Int. J. Mol. Sci. 2015, 16(3), 4615-4627; https://doi.org/10.3390/ijms16034615 - 2 Mar 2015

Cited by 115 | Viewed by 12212

Abstract

This study aimed to review the laboratory methods on biomimetic remineralization of demineralized human dentine. A systematic search of the publications in the PubMed, TRIP, and Web of Science databases was performed. Titles and abstracts of initially identified publications were screened. Clinical trials, [...] Read more.

This study aimed to review the laboratory methods on biomimetic remineralization of demineralized human dentine. A systematic search of the publications in the PubMed, TRIP, and Web of Science databases was performed. Titles and abstracts of initially identified publications were screened. Clinical trials, reviews, non-English articles, resin-dentine interface studies, hybrid layer studies, hybrid scaffolds studies, and irrelevant studies were excluded. The remaining papers were retrieved with full texts. Manual screening was conducted on the bibliographies of remaining papers to identify relevant articles. A total of 716 studies were found, and 690 were excluded after initial screening. Two articles were identified from the bibliographies of the remaining papers. After retrieving the full text, 23 were included in this systematic review. Sixteen studies used analogues to mimic the functions of non-collagenous proteins in biomineralization of dentine, and four studies used bioactive materials to induce apatite formation on demineralized dentine surface. One study used zinc as a bioactive element, one study used polydopamine, and another study constructed an agarose hydrogel system for biomimetic mineralization of dentine. Many studies reported success in biomimetic mineralization of dentine, including the use of non-collagenous protein analogues, bioactive materials, or elements and agarose hydrogel system. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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14 pages, 3953 KiB

Open AccessArticle

Chloroplast-Expressed MSI-99 in Tobacco Improves Disease Resistance and Displays Inhibitory Effect against Rice Blast Fungus

by Yun-Peng Wang^1,2, Zheng-Yi Wei²

, Yu-Ying Zhang^2,3, Chun-Jing Lin², Xiao-Fang Zhong², Yue-Lin Wang², Jing-Yong Ma¹, Jian Ma^1,* and Shao-Chen Xing^2,*

¹ Faculty of Agronomy, Jilin Agricultural University, No. 2888 Xincheng Street, Changchun 130118, China

² Agro-Biotechnology Research Institute, Jilin Academy of Agricultural Sciences, No. 1363 Shengtai Street, Changchun 130033, China

³ College of Biological Sciences, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100094, China

Int. J. Mol. Sci. 2015, 16(3), 4628-4641; https://doi.org/10.3390/ijms16034628 - 2 Mar 2015

Cited by 22 | Viewed by 7545

Abstract

Rice blast is a major destructive fungal disease that poses a serious threat to rice production and the improvement of blast resistance is critical to rice breeding. The antimicrobial peptide MSI-99 has been suggested as an antimicrobial peptide conferring resistance to bacterial and [...] Read more.

Rice blast is a major destructive fungal disease that poses a serious threat to rice production and the improvement of blast resistance is critical to rice breeding. The antimicrobial peptide MSI-99 has been suggested as an antimicrobial peptide conferring resistance to bacterial and fungal diseases. Here, a vector harboring the MSI-99 gene was constructed and introduced into the tobacco chloroplast genome via particle bombardment. Transformed plants were obtained and verified to be homoplastomic by PCR and Southern hybridization. In planta assays demonstrated that the transgenic tobacco plants displayed an enhanced resistance to the fungal disease. The evaluation of the antimicrobial activity revealed that the crude protein extracts from the transgenic plants manifested an antimicrobial activity against E. coli, even after incubation at 120 °C for 20 min, indicating significant heat stability of MSI-99. More importantly, the MSI-99-containing protein extracts were firstly proved in vitro and in vivo to display significant suppressive effects on two rice blast isolates. These findings provide a strong basis for the development of new biopesticides to combat rice blast. Full article

(This article belongs to the Special Issue Plant Microbe Interaction)

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24 pages, 6283 KiB

Open AccessArticle

Nerve Demyelination Increases Metabotropic Glutamate Receptor Subtype 5 Expression in Peripheral Painful Mononeuropathy

by Miau-Hwa Ko¹, Yu-Lin Hsieh²

, Sung-Tsang Hsieh^3,4,† and To-Jung Tseng^5,6,*,†

¹ Department of Anatomy, College of Medicine, China Medical University, Taichung 40402, Taiwan

² Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

³ Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei 10051, Taiwan

⁴ Department of Neurology, National Taiwan University Hospital, Taipei 10002, Taiwan

⁵ Department of Anatomy, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

⁶ Department of Medical Education, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 4642-4665; https://doi.org/10.3390/ijms16034642 - 2 Mar 2015

Cited by 20 | Viewed by 6855

Abstract

Wallerian degeneration or nerve demyelination, arising from spinal nerve compression, is thought to bring on chronic neuropathic pain. The widely distributed metabotropic glutamate receptor subtype 5 (mGluR5) is involved in modulating nociceptive transmission. The purpose of this study was to investigate the potential [...] Read more.

Wallerian degeneration or nerve demyelination, arising from spinal nerve compression, is thought to bring on chronic neuropathic pain. The widely distributed metabotropic glutamate receptor subtype 5 (mGluR5) is involved in modulating nociceptive transmission. The purpose of this study was to investigate the potential effects of mGluR5 on peripheral hypersensitivities after chronic constriction injury (CCI). Sprague-Dawley rats were operated on with four loose ligatures around the sciatic nerve to induce thermal hyperalgesia and mechanical allodynia. Primary afferents in dermis after CCI exhibited progressive decreases, defined as partial cutaneous denervation; importantly, mGluR5 expressions in primary afferents were statistically increased. CCI-induced neuropathic pain behaviors through the intraplantar injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, were dose-dependently attenuated. Furthermore, the most increased mGluR5 expressions in primary afferents surrounded by reactive Schwann cells were observed at the distal CCI stumps of sciatic nerves. In conclusion, these results suggest that nerve demyelination results in the increases of mGluR5 expression in injured primary afferents after CCI; and further suggest that mGluR5 represents a main therapeutic target in developing pharmacological strategies to prevent peripheral hypersensitivities. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Pain)

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16 pages, 2089 KiB

Open AccessArticle

A Hyaluronan-Based Scaffold for the in Vitro Construction of Dental Pulp-Like Tissue

by Letizia Ferroni^1,†, Chiara Gardin^1,†, Stefano Sivolella²

, Giulia Brunello²

, Mario Berengo², Adriano Piattelli³, Eriberto Bressan² and Barbara Zavan^1,*

¹ Department of Biomedical Sciences, University of Padova, Viale Giuseppe Colombo, 3, 35131 Padova, Italy

² Department of Neurosciences, University of Padova, Via Giustiniani, 2, 35131 Padova, Italy

³ Department of Stomatology and Biotechnologies, University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 4666-4681; https://doi.org/10.3390/ijms16034666 - 2 Mar 2015

Cited by 52 | Viewed by 8870 | Correction

Abstract

Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based [...] Read more.

Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D) hyaluronan scaffold and human dental pulp stem cells (DPSCs) to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF) staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue. Full article

(This article belongs to the Special Issue Artificial Organs)

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16 pages, 12409 KiB

Open AccessArticle

The Anti-TNF-α Antibody Infliximab Inhibits the Expression of Fat-Transporter-Protein FAT/CD36 in a Selective Hepatic-Radiation Mouse Model

by Gesa Martius¹, Silke Cameron¹, Margret Rave-Fränk², Clemens F. Hess², Hendrik A. Wolff² and Ihtzaz A. Malik^1,*

¹ Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, Robert-Koch-Strasse 40, Goettingen 37075, Niedersachsen, Germany

² Department of Radiotherapy and Radiooncology, University Medical Center Goettingen, Robert-Koch-Strasse 40, Goettingen 37075, Niedersachsen, Germany

Int. J. Mol. Sci. 2015, 16(3), 4682-4697; https://doi.org/10.3390/ijms16034682 - 2 Mar 2015

Cited by 12 | Viewed by 8820

Abstract

Previously, we reported a radiation-induced inflammation triggering fat-accumulation through fatty-acid-translocase/cluster of differentiation protein 36 (FAT/CD36) in rat liver. Furthermore, inhibition of radiation-induced FAT/CD36-expression by anti-tumor necrosis factor-α (anti-TNF-α) (infliximab) was shown in vitro. The current study investigates fat-accumulation in a mouse-model of [...] Read more.

Previously, we reported a radiation-induced inflammation triggering fat-accumulation through fatty-acid-translocase/cluster of differentiation protein 36 (FAT/CD36) in rat liver. Furthermore, inhibition of radiation-induced FAT/CD36-expression by anti-tumor necrosis factor-α (anti-TNF-α) (infliximab) was shown in vitro. The current study investigates fat-accumulation in a mouse-model of single-dose liver-irradiation (25-Gray) and the effect of anti-TNF-α-therapy on FAT/CD36 gene-expression. Mice livers were selectively irradiated in vivo in presence or absence of infliximab. Serum- and hepatic-triglycerides, mRNA, and protein were analyzed by colorimetric assays, RT-PCR, Immunofluorescence and Western-Blot, respectively. Sudan-staining was used demonstrating fat-accumulation in tissue. In mice livers, early (1–3 h) induction of TNF-α-expression, a pro-inflammatory cytokine, was observed. It was followed by elevated hepatic-triglyceride level (6–12 h), compared to sham-irradiated controls. In contrast, serum-triglyceride level was decreased at these time points. Similar to triglyceride level in mice livers, Sudan staining of liver cryosections showed a quick (6–12 h) increase of fat-droplets after irradiation. Furthermore, expression of fat-transporter-protein FAT/CD36 was increased at protein level caused by radiation or TNF-α. TNF-α-blockage by anti-TNF-α showed an early inhibition of radiation-induced FAT/CD36 expression in mice livers. Immunohistochemistry showed basolateral and cytoplasmic expression of FAT/CD36 in hepatocytes. Moreover, co-localization of FAT/CD36 was detected with α-smooth muscle actin (α-SMA⁺) cells and F4/80⁺ macrophages. In summary, hepatic-radiation triggers fat-accumulation in mice livers, involving acute-phase-processes. Accordingly, anti-TNF-α-therapy prevented early radiation-induced expression of FAT/CD36 in vivo. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 2697 KiB

Open AccessArticle

Knockdown of UbcH10 Enhances the Chemosensitivity of Dual Drug Resistant Breast Cancer Cells to Epirubicin and Docetaxel

by Cheng Wang^1,*, Yun-Hao Pan¹, Ming Shan¹, Ming Xu², Jia-Lin Bao¹ and Li-Ming Zhao^3,*

¹ Department of Breast Surgery, Central Hospital of Huangpu District, Shanghai 20002, China

² Department of Pathology, Central Hospital of Huangpu District, Shanghai 20002, China

³ Department of Respiratory Disease, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai 200433, China

Int. J. Mol. Sci. 2015, 16(3), 4698-4712; https://doi.org/10.3390/ijms16034698 - 2 Mar 2015

Cited by 24 | Viewed by 6996

Abstract

Breast cancer is one of the most common and lethal cancers in women. As a hub gene involved in a diversity of tumors, the ubiquitin-conjugating enzyme H10 (UbcH10), may also play some roles in the genesis and development of breast cancer. In the [...] Read more.

Breast cancer is one of the most common and lethal cancers in women. As a hub gene involved in a diversity of tumors, the ubiquitin-conjugating enzyme H10 (UbcH10), may also play some roles in the genesis and development of breast cancer. In the current study, we found that the expression of UbcH10 was up-regulated in some breast cancer tissues and five cell lines. We established a dual drug resistant cell line MCF-7/EPB (epirubicin)/TXT (docetaxel) and a lentiviral system expressing UbcH10 shRNA to investigate the effects of UbcH10 knockdown on the chemosensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel. The knockdown of UbcH10 inhibited the proliferation of both MCF-7 and MCF-7/EPB/TXT cells, due to the G1 phase arrest in cell cycle. Furthermore, UbcH10 knockdown increased the sensitivity of MCF-7/EPB/TXT cells to epirubicin and docetaxel and promoted the apoptosis induced by these two drugs. Protein detection showed that, in addition to inhibiting the expression of Ki67 and cyclin D1, UbcH10 RNAi also impaired the increased BCL-2 and MDR-1 expression levels in MCF-7/EPB/TXT cells, which may contribute to abating the drug resistance in the breast cancer cells. Our research in the current study demonstrated that up-regulation of UbcH10 was involved in breast cancer and its knockdown can inhibit the growth of cancer cells and increase the chemosensitivity of the dual drug resistant breast cancer cells to epirubicin and docetaxel, suggesting that UbcH10 may be a promising target for the therapy of breast cancer. Full article

(This article belongs to the Special Issue Molecular Classification of Human Cancer and Its Role in Tailored Cancer Therapy)

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18 pages, 6710 KiB

Open AccessArticle

Proteome Analysis of Dormancy-Released Seeds of Fraxinus mandshurica Rupr. in Response to Re-Dehydration under Different Conditions

by Peng Zhang¹, Di Liu^1,2,*, Hailong Shen¹, Yuhua Li³ and Yuzhe Nie³

¹ State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, Harbin 150040, China

² Agricultural college, Yanbian University, Yanji 133002, China

³ College of Life Science, Daqing Bio-tech Research Institute, Northeast Forestry University, Harbin 150040, China

Int. J. Mol. Sci. 2015, 16(3), 4713-4730; https://doi.org/10.3390/ijms16034713 - 2 Mar 2015

Cited by 9 | Viewed by 7079

Abstract

Desiccation tolerance is the ability of orthodox seeds to achieve equilibrium with atmospheric relative humidity and to survive in this state. Understanding how orthodox seeds respond to dehydration is important for improving quality and long-term storage of seeds under low temperature and drought [...] Read more.

Desiccation tolerance is the ability of orthodox seeds to achieve equilibrium with atmospheric relative humidity and to survive in this state. Understanding how orthodox seeds respond to dehydration is important for improving quality and long-term storage of seeds under low temperature and drought stress conditions. Long-term storage of seeds is an artificial situation, because in most natural situations a seed that has been shed may not remain in a desiccated state for very long, and if dormant it may undergo repeated cycles of hydration. Different types of seeds are differentially sensitive to desiccation and this directly affects long-term storage. For these reasons, many researchers are investigating loss of desiccation tolerance during orthodox seed development to understand how it is acquired. In this study, the orthodox seed proteome response of Fraxinus mandshurica Rupr. to dehydration (to a relative water content of 10%, which mimics seed dehydration) was investigated under four different conditions viz. 20 °C; 20 °C with silica gel; 1 °C; and 1 °C after pretreatment with Ca²⁺. Proteins from seeds dehydrated under different conditions were extracted and separated by two-dimensional difference gel electrophoresis (2D-DIGE). A total of 2919 protein spots were detected, and high-resolution 2D-DIGE indicated there were 27 differentially expressed. Seven of these were identified using MALDI TOF/TOF mass spectrometry. Inferences from bioinformatics annotations of these proteins established the possible involvement of detoxifying enzymes, transport proteins, and nucleotide metabolism enzymes in response to dehydration. Of the seven differentially abundant proteins, the amounts of six were down-regulated and one was up-regulated. Also, a putative acyl-coenzyme A oxidase of the glyoxylate cycle increased in abundance. In particular, the presence of kinesin-1, a protein important for regulation and cargo interaction, was up-regulated in seeds exposed to low temperature dehydration. Kinesin-1 is present in all major lineages, but it is rarely detected in seed desiccation tolerance of woody species. These observations provide new insight into the proteome of seeds in deep dormancy under different desiccation conditions. Full article

(This article belongs to the Special Issue Advances in Proteomic Research)

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13 pages, 722 KiB

Open AccessArticle

Discovery of a Potent Anti-Yeast Triterpenoid Saponin, Clematoside-S from Urena lobata L.

by Xiao-Ling Gao^1,†, Ying Liao^2,†, Jie Wang^3,†, Xiao-Yan Liu^3,†, Kai Zhong³, Yi-Na Huang⁴, Hong Gao³, Bo Gao^4,* and Zheng-Jun Xu^1,*

¹ Rice Research Institute, Sichuan Agricultural University, Wenjiang 611130, China

² College of Life Science, Sichuan Normal University, Chengdu 610101, China

³ College of Light Industry, Textile and Food Engineering, Sichuan University, Chengdu 610065, China

⁴ West China School of Public Health, Sichuan University, Chengdu 610041, China

^† These authors contribute equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 4731-4743; https://doi.org/10.3390/ijms16034731 - 2 Mar 2015

Cited by 8 | Viewed by 6480

Abstract

Urena lobata has been used as a traditional medicinal plant in India and China. In this study, we investigated the antimicrobial activity and isolated the active compound from the leaves of U. lobata. The 80% ethanol extract from U. lobata [...] Read more.

Urena lobata has been used as a traditional medicinal plant in India and China. In this study, we investigated the antimicrobial activity and isolated the active compound from the leaves of U. lobata. The 80% ethanol extract from U. lobata leaves showed an effective anti-yeast activity against Saccharomyces cerevisiae (S. cerevisiae) strains. Using a combination of chromatographic methods, (−)-trachelogenin (1) and clematoside-S (2) were isolated from this plant for the first time, and their chemical structure was identified by mass spectrometry (MS) and extensive nuclear magnetic resonance (NMR) data analysis. In addition, 1 was found to be inactive against all of the test microorganisms in the antimicrobial assay, whereas 2 exhibits a specific anti-yeast activity against S. cerevisiae strains with diameter of inhibition zones in the range from 11 to 20 mm. Furthermore, the MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values of 2 against S. cerevisiae strains were detected to be in the ranges of 0.61 to 9.8 μg/mL and 2.42 to 9.8 μg/mL, respectively. This is the first report of 2 with a specific anti-yeast activity. The above result suggests the potential application of U. lobata to be used as a natural anti-yeast agent in food preservation. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 760 KiB

Open AccessArticle

Transcriptome Analysis in Rat Kidneys: Importance of Genes Involved in Programmed Hypertension

by You-Lin Tain^1,2,*

, Li-Tung Huang^1,3

, Julie Y. H. Chan² and Chien-Te Lee⁴

¹ Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan

² Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan

³ Department of Traditional Chinese Medicine, Chang Gung University, Linkow 244, Taiwan

⁴ Division of Nephrology, Departments of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan

Int. J. Mol. Sci. 2015, 16(3), 4744-4758; https://doi.org/10.3390/ijms16034744 - 2 Mar 2015

Cited by 50 | Viewed by 6778

Abstract

Suboptimal conditions in pregnancy can elicit long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether there are common genes and pathways in the kidney are responsible for generating programmed hypertension among three different models using [...] Read more.

Suboptimal conditions in pregnancy can elicit long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether there are common genes and pathways in the kidney are responsible for generating programmed hypertension among three different models using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received dexamethasone (DEX, 0.1 mg/kg) from gestational day 16 to 22, 60% high-fructose (HF) diet, or N^G-nitro-l-arginine-methyester (l-NAME, 60 mg/kg/day) to conduct DEX, HF, or l-NAME model respectively. All three models elicited programmed hypertension in adult male offspring. We observed five shared genes (Bcl6, Dmrtc1c, Egr1, Inmt, and Olr1668) among three different models. The identified differential genes (DEGs) that are related to regulation of blood pressure included Aqp2, Ptgs1, Eph2x, Hba-a2, Apln, Guca2b, Hmox1, and Npy. RNA-Seq identified genes in arachidonic acid metabolism are potentially gatekeeper genes contributing to programmed hypertension. In addition, HF and DEX increased expression and activity of soluble epoxide hydrolase (Ephx2 gene encoding protein). Conclusively, the DEGs in arachidonic acid metabolism are potentially gatekeeper genes in programmed hypertension. The roles of DEGs identified by the RNA-Seq in this study deserve further clarification, to develop the potential interventions in the prevention of programmed hypertension. Full article

(This article belongs to the Special Issue Advances in Reproductive Biology)

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15 pages, 1236 KiB

Open AccessArticle

Molecular Characterization of Vitellogenin and Its Receptor Genes from Citrus Red Mite, Panonychus citri (McGregor)

by Rui Zhong, Tian-Bo Ding, Jin-Zhi Niu, Wen-Kai Xia, Chong-Yu Liao, Wei Dou and Jin-Jun Wang^*

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China

Int. J. Mol. Sci. 2015, 16(3), 4759-4773; https://doi.org/10.3390/ijms16034759 - 2 Mar 2015

Cited by 21 | Viewed by 6883

Abstract

The production and uptake of yolk protein play an important role in the reproduction of all oviparous organisms. Vitellogenin (Vg) is the precursor of vitellin (Vn), which is the major egg storage protein, and vitellogenin receptor (VgR) is a necessary protein for the [...] Read more.

The production and uptake of yolk protein play an important role in the reproduction of all oviparous organisms. Vitellogenin (Vg) is the precursor of vitellin (Vn), which is the major egg storage protein, and vitellogenin receptor (VgR) is a necessary protein for the uptake of Vg into developing oocytes. In this paper, we characterize the full-length Vg and VgR, PcVg1 and PcVgR, respectively, of the citrus red mite Panonychus citri (McGregor). The PcVg1 cDNA is 5748 nucleotides (nt) with a 5553-nt open reading frame (ORF) coding for 1851 amino acids (aa), and the PcVgR is 6090 nt, containing an intact ORF of 5673 nt coding an expected protein of 1891 aa. The PcVg1 aa sequence shows a typical GLCG domain and several K/RXXR cleavage sites, and PcVgR comprises two ligand-binding domains, two epidermal growth factor (EGF)-like regions containing YWTD motifs, a transmembrane domain, and a cytoplasmic domain. An analysis of the aa sequences and phylogenetics implied that both genes were genetically distinct from those of ticks and insects. The transcriptional profiles determined by real-time quantitative PCR in different developmental stages showed that both genes present the same expressional tendencies in eggs, larvae, nymphs, and adults. This suggested that the biosynthesis and uptake of PcVg occurs coordinately. The strong reproductive capacity of P. citri has been hypothesized as an important factor in its resistance; consequently, understanding the molecular mechanisms regulating Vg and VgR are fundamental for mite control. Full article

(This article belongs to the Section Biochemistry)

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12 pages, 877 KiB

Open AccessArticle

Efficient Prediction of Progesterone Receptor Interactome Using a Support Vector Machine Model

by Ji-Long Liu^*, Ying Peng and Yong-Sheng Fu

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China

Int. J. Mol. Sci. 2015, 16(3), 4774-4785; https://doi.org/10.3390/ijms16034774 - 3 Mar 2015

Cited by 3 | Viewed by 5691

Abstract

Protein-protein interaction (PPI) is essential for almost all cellular processes and identification of PPI is a crucial task for biomedical researchers. So far, most computational studies of PPI are intended for pair-wise prediction. Theoretically, predicting protein partners for a single protein is likely [...] Read more.

Protein-protein interaction (PPI) is essential for almost all cellular processes and identification of PPI is a crucial task for biomedical researchers. So far, most computational studies of PPI are intended for pair-wise prediction. Theoretically, predicting protein partners for a single protein is likely a simpler problem. Given enough data for a particular protein, the results can be more accurate than general PPI predictors. In the present study, we assessed the potential of using the support vector machine (SVM) model with selected features centered on a particular protein for PPI prediction. As a proof-of-concept study, we applied this method to identify the interactome of progesterone receptor (PR), a protein which is essential for coordinating female reproduction in mammals by mediating the actions of ovarian progesterone. We achieved an accuracy of 91.9%, sensitivity of 92.8% and specificity of 91.2%. Our method is generally applicable to any other proteins and therefore may be of help in guiding biomedical experiments. Full article

(This article belongs to the Special Issue Proteins and Protein-Ligand Interactions)

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14 pages, 2959 KiB

Open AccessArticle

Real-Time Duplex Applications of Loop-Mediated AMPlification (LAMP) by Assimilating Probes

by Ryo Kubota^1,2,* and Daniel M. Jenkins²

¹ Diagenetix, Inc., Honolulu, HI 96822, USA

² Department of Molecular Biosciences and Bioengineering, University of Hawai'.i, Mānoa, 1955 East-West Road, Honolulu, HI 96822, USA

Int. J. Mol. Sci. 2015, 16(3), 4786-4799; https://doi.org/10.3390/ijms16034786 - 3 Mar 2015

Cited by 67 | Viewed by 7963

Abstract

Isothermal nucleic-acid amplification methods such as Loop-Mediated isothermal AMPlification (LAMP) are increasingly appealing alternatives to PCR for use in portable diagnostic system due to the low cost, weight, and power requirements of the instrumentation. As such, interest in developing new probes and other [...] Read more.

Isothermal nucleic-acid amplification methods such as Loop-Mediated isothermal AMPlification (LAMP) are increasingly appealing alternatives to PCR for use in portable diagnostic system due to the low cost, weight, and power requirements of the instrumentation. As such, interest in developing new probes and other functionality based on the LAMP reaction has been intense. Here, we report on the development of duplexed LAMP assays for pathogen detection using spectrally unique Assimilating Probes. As proof of principle, we used a reaction for Salmonella enterica as a model coupled with a reaction for λ-phage DNA as an internal control, as well as a duplexed assay to sub-type specific quarantine strains of the bacterial wilt pathogen Ralstonia solanacearum. Detection limits for bacterial DNA analyzed in individual reactions was less than 100 genomic equivalents in all cases, and increased by one to two orders of magnitude when reactions were coupled in duplexed formats. Even so, due to the more robust activity of newly available strand-displacing polymerases, the duplexed assays reported here were more powerful than analogous individual reactions reported only a few years ago, and represent a significant advance for incorporation of internal controls to validate assay results in the field. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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14 pages, 1133 KiB

Open AccessReview

Extracellular Vesicles in Alzheimer’s Disease: Friends or Foes? Focus on Aβ-Vesicle Interaction

by Pooja Joshi¹, Luisa Benussi², Roberto Furlan³, Roberta Ghidoni² and Claudia Verderio^1,4,*

¹ CNR Institute of Neuroscience, via Vanvitelli 32, 20129 Milano, Italy

² Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy

³ Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milano, Italy

⁴ IRCCS Humanitas, via Manzoni 56, 20089 Rozzano, Italy

Int. J. Mol. Sci. 2015, 16(3), 4800-4813; https://doi.org/10.3390/ijms16034800 - 3 Mar 2015

Cited by 88 | Viewed by 10974

Abstract

The intercellular transfer of amyloid-β (Aβ) and tau proteins has received increasing attention in Alzheimer’s disease (AD). Among other transfer modes, Aβ and tau dissemination has been suggested to occur through release of Extracellular Vesicles (EVs), which may facilitate delivery of pathogenic proteins [...] Read more.

The intercellular transfer of amyloid-β (Aβ) and tau proteins has received increasing attention in Alzheimer’s disease (AD). Among other transfer modes, Aβ and tau dissemination has been suggested to occur through release of Extracellular Vesicles (EVs), which may facilitate delivery of pathogenic proteins over large distances. Recent evidence indicates that EVs carry on their surface, specific molecules which bind to extracellular Aβ, opening the possibility that EVs may also influence Aβ assembly and synaptotoxicity. In this review we focus on studies which investigated the impact of EVs in Aβ-mediated neurodegeneration and showed either detrimental or protective role for EVs in the pathology. Full article

(This article belongs to the Special Issue Molecular Research in Neurotoxicology)

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24 pages, 1911 KiB

Open AccessReview

Chemical Structure, Property and Potential Applications of Biosurfactants Produced by Bacillus subtilis in Petroleum Recovery and Spill Mitigation

by Jin-Feng Liu^1,3, Serge Maurice Mbadinga^1,3

, Shi-Zhong Yang^1,3, Ji-Dong Gu² and Bo-Zhong Mu^1,3,*

¹ State Key Laboratory of Bioreactor Engineering and Institute of Applied Chemistry, East China University of Science and Technology, Shanghai 200237, China

² School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China

³ Shanghai Collaborative Innovation Center for Biomanufacturing Technology, Shanghai 200237, China

Int. J. Mol. Sci. 2015, 16(3), 4814-4837; https://doi.org/10.3390/ijms16034814 - 3 Mar 2015

Cited by 135 | Viewed by 11665

Abstract

Lipopeptides produced by microorganisms are one of the five major classes of biosurfactants known and they have received much attention from scientific and industrial communities due to their powerful interfacial and biological activities as well as environmentally friendly characteristics. Microbially produced lipopeptides are [...] Read more.

Lipopeptides produced by microorganisms are one of the five major classes of biosurfactants known and they have received much attention from scientific and industrial communities due to their powerful interfacial and biological activities as well as environmentally friendly characteristics. Microbially produced lipopeptides are a series of chemical structural analogues of different families and, among them, 26 families covering about 90 lipopeptide compounds have been reported in the last two decades. This paper reviews the chemical structural characteristics and molecular behaviors of surfactin, one of the representative lipopeptides of the 26 families. In particular, two novel surfactin molecules isolated from cell-free cultures of Bacillus subtilis HSO121 are presented. Surfactins exhibit strong self-assembly ability to form sphere-like micelles and larger aggregates at very low concentrations. The amphipathic and surface properties of surfactins are related to the existence of the minor polar and major hydrophobic domains in the three 3-D conformations. In addition, the application potential of surfactin in bioremediation of oil spills and oil contaminants, and microbial enhanced oil recovery are discussed. Full article

(This article belongs to the Special Issue Microbial Metabolism of Toxic Organic Pollutants and Transformation of Metals/Metalloids and Ecotoxicity Assessment)

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12 pages, 2972 KiB

Open AccessArticle

Nanoparticles of Copper Stimulate Angiogenesis at Systemic and Molecular Level

by Natalia Mroczek-Sosnowska¹, Ewa Sawosz², Krishna Prasad Vadalasetty³, Monika Łukasiewicz¹, Jan Niemiec¹, Mateusz Wierzbicki², Marta Kutwin², Sławomir Jaworski² and André Chwalibog^3,*

¹ Division of Poultry Breeding, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, Poland

² Division of Nanobiotechnology, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, Poland

³ Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Groennegaardsvej 3, 1870 Frederiksberg, Denmark

Int. J. Mol. Sci. 2015, 16(3), 4838-4849; https://doi.org/10.3390/ijms16034838 - 3 Mar 2015

Cited by 97 | Viewed by 8046

Abstract

Copper is a key element affecting blood vessel growth and muscle development. However, the ions released from Cu salts are toxic. Given their specific physicochemical properties, nanoparticles of Cu (NanoCu) may have different bioactivity and affect the development of blood vessel and muscles [...] Read more.

Copper is a key element affecting blood vessel growth and muscle development. However, the ions released from Cu salts are toxic. Given their specific physicochemical properties, nanoparticles of Cu (NanoCu) may have different bioactivity and affect the development of blood vessel and muscles in a different manner than Cu salts. The objective of the study was to evaluate the influence of NanoCu on embryo development and angiogenesis at the systemic and molecular level, in experiments using a chick embryo model. Fertilized chicken eggs were divided into a control group, and groups injected with a placebo, CuSO₄ or NanoCu. Embryo development at the whole body level and molecular indices using an embryo chorioallantoic membrane model were measured during embryogenesis. The present study indicated for the first time that NanoCu have pro-angiogenic properties at the systemic level, to a greater degree than CuSO₄ salt. The properties of NanoCu were confirmed at the molecular level, demonstrating significant effects on mRNA concentration and on mRNA gene expression of all pro-angiogenic and pro-proliferative genes measured herein. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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15 pages, 2912 KiB

Open AccessArticle

Expression of IL-8, IL-6 and IL-1β in Tears as a Main Characteristic of the Immune Response in Human Microbial Keratitis

by Concepcion Santacruz¹, Marisela Linares¹, Yonathan Garfias², Luisa M. Loustaunau¹, Lenin Pavon³

, Sonia Mayra Perez-Tapia⁴ and Maria C. Jimenez-Martinez^1,2,*

¹ Cornea and Refractive Surgery Department, and Research Unit, Institute of Ophthalmology "Conde de Valenciana Foundation", Mexico 06800, DF, Mexico

² Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, P.O. Box 70159, Mexico 04510, DF, Mexico

³ Department of Psychoimmunology, National Institute of Psychiatry "Ramón de la Fuente", Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Mexico City 14370, DF, Mexico

⁴ Unit of R&D in Bioprocesses (UDIBI), Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, Mexico 11340, DF, Mexico

Int. J. Mol. Sci. 2015, 16(3), 4850-4864; https://doi.org/10.3390/ijms16034850 - 3 Mar 2015

Cited by 45 | Viewed by 12395

Abstract

Corneal infections are frequent and potentially vision-threatening diseases, and despite the significance of the immunological response in animal models of microbial keratitis (MK), it remains unclear in humans. The aim of this study was to describe the cytokine profile of tears in patients [...] Read more.

Corneal infections are frequent and potentially vision-threatening diseases, and despite the significance of the immunological response in animal models of microbial keratitis (MK), it remains unclear in humans. The aim of this study was to describe the cytokine profile of tears in patients with MK. Characteristics of ocular lesions such as size of the epithelial defect, stromal infiltration, and hypopyon were analyzed. Immunological evaluation included determination of interleukine (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α in tear samples obtained from infected eyes of 28 patients with MK and compared with their contralateral non-infected eyes. Additionally, frequency of CD4⁺, CD8⁺, CD19⁺ and CD3⁻CD56⁺ cells was also determined in peripheral blood mononuclear cells in patients with MK, and compared with 48 healthy controls. Non-significant differences were observed in the size of the epithelial defect, stromal infiltration, and hypopyon. Nevertheless, we found an immunological profile apparently related to MK etiology. IL-8 > IL-6 in patients with bacterial keratitis; IL-8 > IL-6 > IL-1β and increased frequency of circulating CD3⁻CD56⁺ NK cells in patients with gram-negative keratitis; and IL-8 = IL-6 > IL-1β in patients with fungal keratitis. Characterization of tear cytokines from patients with MK could aid our understanding of the immune pathophysiological mechanisms underlying corneal damage in humans. Full article

(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)

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15 pages, 2388 KiB

Open AccessArticle

Biochemical Properties and Structure Analysis of a DAG-Like Lipase from Malassezia globosa

by Huan Xu^1,†, Dongming Lan^1,†, Bo Yang² and Yonghua Wang^1,*

¹ College of Light Industry and Food Sciences, South China University of Technology, Guangzhou 510640, China

² School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 4865-4879; https://doi.org/10.3390/ijms16034865 - 4 Mar 2015

Cited by 19 | Viewed by 8149

Abstract

Diacylglycerol (DAG)-like lipases are found to play an important role in the life sciences and industrial fields. A putative DAG-like lipase (MgMDL2) from Malassezia globosa was cloned and expressed in recombinant Pichia pastoris. The recombinant MgMDL2 was expressed as [...] Read more.

Diacylglycerol (DAG)-like lipases are found to play an important role in the life sciences and industrial fields. A putative DAG-like lipase (MgMDL2) from Malassezia globosa was cloned and expressed in recombinant Pichia pastoris. The recombinant MgMDL2 was expressed as a glycosylated protein and purified into homogeneity by anion exchange chromatography. The activity of recombinant MgMDL2 was optimal at 15 °C and pH 6.0, and it keeps over 50% of relative activity at 5 °C, suggesting that MgMDL2 was a cold active lipase. MgMDL2 retained over 80% of initial activity after incubation at 30 and 40 °C for 2.5 h, but it was not stable at 50 °C. Incubation of methanol and ethanol at a concentration of 30% for 2 h did not affect the recombinant enzyme activity, while metal ions, including Ca²⁺, Mn²⁺ and Ni²⁺, sharply inhibited the MgMDL2 activity at 5 mM by 42%, 35% and 36%, respectively. MgMDL2 exhibited a preference for medium chain-length esters with highest activity toward p-nitrophenyl caprylate, while it was active on mono- and diacylglycerol but not on triacylglycerol, indicating that it was a typical DAG-like lipase. By homology modeling, Phe278 was predicted to be involved in the preference of MgMDL2 for monoacyl- and diacyl-glyceride substrates, but not triglycerides. Full article

(This article belongs to the Collection Computational, Structural and Spectroscopic Studies of Enzyme Mechanisms, Inhibition and Dynamics)

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24 pages, 1425 KiB

Open AccessReview

Silk Fibroin-Based Nanoparticles for Drug Delivery

by Zheng Zhao^1,2,3, Yi Li^2,* and Mao-Bin Xie²

¹ State Key Lab of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China

² Institute of Textiles and Clothing, the Hong Kong Polytechnic University, Hong Kong 999077, China

³ Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China

Int. J. Mol. Sci. 2015, 16(3), 4880-4903; https://doi.org/10.3390/ijms16034880 - 4 Mar 2015

Cited by 287 | Viewed by 21310

Abstract

Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By [...] Read more.

Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By adjusting the particle size, the chemical structure and properties, the modified or recombinant SF-based nanoparticles can be designed to improve the therapeutic efficiency of drugs encapsulated into these nanoparticles. Therefore, they can be used to deliver small molecule drugs (e.g., anti-cancer drugs), protein and growth factor drugs, gene drugs, etc. This paper reviews recent progress on SF-based nanoparticles, including chemical structure, properties, and preparation methods. In addition, the applications of SF-based nanoparticles as carriers for therapeutic drugs are also reviewed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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14 pages, 1811 KiB

Open AccessArticle

Secretion of Human Protein C in Mouse Milk

by Chae-Won Park¹, Myung-Hwa Kang² and Kwan-Sik Min^1,*

¹ Animal Biotechnology, Graduate School of Bio and Information Technology, Institute of Genetic Engineering, Hankyong National University, Ansung 456-749, Korea

² Department of Food and Nutrition, Hoseo University, Asan 336-795, Korea

Int. J. Mol. Sci. 2015, 16(3), 4904-4917; https://doi.org/10.3390/ijms16034904 - 4 Mar 2015

Cited by 3 | Viewed by 5989

Abstract

To determine the production of recombinant human protein C (rec-hPC) in milk, we created two homozygous mice lines for the goat β-casein/hPC transgene. Females and males of both lines (#10 and #11) displayed normal growth, fertility, and lactated normally. The copy number of [...] Read more.

To determine the production of recombinant human protein C (rec-hPC) in milk, we created two homozygous mice lines for the goat β-casein/hPC transgene. Females and males of both lines (#10 and #11) displayed normal growth, fertility, and lactated normally. The copy number of the transgene was about fivefold higher in #10 line as compared to #11 line. mRNA expression of the transgene was only detected in the mammary glands of both lines. Furthermore, mRNA expression was fourfold higher on day 7 than on day 1 during lactation. Northern blot analysis of mRNA expression in the #10 line of transgenic (Tg) mice indicated a strong expression of the transgene in the mammary glands after seven days of lactation. Comparison of rec-hPC protein level with that of mRNA in the mammary glands showed a very similar pattern. A 52-kDa band corresponding to the hPC protein was strongly detected in mammary glands of the #10 line during lactation. We also detected two bands of heavy chain and one weak band of light chain in the milk of the #10 and #11 lines. One single band at 52 kDa was detected from CHO cells transfected with hPC cDNA. hPC was mainly localized in the alveolar epithelial cell of the mammary glands. The protein is strongly expressed in the cytoplasm of the cultured mammary gland tissue. hPC protein produced in milk ranged from 2 to 28 ng/mL. These experiments indicated that rec-hPC can be produced at high levels in mice mammary glands. Full article

(This article belongs to the Section Biochemistry)

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29 pages, 1745 KiB

Open AccessReview

Cancer Stratification by Molecular Imaging

by Justus Weber, Uwe Haberkorn and Walter Mier^*

Heidelberg University Hospital, Department of Nuclear Medicine, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany

Int. J. Mol. Sci. 2015, 16(3), 4918-4946; https://doi.org/10.3390/ijms16034918 - 4 Mar 2015

Cited by 24 | Viewed by 12089

Abstract

The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor [...] Read more.

The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2). Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter), as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers. Full article

(This article belongs to the Special Issue Molecular Classification of Human Cancer and Its Role in Tailored Cancer Therapy)

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26 pages, 2020 KiB

Open AccessReview

Monitoring the Spatiotemporal Activities of miRNAs in Small Animal Models Using Molecular Imaging Modalities

by Patrick Baril^*, Safia Ezzine and Chantal Pichon

Centre de Biophysique Moléculaire, CNRS UPR4301, Université d'Orléans, 45071 Orléans, France

Int. J. Mol. Sci. 2015, 16(3), 4947-4972; https://doi.org/10.3390/ijms16034947 - 4 Mar 2015

Cited by 16 | Viewed by 8324

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by binding mRNA targets via sequence complementary inducing translational repression and/or mRNA degradation. A current challenge in the field of miRNA biology is to understand the functionality of miRNAs under [...] Read more.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by binding mRNA targets via sequence complementary inducing translational repression and/or mRNA degradation. A current challenge in the field of miRNA biology is to understand the functionality of miRNAs under physiopathological conditions. Recent evidence indicates that miRNA expression is more complex than simple regulation at the transcriptional level. MiRNAs undergo complex post-transcriptional regulations such miRNA processing, editing, accumulation and re-cycling within P-bodies. They are dynamically regulated and have a well-orchestrated spatiotemporal localization pattern. Real-time and spatio-temporal analyses of miRNA expression are difficult to evaluate and often underestimated. Therefore, important information connecting miRNA expression and function can be lost. Conventional miRNA profiling methods such as Northern blot, real-time PCR, microarray, in situ hybridization and deep sequencing continue to contribute to our knowledge of miRNA biology. However, these methods can seldom shed light on the spatiotemporal organization and function of miRNAs in real-time. Non-invasive molecular imaging methods have the potential to address these issues and are thus attracting increasing attention. This paper reviews the state-of-the-art of methods used to detect miRNAs and discusses their contribution in the emerging field of miRNA biology and therapy. Full article

(This article belongs to the Collection Regulation by Non-coding RNAs)

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12 pages, 672 KiB

Open AccessReview

Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

by Nicholas Caffes¹, David B. Kurland¹, Volodymyr Gerzanich¹ and J. Marc Simard^1,2,3,*

¹ Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA

² Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

³ Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

Int. J. Mol. Sci. 2015, 16(3), 4973-4984; https://doi.org/10.3390/ijms16034973 - 4 Mar 2015

Cited by 69 | Viewed by 9510

Abstract

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell [...] Read more.

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial K_ATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke. Full article

(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)

12 pages, 797 KiB

Open AccessReview

Faldaprevir for the Treatment of Hepatitis C

by Tatsuo Kanda^1,*

, Osamu Yokosuka¹ and Masao Omata^2,3

¹ Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

² Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi 400-8506, Japan

³ University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

Int. J. Mol. Sci. 2015, 16(3), 4985-4996; https://doi.org/10.3390/ijms16034985 - 4 Mar 2015

Cited by 13 | Viewed by 6503

Abstract

The current treatments for chronic hepatitis C virus (HCV) genotype 1 infection are combinations of direct-acting antivirals, and faldaprevir is one of the new generation of HCV NS3/4A protease inhibitors. At the end of 2013, the US Food and Drug Administration (FDA) approved [...] Read more.

The current treatments for chronic hepatitis C virus (HCV) genotype 1 infection are combinations of direct-acting antivirals, and faldaprevir is one of the new generation of HCV NS3/4A protease inhibitors. At the end of 2013, the US Food and Drug Administration (FDA) approved the HCV NS3/4A protease inhibitor simeprevir and the HCV NS5B polymerase inhibitor sofosbuvir. Simeprevir or sofosbuvir in combination with pegylated interferon and ribavirin are available for clinical use. Faldaprevir, another HCV NS3/4A protease inhibitor that also has fewer adverse events than telaprevir or boceprevir, is under development. Of interest, faldaprevir in combination with pegylated interferon and ribavirin, and interferon-free treatment with faldaprevir in combination with deleobuvir plus ribavirin provides high sustained virological response rates for HCV genotype 1 infection. The aim of this article is to review these data concerning faldaprevir. Faldaprevir in combination with pegylated interferon and ribavirin treatment appears to be associated with fewer adverse events than telaprevir or boceprevir in combination with pegylated interferon and ribavirin, and may be one of the therapeutic options for treatment-naive patients with HCV genotype 1. The interferon-free combination of faldaprevir and deleobuvir with ribavirin was effective for HCV genotype 1 infection and may hold promise for interferon-ineligible and interferon-intolerant patients. Full article

(This article belongs to the Special Issue Viral Hepatitis Research)

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17 pages, 2566 KiB

Open AccessArticle

Transcriptome MicroRNA Profiling of Bovine Mammary Glands Infected with Staphylococcus aureus

by Rui Li^1,†, Cheng-Long Zhang^1,†, Xiang-Xiang Liao¹, Dan Chen¹, Wen-Qiang Wang¹, Yi-Hui Zhu¹, Xiao-Han Geng¹, De-Jun Ji¹, Yong-Jiang Mao¹, Yun-Chen Gong² and Zhang-Ping Yang^1,*

¹ College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China

² The Centre for the Analysis of Genome Evolution and Function (CAGEF), University of Toronto, Toronto, ON M5S 2J7, Canada

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 4997-5013; https://doi.org/10.3390/ijms16034997 - 4 Mar 2015

Cited by 86 | Viewed by 8899

Abstract

MicroRNAs are small non-coding RNA molecules that are important regulators of gene expression at the post-transcriptional level. miRNAs impact the processes of cell proliferation, differentiation and apoptosis. Thus, the regulation of miRNA expression profiles associated with mastitis will be conducive for its control. [...] Read more.

MicroRNAs are small non-coding RNA molecules that are important regulators of gene expression at the post-transcriptional level. miRNAs impact the processes of cell proliferation, differentiation and apoptosis. Thus, the regulation of miRNA expression profiles associated with mastitis will be conducive for its control. In this study, Staphylococcus aureus (S. aureus) was administered to the mammary gland of Chinese Holstein cows to construct a bacteria-type mastitis model. Total RNA was isolated from bovine mammary gland tissue samples from the S. aureus-induced mastitis group and controls. miRNAs were analyzed using Solexa sequencing and bioinformatics processing for the experimental group and control group. Two miRNA libraries were constructed respectively. A total of 370 known bovine miRNAs and 341 novel mi RNAs were detected for the S. aureus and 358 known bovine miRNAs and 232 novel miRNAs for control groups. A total of 77 miRNAs in the S. aureus group showed significant differences compared to the control group. GO (Gene Ontology) analysis showed these target genes were involved in the regulation of cells, binding, etc., while KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these genes were enriched in endocytosis, and olfactory transduction pathways involved in cancer. These results provide an experimental basis to reveal the cause and regulatory mechanism of mastitis and also suggest the potential of miRNAs to serve as biomarkers for the diagnosis of mastitis in dairy cows. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 1513 KiB

Open AccessArticle

Anticarcinogenic Properties of Medium Chain Fatty Acids on Human Colorectal, Skin and Breast Cancer Cells in Vitro

by Amoolya Narayanan¹, Sangeetha Ananda Baskaran², Mary Anne Roshni Amalaradjou²

and Kumar Venkitanarayanan^2,*

¹ Department of Psychology, University of Connecticut, 406 Babbidge Road, Unit 1020, Storrs, CT 06269-1020, USA

² Department of Animal Science, University of Connecticut, 3636 Horse Barn Hill Road Ext., Unit 4040, Storrs, CT 06269, USA

Int. J. Mol. Sci. 2015, 16(3), 5014-5027; https://doi.org/10.3390/ijms16035014 - 5 Mar 2015

Cited by 119 | Viewed by 9665

Abstract

Colorectal cancer, breast cancer and skin cancer are commonly-reported cancer types in the U.S. Although radiation and chemotherapy are routinely used to treat cancer, they produce side effects in patients. Additionally, resistance to chemotherapeutic drugs has been noticed in cancers. Thus, there is [...] Read more.

Colorectal cancer, breast cancer and skin cancer are commonly-reported cancer types in the U.S. Although radiation and chemotherapy are routinely used to treat cancer, they produce side effects in patients. Additionally, resistance to chemotherapeutic drugs has been noticed in cancers. Thus, there is a need for effective and safe bioprophylactics and biotherapeutics in cancer therapy. The medicinal value of goat milk has been recognized for centuries and is primarily attributed to three fatty acids, namely capric, caprylic and caproic acids. This research investigates the anticancer property of these fatty acids on human colorectal, skin and mammary gland cancer cells. The cancer cells were treated with various concentrations of fatty acids for 48 h, and cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Additionally, real-time quantitative PCR (RT-qPCR) was performed to elucidate the potential anti-cancer mechanisms of the three fatty acids under investigation. Capric, caprylic and caproic acids reduced cancer cell viability by 70% to 90% (p < 0.05) compared to controls. RT-qPCR data indicated that these natural molecules produced anticancer effects by down-regulating cell cycle regulatory genes and up-regulating genes involved in apoptosis. Future research will validate the anticancer effect of these fatty acids in an appropriate in vivo model. Full article

(This article belongs to the Section Biochemistry)

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19 pages, 1361 KiB

Open AccessArticle

Methemoglobin Is an Endogenous Toll-Like Receptor 4 Ligand—Relevance to Subarachnoid Hemorrhage

by Min Seong Kwon¹, Seung Kyoon Woo¹, David B. Kurland¹, Sung Hwan Yoon⁴, Andre F. Palmer⁵, Uddyalok Banerjee⁵, Sana Iqbal¹, Svetlana Ivanova¹, Volodymyr Gerzanich¹ and J. Marc Simard^1,2,3,*

¹ Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA

² Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

³ Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

⁴ Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA

⁵ William G. Lowrie Department of Chemical and Biomolecular Engineering, the Ohio State University, Columbus, OH 43210, USA

Int. J. Mol. Sci. 2015, 16(3), 5028-5046; https://doi.org/10.3390/ijms16035028 - 5 Mar 2015

Cited by 105 | Viewed by 9836

Abstract

Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and may be responsible for important complications of SAH. Signaling by Toll-like receptor 4 (TLR4)-mediated nuclear factor κB (NFκB) in microglia plays a critical role in neuronal damage after SAH. Three molecules derived from [...] Read more.

Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and may be responsible for important complications of SAH. Signaling by Toll-like receptor 4 (TLR4)-mediated nuclear factor κB (NFκB) in microglia plays a critical role in neuronal damage after SAH. Three molecules derived from erythrocyte breakdown have been postulated to be endogenous TLR4 ligands: methemoglobin (metHgb), heme and hemin. However, poor water solubility of heme and hemin, and lipopolysaccharide (LPS) contamination have confounded our understanding of these molecules as endogenous TLR4 ligands. We used a 5-step process to obtain highly purified LPS-free metHgb, as confirmed by Fourier Transform Ion Cyclotron Resonance mass spectrometry and by the Limulus amebocyte lysate assay. Using this preparation, we show that metHgb is a TLR4 ligand at physiologically relevant concentrations. metHgb caused time- and dose-dependent secretion of the proinflammatory cytokine, tumor necrosis factor α (TNFα), from microglial and macrophage cell lines, with secretion inhibited by siRNA directed against TLR4, by the TLR4-specific inhibitors, Rs-LPS and TAK-242, and by anti-CD14 antibodies. Injection of purified LPS-free metHgb into the rat subarachnoid space induced microglial activation and TNFα upregulation. Together, our findings support the hypothesis that, following SAH, metHgb in the subarachnoid space can promote widespread TLR4-mediated neuroinflammation. Full article

(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)

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25 pages, 911 KiB

Open AccessArticle

Identification and Pharmacokinetics of Multiple Potential Bioactive Constituents after Oral Administration of Radix Astragali on Cyclophosphamide-Induced Immunosuppression in Balb/c Mice

by Menghua Liu^1,2,*, Panlin Li³, Xuan Zeng³

, Huanxian Wu¹, Weiwei Su³ and Jingyu He^4,*

¹ Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China

² State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515, China

³ Guangzhou Quality R&D Center of Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China

⁴ Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, Guangdong, China

Int. J. Mol. Sci. 2015, 16(3), 5047-5071; https://doi.org/10.3390/ijms16035047 - 5 Mar 2015

Cited by 57 | Viewed by 8476

Abstract

Radix Astragali (RA) is one of the commonly-used traditional Chinese medicines (TCMs) with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic [...] Read more.

Radix Astragali (RA) is one of the commonly-used traditional Chinese medicines (TCMs) with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic profile after oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c mice. As a result, 51 compounds in RA extract and 31 prototype compounds with nine metabolites were detected in mice plasma by the ultra-fast liquid chromatography (UFLC)-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of five main constituents, including calycosin-7-O-glucoside, ononin, calycosin, formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results offered useful information for research on the pharmacological mechanism of RA and for its further development. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables)

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4 pages, 645 KiB

Open AccessCorrection

Correction: Xie, H.; et al. 3D QSAR Studies, Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors. Int. J. Mol. Sci. 2014, 15, 20927–20947

by Huiding Xie^1,2,*, Kaixiong Qiu² and Xiaoguang Xie^1,*

¹ Department of Chemistry, Yunnan University, Kunming 650091, Yunnan, China

² Department of Chemistry, School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, Yunnan, China

Int. J. Mol. Sci. 2015, 16(3), 5072-5075; https://doi.org/10.3390/ijms16035072 - 5 Mar 2015

Cited by 1 | Viewed by 4809

Abstract

A number of sentences in the first paragraph of the introduction of [28] were copied verbatim from [21,22,25,29]. Although [21,22,25] were cited in the text, [29] was omitted and it was not made sufficiently clear that direct quotations were used. The authors wish [...] Read more.

A number of sentences in the first paragraph of the introduction of [28] were copied verbatim from [21,22,25,29]. Although [21,22,25] were cited in the text, [29] was omitted and it was not made sufficiently clear that direct quotations were used. The authors wish to apologize to the authors of [21,22,25,29] and to the readers of the journal for any inconvenience.[...] Full article

49 pages, 3152 KiB

Open AccessReview

Ceramide-Induced Apoptosis in Renal Tubular Cells: A Role of Mitochondria and Sphingosine-1-Phoshate

by Norishi Ueda

Department of Pediatrics, Public Central Hospital of Matto Ishikawa, 3-8 Kuramitsu, Hakusan, Ishikawa 924-8588, Japan

Int. J. Mol. Sci. 2015, 16(3), 5076-5124; https://doi.org/10.3390/ijms16035076 - 5 Mar 2015

Cited by 77 | Viewed by 17885

Abstract

Ceramide is synthesized upon stimuli, and induces apoptosis in renal tubular cells (RTCs). Sphingosine-1 phosphate (S1P) functions as a survival factor. Thus, the balance of ceramide/S1P determines ceramide-induced apoptosis. Mitochondria play a key role for ceramide-induced apoptosis by altered mitochondrial outer membrane permeability [...] Read more.

Ceramide is synthesized upon stimuli, and induces apoptosis in renal tubular cells (RTCs). Sphingosine-1 phosphate (S1P) functions as a survival factor. Thus, the balance of ceramide/S1P determines ceramide-induced apoptosis. Mitochondria play a key role for ceramide-induced apoptosis by altered mitochondrial outer membrane permeability (MOMP). Ceramide enhances oligomerization of pro-apoptotic Bcl-2 family proteins, ceramide channel, and reduces anti-apoptotic Bcl-2 proteins in the MOM. This process alters MOMP, resulting in generation of reactive oxygen species (ROS), cytochrome C release into the cytosol, caspase activation, and apoptosis. Ceramide regulates apoptosis through mitogen-activated protein kinases (MAPKs)-dependent and -independent pathways. Conversely, MAPKs alter ceramide generation by regulating the enzymes involving ceramide metabolism, affecting ceramide-induced apoptosis. Crosstalk between Bcl-2 family proteins, ROS, and many signaling pathways regulates ceramide-induced apoptosis. Growth factors rescue ceramide-induced apoptosis by regulating the enzymes involving ceramide metabolism, S1P, and signaling pathways including MAPKs. This article reviews evidence supporting a role of ceramide for apoptosis and discusses a role of mitochondria, including MOMP, Bcl-2 family proteins, ROS, and signaling pathways, and crosstalk between these factors in the regulation of ceramide-induced apoptosis of RTCs. A balancing role between ceramide and S1P and the strategy for preventing ceramide-induced apoptosis by growth factors are also discussed. Full article

(This article belongs to the Collection Programmed Cell Death and Apoptosis)

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16 pages, 1191 KiB

Open AccessReview

An Epigenetic Regulator: Methyl-CpG-Binding Domain Protein 1 (MBD1)

by Lu Li^1,2,†, Bi-Feng Chen^2,3,† and Wai-Yee Chan^1,2,*

¹ The Chinese University of Hong Kong—Chinese Academy of Sciences Guangzhou Institute of Biomedicine and Health Joint Laboratory on Stem Cell and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

² The Chinese University of Hong Kong—Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

³ Department of Biological Science and Biotechnology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, Hubei, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5125-5140; https://doi.org/10.3390/ijms16035125 - 5 Mar 2015

Cited by 40 | Viewed by 11842

Abstract

DNA methylation is an important form of epigenetic regulation in both normal development and cancer. Methyl-CpG-binding domain protein 1 (MBD1) is highly related to DNA methylation. Its MBD domain recognizes and binds to methylated CpGs. This binding allows it to trigger methylation of [...] Read more.

DNA methylation is an important form of epigenetic regulation in both normal development and cancer. Methyl-CpG-binding domain protein 1 (MBD1) is highly related to DNA methylation. Its MBD domain recognizes and binds to methylated CpGs. This binding allows it to trigger methylation of H3K9 and results in transcriptional repression. The CXXC3 domain of MBD1 makes it a unique member of the MBD family due to its affinity to unmethylated DNA. MBD1 acts as an epigenetic regulator via different mechanisms, such as the formation of the MCAF1/MBD1/SETDB1 complex or the MBD1-HDAC3 complex. As methylation status always changes along with carcinogenesis or neurogenesis, MBD1 with its interacting partners, including proteins and non-coding RNAs, participates in normal or pathological processes and functions in different regulatory systems. Because of the important role of MBD1 in epigenetic regulation, it is a good candidate as a therapeutic target for diseases. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology 2014)

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20 pages, 14040 KiB

Open AccessArticle

The Infection Efficiency and Replication Ability of Circularized HBV DNA Optimized the Linear HBV DNA in Vitro and in Vivo

by Xiaosong Li¹, Junke Zhu¹, Guoqi Lai², Lei Yan², Jieli Hu¹, Juan Chen¹, Ni Tang^1,* and Ailong Huang¹

¹ Laboratory of Molecular Biology on Infectious Diseases and Institute for Viral Hepatitis, Ministry of Education, Chongqing Medical University, Chongqing 400016, China

² Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, China

Int. J. Mol. Sci. 2015, 16(3), 5141-5160; https://doi.org/10.3390/ijms16035141 - 5 Mar 2015

Cited by 4 | Viewed by 9476

Abstract

Studies on molecular mechanisms of the persist infection of hepatitis B virus have been hampered by a lack of a robust animal model. We successfully established a simple, versatile, and reproducible HBV persist infection model in vitro and in vivo with the circularized [...] Read more.

Studies on molecular mechanisms of the persist infection of hepatitis B virus have been hampered by a lack of a robust animal model. We successfully established a simple, versatile, and reproducible HBV persist infection model in vitro and in vivo with the circularized HBV DNA. The cells and mice were transfected or injected with circularized HBV DNA and pAAV/HBV1.2, respectively. At the indicated time, the cells, supernatants, serum samples, and liver tissues were collected for virological and serological detection. Both in vitro and in vivo, the circularized HBV DNA and pAAV/HBV1.2 could replicate and transcribe efficiently, but the infection effect of the former was superior to the latter (p < 0.05). The injection of circularized HBV genome DNA into the mice robustly supported HBV infection and approximately 80% of HBV infected mice established persistent infection for at least 10 weeks. This study demonstrated that the infection efficiency and replication ability of the circularized structure of HBV DNA overmatched that of the expression plasmid containing the linear structure of HBV DNA in vitro and in vivo. Meanwhile, this research results could provide useful tools and methodology for further study of pathogenic mechanisms and potential antiviral treatments of human chronic HBV infection in vitro and in vivo. Full article

(This article belongs to the Section Biochemistry)

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19 pages, 728 KiB

Open AccessReview

Potential Epigenetic Mechanism in Non-Alcoholic Fatty Liver Disease

by Chao Sun¹, Jian-Gao Fan^1,* and Liang Qiao^2,*

¹ Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China

² Storr Liver Centre, Westmead Millennium Institute for Medical Research, University of Sydney, the Westmead Clinical School, Westmead Hospital, Westmead, NSW 2145, Australia

Int. J. Mol. Sci. 2015, 16(3), 5161-5179; https://doi.org/10.3390/ijms16035161 - 5 Mar 2015

Cited by 82 | Viewed by 10793

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the liver. It ranges from simple steatosis to its more aggressive form, non-alcoholic steatohepatitis (NASH), which may develop into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC) if it persists for a [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the liver. It ranges from simple steatosis to its more aggressive form, non-alcoholic steatohepatitis (NASH), which may develop into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC) if it persists for a long time. However, the exact pathogenesis of NAFLD and the related metabolic disorders remain unclear. Epigenetic changes are stable alterations that take place at the transcriptional level without altering the underlying DNA sequence. DNA methylation, histone modifications and microRNA are among the most common forms of epigenetic modification. Epigenetic alterations are involved in the regulation of hepatic lipid metabolism, insulin resistance, mitochondrial damage, oxidative stress response, and the release of inflammatory cytokines, all of which have been implicated in the development and progression of NAFLD. This review summarizes the current advances in the potential epigenetic mechanism of NAFLD. Elucidation of epigenetic factors may facilitate the identification of early diagnositic biomarkers and development of therapeutic strategies for NAFLD. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)

14 pages, 2671 KiB

Open AccessArticle

Spectrofluorometric and Molecular Docking Studies on the Binding of Curcumenol and Curcumenone to Human Serum Albumin

by Omer Abdalla Ahmed Hamdi¹, Shevin Rizal Feroz², Jamil A. Shilpi³, El Hassane Anouar⁴

, Abdul Kadir Mukarram², Saharuddin B. Mohamad², Saad Tayyab² and Khalijah Awang^1,3,*

¹ Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

² Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia

³ Center of Natural products and Drug Discovery (CENAR), University of Malaya, 50603 Kuala Lumpur, Malaysia

⁴ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Malaysia

Int. J. Mol. Sci. 2015, 16(3), 5180-5193; https://doi.org/10.3390/ijms16035180 - 6 Mar 2015

Cited by 29 | Viewed by 6978

Abstract

Curcumenol and curcumenone are two major constituents of the plants of medicinally important genus of Curcuma, and often govern the pharmacological effect of these plant extracts. These two compounds, isolated from C. zedoaria rhizomes were studied for their binding to human serum [...] Read more.

Curcumenol and curcumenone are two major constituents of the plants of medicinally important genus of Curcuma, and often govern the pharmacological effect of these plant extracts. These two compounds, isolated from C. zedoaria rhizomes were studied for their binding to human serum albumin (HSA) using the fluorescence quench titration method. Molecular docking was also performed to get a more detailed insight into their interaction with HSA at the binding site. Additions of these sesquiterpenes to HSA produced significant fluorescence quenching and blue shifts in the emission spectra of HSA. Analysis of the fluorescence data pointed toward moderate binding affinity between the ligands and HSA, with curcumenone showing a relatively higher binding constant (2.46 × 10⁵ M⁻¹) in comparison to curcumenol (1.97 × 10⁴ M⁻¹). Cluster analyses revealed that site I is the preferred binding site for both molecules with a minimum binding energy of −6.77 kcal·mol⁻¹. However, binding of these two molecules to site II cannot be ruled out as the binding energies were found to be −5.72 and −5.74 kcal·mol⁻¹ for curcumenol and curcumenone, respectively. The interactions of both ligands with HSA involved hydrophobic interactions as well as hydrogen bonding. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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22 pages, 771 KiB

Open AccessReview

An Overview of the Prediction of Protein DNA-Binding Sites

by Jingna Si^*, Rui Zhao and Rongling Wu

Center for Computational Biology, National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China

Int. J. Mol. Sci. 2015, 16(3), 5194-5215; https://doi.org/10.3390/ijms16035194 - 6 Mar 2015

Cited by 82 | Viewed by 11626

Abstract

Interactions between proteins and DNA play an important role in many essential biological processes such as DNA replication, transcription, splicing, and repair. The identification of amino acid residues involved in DNA-binding sites is critical for understanding the mechanism of these biological activities. In [...] Read more.

Interactions between proteins and DNA play an important role in many essential biological processes such as DNA replication, transcription, splicing, and repair. The identification of amino acid residues involved in DNA-binding sites is critical for understanding the mechanism of these biological activities. In the last decade, numerous computational approaches have been developed to predict protein DNA-binding sites based on protein sequence and/or structural information, which play an important role in complementing experimental strategies. At this time, approaches can be divided into three categories: sequence-based DNA-binding site prediction, structure-based DNA-binding site prediction, and homology modeling and threading. In this article, we review existing research on computational methods to predict protein DNA-binding sites, which includes data sets, various residue sequence/structural features, machine learning methods for comparison and selection, evaluation methods, performance comparison of different tools, and future directions in protein DNA-binding site prediction. In particular, we detail the meta-analysis of protein DNA-binding sites. We also propose specific implications that are likely to result in novel prediction methods, increased performance, or practical applications. Full article

(This article belongs to the Special Issue Proteins and Protein-Ligand Interactions)

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19 pages, 4454 KiB

Open AccessArticle

Molecular Characterization and Functional Analysis of Three Pathogenesis-Related Cytochrome P450 Genes from Bursaphelenchus xylophilus (Tylenchida: Aphelenchoidoidea)

by Xiao-Lu Xu^1,2, Xiao-Qin Wu^1,2,*, Jian-Ren Ye^1,2 and Lin Huang^1,2

¹ Co-Innovation Center for Sustainable Forestry in Southern China, College of Forestry, Nanjing Forestry University, Nanjing 210037, China

² Jiangsu Key Laboratory for Prevention and Management of Invasive Species, Nanjing Forestry University, Nanjing 210037, China

Int. J. Mol. Sci. 2015, 16(3), 5216-5234; https://doi.org/10.3390/ijms16035216 - 6 Mar 2015

Cited by 39 | Viewed by 7339

Abstract

Bursaphelenchus xylophilus, the causal agent of pine wilt disease, causes huge economic losses in pine forests. The high expression of cytochrome P450 genes in B. xylophilus during infection in P. thunbergii indicated that these genes had a certain relationship with the pathogenic [...] Read more.

Bursaphelenchus xylophilus, the causal agent of pine wilt disease, causes huge economic losses in pine forests. The high expression of cytochrome P450 genes in B. xylophilus during infection in P. thunbergii indicated that these genes had a certain relationship with the pathogenic process of B. xylophilus. Thus, we attempted to identify the molecular characterization and functions of cytochrome P450 genes in B. xylophilus. In this study, full-length cDNA of three cytochrome P450 genes, BxCYP33C9, BxCYP33C4 and BxCYP33D3 were first cloned from B. xylophilus using 3' and 5' RACE PCR amplification. Sequence analysis showed that all of them contained a highly-conserved cytochrome P450 domain. The characteristics of the three putative proteins were analyzed with bioinformatic methods. RNA interference (RNAi) was used to assess the functions of BxCYP33C9, BxCYP33C4 and BxCYP33D3. The results revealed that these cytochrome P450 genes were likely to be associated with the vitality, dispersal ability, reproduction, pathogenicity and pesticide metabolism of B. xylophilus. This discovery confirmed the molecular characterization and functions of three cytochrome P450 genes from B. xylophilus and provided fundamental information in elucidating the molecular interaction mechanism between B. xylophilus and its host plant. Full article

(This article belongs to the Special Issue Plant Microbe Interaction)

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19 pages, 1075 KiB

Open AccessArticle

Hologram QSAR Models of a Series of 6-Arylquinazolin-4-Amine Inhibitors of a New Alzheimer’s Disease Target: Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase-1A Enzyme

by Felipe Dias Leal^1,*, Camilo Henrique Da Silva Lima¹

, Ricardo Bicca De Alencastro¹, Helena Carla Castro², Carlos Rangel Rodrigues³ and Magaly Girão Albuquerque^1,*

¹ Instituto de Química, Laboratório de Modelagem Molecular (LabMMol), Universidade Federal do Rio de Janeiro (UFRJ), 21949-900 Rio de Janeiro, RJ, Brazil

² Instituto de Biologia, Laboratório de Antibióticos, Bioquímica, Ensino e Modelagem Molecular (LABiEMol), Universidade Federal Fluminense (UFF), 24210-130 Niterói, RJ, Brazil

³ Faculdade de Farmácia, Laboratório de Modelagem Molecular & 3D-QSAR (ModMolQSAR), Universidade Federal do Rio de Janeiro (UFRJ), 21941-590 Rio de Janeiro, RJ, Brazil

Int. J. Mol. Sci. 2015, 16(3), 5235-5253; https://doi.org/10.3390/ijms16035235 - 6 Mar 2015

Cited by 12 | Viewed by 6258

Abstract

Dual specificity tyrosine-phosphorylation-regulated kinase-1A (DYRK1A) is an enzyme directly involved in Alzheimer’s disease, since its increased expression leads to β-amyloidosis, Tau protein aggregation, and subsequent formation of neurofibrillary tangles. Hologram quantitative structure-activity relationship (HQSAR, 2D fragment-based) models were developed for a series of [...] Read more.

Dual specificity tyrosine-phosphorylation-regulated kinase-1A (DYRK1A) is an enzyme directly involved in Alzheimer’s disease, since its increased expression leads to β-amyloidosis, Tau protein aggregation, and subsequent formation of neurofibrillary tangles. Hologram quantitative structure-activity relationship (HQSAR, 2D fragment-based) models were developed for a series of 6-arylquinazolin-4-amine inhibitors (36 training, 10 test) of DYRK1A. The best HQSAR model (q² = 0.757; SE_cv = 0.493; R² = 0.937; SE = 0.251; R²pred = 0.659) presents high goodness-of-fit (R² > 0.9), as well as high internal (q² > 0.7) and external (R²pred > 0.5) predictive power. The fragments that increase and decrease the biological activity values were addressed using the colored atomic contribution maps provided by the method. The HQSAR contribution map of the best model is an important tool to understand the activity profiles of new derivatives and may provide information for further design of novel DYRK1A inhibitors. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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17 pages, 956 KiB

Open AccessReview

Development of Small RNA Delivery Systems for Lung Cancer Therapy

by Yu Fujita^1,2, Kazuyoshi Kuwano² and Takahiro Ochiya^1,*

¹ Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo 104-0045, Japan

² Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan

Int. J. Mol. Sci. 2015, 16(3), 5254-5270; https://doi.org/10.3390/ijms16035254 - 6 Mar 2015

Cited by 53 | Viewed by 10069

Abstract

RNA interference (RNAi) has emerged as a powerful tool for studying target identification and holds promise for the development of therapeutic gene silencing. Recent advances in RNAi delivery and target selection provide remarkable opportunities for translational medical research. The induction of RNAi relies [...] Read more.

RNA interference (RNAi) has emerged as a powerful tool for studying target identification and holds promise for the development of therapeutic gene silencing. Recent advances in RNAi delivery and target selection provide remarkable opportunities for translational medical research. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications. Lung cancer is still the leading cause of cancer death worldwide, for which novel therapeutic strategies are critically needed. Recently, we have reported a novel platform (PnkRNA™ and nkRNA^®) to promote naked RNAi approaches through inhalation without delivery vehicles in lung cancer xenograft models. We suggest that a new class of RNAi therapeutic agent and local drug delivery system could also offer a promising RNAi-based strategy for clinical applications in cancer therapy. In this article, we show recent strategies for an RNAi delivery system and suggest the possible clinical usefulness of RNAi-based therapeutics for lung cancer treatment. Full article

(This article belongs to the Special Issue RNA Interference)

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14 pages, 1790 KiB

Open AccessArticle

Mechanistic Studies on the Dibenzofuran Formation from Phenanthrene, Fluorene and 9–Fluorenone

by Shanqing Li and Qingzhu Zhang^*

Environment Research Institute, Shandong University, Jinan 250100, China

Int. J. Mol. Sci. 2015, 16(3), 5271-5284; https://doi.org/10.3390/ijms16035271 - 6 Mar 2015

Cited by 7 | Viewed by 9002

Abstract

We carried out molecular orbital theory calculations for the homogeneous gas‑phase formation of dibenzofuran from phenanthrene, fluorene, 9-methylfluorene and 9-fluorenone. Dibenzofuran will be formed if ∙OH adds to C_8a, and the order of reactivity follows as 9-fluorenone > 9-methylfluorene > fluorene [...] Read more.

We carried out molecular orbital theory calculations for the homogeneous gas‑phase formation of dibenzofuran from phenanthrene, fluorene, 9-methylfluorene and 9-fluorenone. Dibenzofuran will be formed if ∙OH adds to C_8a, and the order of reactivity follows as 9-fluorenone > 9-methylfluorene > fluorene > phenanthrene. The oxidations initiated by ClO∙ are more favorable processes, considering that the standard reaction Gibbs energies are at least 21.63 kcal/mol lower than those of the equivalent reactions initiated by ∙OH. The adding of ∙OH and then O₂ to phenanthrene is a more favorable route than adding ∙OH to C_8a of phenanthrene, when considering the greater reaction extent. The reaction channel from fluorene and O₂ to 9-fluorenone and H₂O seems very important, not only because it contains only three elementary reactions, but because the standard reaction Gibbs energies are lower than −80.07 kcal/mol. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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14 pages, 2286 KiB

Open AccessArticle

Species-Dependent Splice Recognition of a Cryptic Exon Resulting from a Recurrent Intronic CEP290 Mutation that Causes Congenital Blindness

by Alejandro Garanto^1,2

, Lonneke Duijkers¹ and Rob W. J. Collin^1,2,*

¹ Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands

² Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands

Int. J. Mol. Sci. 2015, 16(3), 5285-5298; https://doi.org/10.3390/ijms16035285 - 9 Mar 2015

Cited by 26 | Viewed by 6075

Abstract

A mutation in intron 26 of CEP290 (c.2991+1655A>G) is the most common genetic cause of Leber congenital amaurosis (LCA), a severe type of inherited retinal degeneration. This mutation creates a cryptic splice donor site, resulting in the insertion of an aberrant exon (exon [...] Read more.

A mutation in intron 26 of CEP290 (c.2991+1655A>G) is the most common genetic cause of Leber congenital amaurosis (LCA), a severe type of inherited retinal degeneration. This mutation creates a cryptic splice donor site, resulting in the insertion of an aberrant exon (exon X) into ~50% of all CEP290 transcripts. A humanized mouse model with this mutation did not recapitulate the aberrant CEP290 splicing observed in LCA patients, suggesting differential recognition of cryptic splice sites between species. To further assess this phenomenon, we generated two CEP290 minigene constructs, with and without the intronic mutation, and transfected these in cell lines of various species. RT-PCR analysis revealed that exon X is well recognized by the splicing machinery in human and non-human primate cell lines. Intriguingly, this recognition decreases in cell lines derived from species such as dog and rodents, and it is completely absent in Drosophila. In addition, other cryptic splicing events corresponding to sequences in intron 26 of CEP290 were observed to varying degrees in the different cell lines. Together, these results highlight the complexity of splice site recognition among different species, and show that care is warranted when generating animal models to mimic splice site mutations in vivo. Full article

(This article belongs to the Special Issue Pre-mRNA Splicing 2015)

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35 pages, 3708 KiB

Open AccessArticle

Trans-Membrane Area Asymmetry Controls the Shape of Cellular Organelles

by Galina V. Beznoussenko^1,2, Sergei S. Pilyugin³, Willie J. C. Geerts⁴, Michael M. Kozlov⁵, Koert N. J. Burger⁴, Alberto Luini⁶, Jure Derganc^7,* and Alexander A. Mironov^1,2,*

¹ The FIRC Institute of Molecular Oncology, Milan 20139, Italy

² Consorzio Mario Negri Sud, S. Maria Imbaro, Chieti 66030, Italy

³ Department of Mathematics, University of Florida, Gainesville, FL 32611-8105, USA

⁴ Department of Biochemical Physiology, Institute of Biomembranes, 3584 CH Utrecht, The Netherlands

⁵ Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv 69978, Israel

⁶ Consiglio Nazionale delle Ricerche (CNR), Istituto di Biochimica delle Proteine, Naples 80131, Italy

⁷ Institute of Biophysics, University of Ljubljana, 1000 Ljubljana, Slovenia

Int. J. Mol. Sci. 2015, 16(3), 5299-5333; https://doi.org/10.3390/ijms16035299 - 9 Mar 2015

Cited by 14 | Viewed by 6653

Abstract

Membrane organelles often have complicated shapes and differ in their volume, surface area and membrane curvature. The ratio between the surface area of the cytosolic and luminal leaflets (trans-membrane area asymmetry (TAA)) determines the membrane curvature within different sites of the [...] Read more.

Membrane organelles often have complicated shapes and differ in their volume, surface area and membrane curvature. The ratio between the surface area of the cytosolic and luminal leaflets (trans-membrane area asymmetry (TAA)) determines the membrane curvature within different sites of the organelle. Thus, the shape of the organelle could be critically dependent on TAA. Here, using mathematical modeling and stereological measurements of TAA during fast transformation of organelle shapes, we present evidence that suggests that when organelle volume and surface area are constant, TAA can regulate transformation of the shape of the Golgi apparatus, endosomal multivesicular bodies, and microvilli of brush borders of kidney epithelial cells. Extraction of membrane curvature by small spheres, such as COPI-dependent vesicles within the Golgi (extraction of positive curvature), or by intraluminal vesicles within endosomes (extraction of negative curvature) controls the shape of these organelles. For instance, Golgi tubulation is critically dependent on the fusion of COPI vesicles with Golgi cisternae, and vice versa, for the extraction of membrane curvature into 50–60 nm vesicles, to induce transformation of Golgi tubules into cisternae. Also, formation of intraluminal ultra-small vesicles after fusion of endosomes allows equilibration of their TAA, volume and surface area. Finally, when microvilli of the brush border are broken into vesicles and microvilli fragments, TAA of these membranes remains the same as TAA of the microvilli. Thus, TAA has a significant role in transformation of organelle shape when other factors remain constant. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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13 pages, 1469 KiB

Open AccessArticle

Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies

by Luz Berenice López-Hernández^1,2,*,†

, Benjamín Gómez-Díaz³, Alexandra Berenice Luna-Angulo⁴, Mónica Anaya-Segura^2,5, David John Bunyan⁶, Carolina Zúñiga-Guzman^2,5, Rosa Elena Escobar-Cedillo³, Bladimir Roque-Ramírez¹, Luis Angel Ruano-Calderón⁷, Héctor Rangel-Villalobos⁸, Julia Angélica López-Hernández⁹, Francisco Javier Estrada-Mena⁴, Silvia García¹ and Ramón Mauricio Coral-Vázquez^10,†

¹ National Medical Centre "20 de Noviembre", Institute for Social Security of State Workers, Mexico City 03100, Mexico

² Asociación de Distrofia Muscular de Occidente A.C., Guadalajara 44380, Mexico

³ National Institute of Rehabilitation, Mexico City 14389, Mexico

⁴ Department of Molecular Biology, Panamerican University, Mexico City 03920, Mexico

⁵ University Center of Exact Sciences and Engineering, University of Guadalajara, Guadalajara 44430, Mexico

⁶ Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK

⁷ General Hospital of Durango, Durango, 34000, Mexico

⁸ Instituto de Investigación en Genética Molecular, Centro Universitario de la Ciénega, Universidad de Guadalajara, Ocotlán, 47810, México

⁹ Department of Human Genetics, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands

¹⁰ Studies Section of Postgraduate and Research, School of Medicine, National Polytechnic Institute, Mexico City 11340, Mexico

^† These authors contributed equally to this work.

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Int. J. Mol. Sci. 2015, 16(3), 5334-5346; https://doi.org/10.3390/ijms16035334 - 9 Mar 2015

Cited by 15 | Viewed by 9094

Abstract

Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation [...] Read more.

Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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16 pages, 1427 KiB

Open AccessArticle

A Perilipin Gene from Clonostachys rosea f. Catenulata HL-1-1 Is Related to Sclerotial Parasitism

by Zhan-Bin Sun

, Shi-Dong Li, Zeng-Ming Zhong and Man-Hong Sun^*

Key Laboratory of Integrated Pest Management in Crops, Ministry of Agriculture, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100081, China

Int. J. Mol. Sci. 2015, 16(3), 5347-5362; https://doi.org/10.3390/ijms16035347 - 9 Mar 2015

Cited by 9 | Viewed by 6362

Abstract

Clonostachys rosea f. catenulata is a promising biocontrol agent against many fungal plant pathogens. To identify mycoparasitism-related genes from C. rosea f. catenulata, a suppression subtractive hybridization (SSH) cDNA library of C. rosea f. catenulata HL-1-1 that parasitizes the sclerotia of S. [...] Read more.

Clonostachys rosea f. catenulata is a promising biocontrol agent against many fungal plant pathogens. To identify mycoparasitism-related genes from C. rosea f. catenulata, a suppression subtractive hybridization (SSH) cDNA library of C. rosea f. catenulata HL-1-1 that parasitizes the sclerotia of S. sclerotiorum was constructed. 502 clones were sequenced randomly, and thereby 472 expressed sequence tags (ESTs) were identified. Forty-three unigenes were annotated and exhibited similarity to a wide diversity of genes. Quantitative real -time PCR showed that a perilipin-like protein encoding gene, Per3, was up-regulated by 6.6-fold over the control at 96 h under the induction of sclerotia. The full-length sequence of Per3 was obtained via 5' and 3' rapid identification of cDNA ends. Overexpression of Per3 in HL-1-1 significantly enhanced the parasitic ability on sclerotia. The results indicated that Per3 might be involved in the mycoparasitism of C. rosea f. catenulata HL-1-1. This is the first report of a perilipin as a potential biocontrol gene in mycoparasites. The study provides usefu l insights into the interaction between C. rosea f. catenulata and fungal plant pathogens. Full article

(This article belongs to the Section Biochemistry)

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12 pages, 1729 KiB

Open AccessArticle

Tetraspanin 8-Rictor-Integrin α3 Complex Is Required for Glioma Cell Migration

by Si-Jian Pan^1,†, Shi-Kun Zhan^2,†, Yi-Xin Pan², Wei Liu², Liu-Guan Bian¹, Bomin Sun² and Qing-Fang Sun^1,*

¹ Department of Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China

² Department of Stereotactic and Functional Neurosurgery, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Shanghai Ruijin Second Road, Shanghai 200025, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5363-5374; https://doi.org/10.3390/ijms16035363 - 9 Mar 2015

Cited by 37 | Viewed by 6567

Abstract

The malignant glioma remains one of the most aggressive human malignancies with extremely poor prognosis. Glioma cell invasion and migration are the main causes of death. In the current study, we studied the expression and the potential functions of tetraspanin 8 (Tspan8) in [...] Read more.

The malignant glioma remains one of the most aggressive human malignancies with extremely poor prognosis. Glioma cell invasion and migration are the main causes of death. In the current study, we studied the expression and the potential functions of tetraspanin 8 (Tspan8) in malignant gliomas. We found that Tspan8 expression level is high in both malignant glioma tissues and in several human glioma cell lines, where it formed a complex integrin α3 and rictor, the latter is a key component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2). Disruption of this complex, through siRNA-mediated knockdown of anyone of these three proteins, inhibited U251MG glioma cell migration in vitro. We further showed that Tspan8-rictor association appeared required for mTORC2 activation. Knockdown of Tspan8 by the targeted siRNAs prevented mTOR-rictor (mTORC2) assembly as well as phosphorylation of AKT (Ser-473) and protein kinase C α (PKCα) in U251MG cells. Together, these results demonstrate that over-expressed Tspan8 in malignant glioma forms a complex with rictor and integrin α3 to mediate mTORC2 activation and glioma cell migration. Therefore, targeting Tspan8-rictor-integrin α3 complex may provide a potential therapeutic intervention for malignant glioma. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology)

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11 pages, 1544 KiB

Open AccessArticle

Monitoring of Apoptosis in 3D Cell Cultures by FRET and Light Sheet Fluorescence Microscopy

by Petra Weber¹, Sarah Schickinger¹, Michael Wagner¹, Brigitte Angres², Thomas Bruns¹ and Herbert Schneckenburger^1,*

¹ Institute of Applied Research, Aalen University, Anton-Huber Str. 21, 73430 Aalen, Germany

² Cellendes GmbH, Markwiesenstr. 55, 72770 Reutlingen, Germany

Int. J. Mol. Sci. 2015, 16(3), 5375-5385; https://doi.org/10.3390/ijms16035375 - 9 Mar 2015

Cited by 32 | Viewed by 10169

Abstract

Non-radiative cell membrane associated Förster Resonance Energy Transfer (FRET) from an enhanced cyan fluorescent protein (ECFP) to an enhanced yellow fluorescent protein (EYFP) is used for detection of apoptosis in 3-dimensional cell cultures. FRET is visualized in multi-cellular tumor spheroids by light sheet [...] Read more.

Non-radiative cell membrane associated Förster Resonance Energy Transfer (FRET) from an enhanced cyan fluorescent protein (ECFP) to an enhanced yellow fluorescent protein (EYFP) is used for detection of apoptosis in 3-dimensional cell cultures. FRET is visualized in multi-cellular tumor spheroids by light sheet based fluorescence microscopy in combination with microspectral analysis and fluorescence lifetime imaging (FLIM). Upon application of staurosporine and to some extent after treatment with phorbol-12-myristate-13-acetate (PMA), a specific activator of protein kinase c, the caspase-3 sensitive peptide linker DEVD is cleaved. This results in a reduction of acceptor (EYFP) fluorescence as well as a prolongation of the fluorescence lifetime of the donor (ECFP). Fluorescence spectra and lifetimes may, therefore, be used for monitoring of apoptosis in a realistic 3-dimensional system, while light sheet based microscopy appears appropriate for 3D imaging at low light exposure. Full article

(This article belongs to the Special Issue Förster Resonance Energy Transfer (FRET) 2015)

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14 pages, 1384 KiB

Open AccessArticle

Different Apoptotic Pathways Activated by Oxaliplatin in Primary Astrocytes vs. Colo-Rectal Cancer Cells

by Matteo Zanardelli¹, Laura Micheli¹, Raffaella Nicolai², Paola Failli¹, Carla Ghelardini¹ and Lorenzo Di Cesare Mannelli^1,*

¹ Department of Neuroscience, Psychology, Drug Research and Child Health – Neurofarba – Pharmacology and Toxicology Section, University of Florence, Florence 50139, Italy

² Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina km 30,400, I-00040 Pomezia, Rome 00040, Italy

Int. J. Mol. Sci. 2015, 16(3), 5386-5399; https://doi.org/10.3390/ijms16035386 - 9 Mar 2015

Cited by 20 | Viewed by 6090

Abstract

Oxaliplatin-based chemotherapy improves the outcomes of metastatic colorectal cancer patients. Its most significant and dose-limiting side effect is the development of a neuropathic syndrome. The mechanism of the neurotoxicity is unclear. The limited knowledge about differences existing between neurotoxic and antitumor effects hinders [...] Read more.

Oxaliplatin-based chemotherapy improves the outcomes of metastatic colorectal cancer patients. Its most significant and dose-limiting side effect is the development of a neuropathic syndrome. The mechanism of the neurotoxicity is unclear. The limited knowledge about differences existing between neurotoxic and antitumor effects hinders the discovery of effective and safe adjuvant therapies. In vitro, we suggested cell-specific activation apoptotic pathways in normal nervous cells (astrocytes) vs. colon-cancer cells (HT-29). In the present research we compared the apoptotic signals evoked by oxaliplatin in astrocytes and HT-29 analyzing the intrinsic and extrinsic apoptotic pathways. In astrocytes, oxaliplatin induced a mitochondrial derangement measured as cytosolic release of cytochrome C, increase in superoxide anion levels and decreased expression of the antiapoptotic protein Bcl-2. Caspase-8, a main initiator of the extrinsic process remained unaltered. On the contrary, in HT-29 oxaliplatin increased caspase-8 activity and Bid expression, thus activating the extrinsic apoptosis, while the Bcl-2 increased expression blocked the mitochondrial damage. Data suggest the preferred activation of the intrinsic apoptosis as oxaliplatin damage signaling in normal nervous cells. The extrinsic pathway prevails in tumor cells indicating a possible strategy for planning new molecules to treat oxaliplatin-dependent neurotoxicity without negatively influence chemotherapy. Full article

(This article belongs to the Section Biochemistry)

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20 pages, 4591 KiB

Open AccessReview

A Heme Oxygenase-1 Transducer Model of Degenerative and Developmental Brain Disorders

by Hyman M. Schipper^1,2,* and Wei Song¹

¹ Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T1E2, Canada

² Department of Neurology & Neurosurgery and Department of Medicine, McGill University and Jewish General Hospital, Montreal, QC H3T1E2, Canada

Int. J. Mol. Sci. 2015, 16(3), 5400-5419; https://doi.org/10.3390/ijms16035400 - 9 Mar 2015

Cited by 50 | Viewed by 8709

Abstract

Heme oxygenase-1 (HO-1) is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In [...] Read more.

Heme oxygenase-1 (HO-1) is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In “stressed” astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure documented in Alzheimer disease, Parkinson disease and certain neurodevelopmental conditions. Glial HO-1 expression may also impact neuroplasticity and cell survival by modulating brain sterol metabolism and the proteasomal degradation of neurotoxic proteins. The glial HO-1 response may represent a pivotal transducer of noxious environmental and endogenous stressors into patterns of neural damage and repair characteristic of many human degenerative and developmental CNS disorders. Full article

(This article belongs to the Special Issue Molecular Research in Neurotoxicology)

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14 pages, 3442 KiB

Open AccessArticle

MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter

by Lei Pan^1,2,3,4,†, Bi-Jun Huang^1,3,4,†, Xiu-E Ma^1,4,†, Shi-Yi Wang^1,4,†, Jing Feng^1,4, Fei Lv^1,4, Yuan Liu^1,4, Yi Liu^1,2,3, Chang-Ming Li^1,4, Dan-Dan Liang^1,2,3, Jun Li^1,2,3,4, Liang Xu^1,2,3,* and Yi-Han Chen^1,2,3,4,5,*

¹ Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

² Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

³ Institute of Medical Genetics, Tongji University, Shanghai 200092, China

⁴ Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

⁵ Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5420-5433; https://doi.org/10.3390/ijms16035420 - 10 Mar 2015

Cited by 80 | Viewed by 8062

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented [...] Read more.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H₂O₂, and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H₂O₂-induced elevation of mitochondrial Ca²⁺ concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes. Full article

(This article belongs to the Special Issue Pathogenesis of Cardiac Arrhythmias and Heart Failure)

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18 pages, 443 KiB

Open AccessArticle

SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients

by Mª Paz Zafra^1,2, Jose A. Cañas¹

, Carla Mazzeo^1,2, Cristina Gámez^1,2, Veronica Sanz^1,2, Mar Fernández-Nieto^2,3, Santiago Quirce^2,4, Pilar Barranco^2,4, Javier Ruiz-Hornillos⁵, Joaquín Sastre^2,3 and Victoria Del Pozo^1,2,*

¹ Department of Immunology, IIS-Fundación Jiménez Díaz, 28040 Madrid, Spain

² Centro de Investigación Biomedica En Red de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain

³ Department of Allergy, Fundación Jiménez Díaz, 28040 Madrid, Spain

⁴ Department of Allergy, Hospital La Paz Health Research Institute (IdiPAZ), 28046 Madrid, Spain

⁵ Department of Allergy, Hospital Infanta Elena, Valdemoro, 28342 Madrid, Spain

Int. J. Mol. Sci. 2015, 16(3), 5434-5451; https://doi.org/10.3390/ijms16035434 - 10 Mar 2015

Cited by 18 | Viewed by 6832

Abstract

Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor [...] Read more.

Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 688 KiB

Open AccessArticle

A Polymorphism at the Translation Start Site of the Vitamin D Receptor Gene Is Associated with the Response to Anti-Osteoporotic Therapy in Postmenopausal Women from Southern Italy

by Valeria Conti^1,†, Giusy Russomanno^2,†, Graziamaria Corbi^3,*

, Giuseppe Toro⁴, Vittorio Simeon⁵, Walter Filippelli⁶, Nicola Ferrara^7,8, Michela Grimaldi^1,‡, Valeria D'Argenio⁹

, Nicola Maffulli^10,11 and Amelia Filippelli¹

¹ Department of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy

² Doctoral School of Translational and Clinical Medicine, University of Salerno, Baronissi 84081, Italy

³ Department of Medicine and Health Sciences, University of Molise, Campobasso 86100, Italy

⁴ Unit of Orthopaedics and Traumatology, "Martiri del Villa Malta" Hospital, Sarno 84087, Italy

⁵ Laboratory of Pre-clinical and Translational Research, Reference Cancer Center of Basilicata, Scientific Institute of Hospitalization and Treatment, Rionero in Vulture 85028, Italy

⁶ Department of Studies for Institutions and Territorial Systems, University "Parthenope" of Naples, Naples 80133, Italy

⁷ Department of Medical Translational Sciences, University of Naples Federico II, Naples 80131, Italy

⁸ Maugeri Foundation, Scientific Institute of Telese, IRRCS, Telese Terme 82037, Italy

⁹ Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples 80131, Italy

¹⁰ Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Baronissi 84081, Italy

¹¹ Centre for Sports and Exercise Medicine, Barts and the London School of Medicine and Dentistry, Mile End Hospital, 275 Bancroft Road, London E1 4DG, UK

^† These authors contributed equally to this work.

^‡ This author is deceased during the study.

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Int. J. Mol. Sci. 2015, 16(3), 5452-5466; https://doi.org/10.3390/ijms16035452 - 10 Mar 2015

Cited by 93 | Viewed by 7080

Abstract

The present study investigated the effect of two single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in modulating bone mineral density (BMD) and the response to treatment with bisphosphonates or strontium ranelate in postmenopausal osteoporosis [...] Read more.

The present study investigated the effect of two single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in modulating bone mineral density (BMD) and the response to treatment with bisphosphonates or strontium ranelate in postmenopausal osteoporosis (PMO). Four hundred eighteen postmenopausal women from Southern Italy treated with bisphosphonates or strontium ranelate for three years were enrolled and stratified according to their genotype. Changes in BMD were expressed as the delta t-score (Δt-score). Allelic frequencies for rs1544410 A/GSNP were 11.2% AA, 50.0% GA and 38.8% GG; for rs2228570 C/TSNP were 54.8% CC, 39.5% TC and 5.7% TT. TT carriers showed a lower t-score than TC and CC (both p < 0.02) genotypes and were more responsive to the therapy when compared to both TC (p < 0.02) and CC (p < 0.05) carriers. Specifically, TT carriers receiving alendronate demonstrated a significant improvement of the Δt-score compared to TC and CC (both p < 0.0001) carriers. After adjustment for confounders, the Δt-score showed evidence of a statistically significant positive association with TT in all treatments considered. Therapy response was independent of rs1544410 A/G SNP; instead, rs2228570 C/TSNP was associated with a better response to antiresorptive treatment, thus suggesting that the therapy for PMO should be personalized. Full article

(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)

30 pages, 1688 KiB

Open AccessReview

Exploring the Secrets of Long Noncoding RNAs

by Mingyang Quan^1,2, Jinhui Chen^1,2 and Deqiang Zhang^1,2,*

¹ National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China

² Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, Ministry of Education, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China

Int. J. Mol. Sci. 2015, 16(3), 5467-5496; https://doi.org/10.3390/ijms16035467 - 10 Mar 2015

Cited by 117 | Viewed by 10663

Abstract

High-throughput sequencing has revealed that the majority of RNAs have no capacity to encode protein. Among these non-coding transcripts, recent work has focused on the roles of long noncoding RNAs (lncRNAs) of >200 nucleotides. Although many of their attributes, such as patterns of [...] Read more.

High-throughput sequencing has revealed that the majority of RNAs have no capacity to encode protein. Among these non-coding transcripts, recent work has focused on the roles of long noncoding RNAs (lncRNAs) of >200 nucleotides. Although many of their attributes, such as patterns of expression, remain largely unknown, lncRNAs have key functions in transcriptional, post-transcriptional, and epigenetic gene regulation; Also, new work indicates their functions in scaffolding ribonuclear protein complexes. In plants, genome-wide identification of lncRNAs has been conducted in several species, including Zea mays, and recent research showed that lncRNAs regulate flowering time in the photoperiod pathway, and function in nodulation. In this review, we discuss the basic mechanisms by which lncRNAs regulate key cellular processes, using the large body of knowledge on animal and yeast lncRNAs to illustrate the significance of emerging work on lncRNAs in plants. Full article

(This article belongs to the Collection Regulation by Non-coding RNAs)

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13 pages, 3315 KiB

Open AccessArticle

Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α

by Márcia Antoniazi Michelin^1,2, Letícia Montes¹, Rosekeila Simões Nomelini³, Marco Aurélio Trovó³ and Eddie Fernando Candido Murta^1,3,*

¹ Oncology Research Institute (IPON), Federal University of the TriânguloMineiro (UFTM), Uberaba, Minas Gerais 38022-200, Brazil

² Discipline of Immunology, UFTM, Uberaba, Minas Gerais 38022-200, Brazil

³ Discipline of Gynecology and Obstetrics, UFTM, Uberaba, Minas Gerais 38022-200, Brazil

Int. J. Mol. Sci. 2015, 16(3), 5497-5509; https://doi.org/10.3390/ijms16035497 - 10 Mar 2015

Cited by 7 | Viewed by 6033

Abstract

Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4⁺) [...] Read more.

Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4⁺) lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN). We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4⁺ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4⁺ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4⁺ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern. Full article

(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)

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7 pages, 698 KiB

Open AccessShort Communication

Impact of Soluble HLA-G Levels and Endometrial NK Cells in Uterine Flushing Samples from Primary and Secondary Unexplained Infertile Women

by Roberta Rizzo^1,†, Giuseppe Lo Monte^2,3,*,†, Daria Bortolotti¹, Angela Graziano^2,3, Valentina Gentili¹, Dario Di Luca¹ and Roberto Marci^2,3

¹ Department of Medical Sciences, Section of Microbiology and Genetics, University of Ferrara, 44100 Ferrara, Italy

² Department of Morphology, Surgery and Experimental Medicine, Section of Gynecology and Obstetrics, University of Ferrara, 44100 Ferrara, Italy

³ University Hospital "S. Anna", 44100 Ferrara, Italy

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5510-5516; https://doi.org/10.3390/ijms16035510 - 10 Mar 2015

Cited by 25 | Viewed by 6167

Abstract

The aim of this research was to determine the levels of human leukocyte antigen G (HLA-G) and endometrial Natural Killer ((e)NK) cell percentages in uterine flushing samples from primary and secondary infertile women. sHLA-G levels were lower in the uterine flushing samples from [...] Read more.

The aim of this research was to determine the levels of human leukocyte antigen G (HLA-G) and endometrial Natural Killer ((e)NK) cell percentages in uterine flushing samples from primary and secondary infertile women. sHLA-G levels were lower in the uterine flushing samples from primary infertile women in comparison with women with secondary infertility. Lower CD56⁺KIR2DL4⁺ (e)NK cell percentages were detected in primary infertile women compared with secondary infertile women. This is the first study demonstrating that primary and secondary unexplained infertilities are characterized by different basal sHLA-G levels and CD56⁺KIR2DL4⁺ (e)NK cell percentages. Full article

(This article belongs to the Special Issue Advances in Reproductive Biology)

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11 pages, 1118 KiB

Open AccessReview

Three-Dimensional Cell Culture: A Breakthrough in Vivo

by Delphine Antoni^1,2,*, Hélène Burckel², Elodie Josset² and Georges Noel^1,2

¹ Radiotherapy Department, Paul Strauss Cancer Center, 3, rue de la Porte de l'Hôpital, 67065 Strasbourg Cedex, France

² Radiobiology Laboratory, EA 3430, Strasbourg University, Paul Strauss Cancer Center, 3, rue de la Porte de l'Hôpital, 67065 Strasbourg Cedex, France

Int. J. Mol. Sci. 2015, 16(3), 5517-5527; https://doi.org/10.3390/ijms16035517 - 11 Mar 2015

Cited by 782 | Viewed by 30848

Abstract

Cell culture is an important tool for biological research. Two-dimensional cell culture has been used for some time now, but growing cells in flat layers on plastic surfaces does not accurately model the in vivo state. As compared to the two-dimensional case, the [...] Read more.

Cell culture is an important tool for biological research. Two-dimensional cell culture has been used for some time now, but growing cells in flat layers on plastic surfaces does not accurately model the in vivo state. As compared to the two-dimensional case, the three-dimensional (3D) cell culture allows biological cells to grow or interact with their surroundings in all three dimensions thanks to an artificial environment. Cells grown in a 3D model have proven to be more physiologically relevant and showed improvements in several studies of biological mechanisms like: cell number monitoring, viability, morphology, proliferation, differentiation, response to stimuli, migration and invasion of tumor cells into surrounding tissues, angiogenesis stimulation and immune system evasion, drug metabolism, gene expression and protein synthesis, general cell function and in vivo relevance. 3D culture models succeed thanks to technological advances, including materials science, cell biology and bioreactor design. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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27 pages, 3774 KiB

Open AccessReview

Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

by Adam Beach^†, Anna Leonov^†, Anthony Arlia-Ciommo^†, Veronika Svistkova^†, Vicky Lutchman^† and Vladimir I. Titorenko^*

¹ Department of Biology, Concordia University, 7141 Sherbrooke Street, West, SP Building, Room 501-13, Montreal, QC H4B 1R6, Canada

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5528-5554; https://doi.org/10.3390/ijms16035528 - 11 Mar 2015

Cited by 26 | Viewed by 10599

Abstract

Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a [...] Read more.

Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research. Full article

(This article belongs to the Section Biochemistry)

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17 pages, 920 KiB

Open AccessArticle

Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals

by Tzu-Yu Lin^1,4

, Cheng-Wei Lu^1,4

, Chia-Chan Wu¹, Shu-Kuei Huang¹ and Su-Jane Wang^2,3,*

¹ Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan

² Graduate Institute of Basic Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Distinct, New Taipei City 24205, Taiwan

³ School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Distinct, New Taipei City 24205, Taiwan

⁴ Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan

Int. J. Mol. Sci. 2015, 16(3), 5555-5571; https://doi.org/10.3390/ijms16035555 - 11 Mar 2015

Cited by 20 | Viewed by 5576

Abstract

The effect of palmitoylethanolamide (PEA), an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes) was investigated. PEA inhibited the Ca²⁺-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel [...] Read more.

The effect of palmitoylethanolamide (PEA), an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes) was investigated. PEA inhibited the Ca²⁺-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca²⁺ concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type) channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca²⁺ release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca²⁺ influx mediated by Cav2.1 (P/Q-type) channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway. Full article

(This article belongs to the Section Biochemistry)

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18 pages, 3356 KiB

Open AccessArticle

Regulatory Effects of Caffeic Acid Phenethyl Ester on Neuroinflammation in Microglial Cells

by Cheng-Fang Tsai^1,†, Yueh-Hsiung Kuo^1,2,†

, Wei-Lan Yeh³, Caren Yu-Ju Wu⁴, Hsiao-Yun Lin⁵, Sheng-Wei Lai⁴, Yu-Shu Liu⁴, Ling-Hsuan Wu⁴, Jheng-Kun Lu¹ and Dah-Yuu Lu^5,6,*

¹ Department of Biotechnology, Asia University, Taichung 413, Taiwan

² Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

³ Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua 500, Taiwan

⁴ Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung 404, Taiwan

⁵ Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 404, Taiwan

⁶ Department of Photonics and Communication Engineering, Asia University, Taichung 413, Taiwan

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5572-5589; https://doi.org/10.3390/ijms16035572 - 11 Mar 2015

Cited by 78 | Viewed by 8431

Abstract

Microglial activation has been widely demonstrated to mediate inflammatory processes that are crucial in several neurodegenerative disorders. Pharmaceuticals that can deliver direct inhibitory effects on microglia are therefore considered as a potential strategy to counter balance neurodegenerative progression. Caffeic acid phenethyl ester (CAPE), [...] Read more.

Microglial activation has been widely demonstrated to mediate inflammatory processes that are crucial in several neurodegenerative disorders. Pharmaceuticals that can deliver direct inhibitory effects on microglia are therefore considered as a potential strategy to counter balance neurodegenerative progression. Caffeic acid phenethyl ester (CAPE), a natural phenol in honeybee propolis, is known to possess antioxidant, anti-inflammatory and anti-microbial properties. Accordingly, the current study intended to probe the effects of CAPE on microglia activation by using in vitro and in vivo models. Western blot and Griess reaction assay revealed CAPE significantly inhibited the expressions of inducible nitric oxide synthase (NOS), cyclooxygenase (COX)-2 and the production of nitric oxide (NO). Administration of CAPE resulted in increased expressions of hemeoxygenase (HO)-1and erythropoietin (EPO) in microglia. The phosphorylated adenosine monophosphate-activated protein kinase (AMPK)-α was further found to regulate the anti-inflammatory effects of caffeic acid. In vivo results from immunohistochemistry along with rotarod test also revealed the anti-neuroinflammatory effects of CAPE in microglia activation. The current study has evidenced several possible molecular determinants, AMPKα, EPO, and HO-1, in mediating anti-neuroinflammatory responses in microglial cells. Full article

(This article belongs to the Special Issue Antioxidant 2.0——Redox Modulation by Food and Drugs)

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14 pages, 3207 KiB

Open AccessArticle

Extracellular Production of a Novel Endo-β-Agarase AgaA from Pseudomonas vesicularis MA103 that Cleaves Agarose into Neoagarotetraose and Neoagarohexaose

by Pang-Hung Hsu¹, Chien-Han Wei², Wen-Jung Lu², Fen Shen¹, Chorng-Liang Pan^2,* and Hong-Ting Victor Lin^2,3,*

¹ Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan

² Department of Food Science, National Taiwan Ocean University, Keelung 202, Taiwan

³ Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan

Int. J. Mol. Sci. 2015, 16(3), 5590-5603; https://doi.org/10.3390/ijms16035590 - 11 Mar 2015

Cited by 25 | Viewed by 6244

Abstract

The gene agaA, of the isolated marine bacterium Pseudomonas vesicularis MA103, comprised 2958-bp nucleotides encoding a putative agarase AgaA of 985 amino acids, which was predicted to contain a signal peptide of 29 amino acids in the N-terminus, a catalytic domain [...] Read more.

The gene agaA, of the isolated marine bacterium Pseudomonas vesicularis MA103, comprised 2958-bp nucleotides encoding a putative agarase AgaA of 985 amino acids, which was predicted to contain a signal peptide of 29 amino acids in the N-terminus, a catalytic domain of glycoside hydrolase 16 (GH16) family, a bacterial immunoglobulin group 2 (Big 2), and three carbohydrate binding modules 6 (CBM 6). The gene agaA was cloned and overexpressed in Escherichia coli, and the optimum temperatures for AgaA overexpression were 16, 20 and 24 °C. The agaA was cloned without its signal peptide for cytosolic production overexpression, whereas it was cloned with the heterologous signal peptide PelB and its endogenous signal peptide for periplasmic and extracellular productions, respectively. Extracellular and periplasmic rAgaA showed greater activity than that of cytosolic rAgaA, indicating that membrane translocation of AgaA may encourage proper protein folding. Time-course hydrolysis of agarose by rAgaA was accomplished and the products were analyzed using thin layer chromatography and matrix-assisted laser desorption inoization-time of flight mass spectrometry, indicating that AgaA from P. vesicularis was an endo-type β-1,4 agarase that cleaved agarose into neoagarotetraose and neoagarohexaose as the final products. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 895 KiB

Open AccessArticle

Effects of Ration Levels on Growth and Reproduction from Larvae to First-Time Spawning in the Female Gambusia affinis

by Zhiming Zhu, Xiangling Zeng, Xiaotao Lin^*, Zhongneng Xu and Jun Sun

Institute of Hydrobiology, Jinan University, Key Laboratory of Aquatic Eutrophication and Control of Harmful Algal Blooms of Guangdong Higher Education Institutes, 601 Huangpu Avenue West, Guangzhou 510632, China

Int. J. Mol. Sci. 2015, 16(3), 5604-5617; https://doi.org/10.3390/ijms16035604 - 11 Mar 2015

Cited by 4 | Viewed by 5564

Abstract

Somatic growth and reproduction were examined in individual laboratory-grown female Gambusia affinis fed with high (H), medium (M) and low (L) ration levels from birth to the first-time spawning. Results showed that the body length and weight, condition factor (CF), wet [...] Read more.

Somatic growth and reproduction were examined in individual laboratory-grown female Gambusia affinis fed with high (H), medium (M) and low (L) ration levels from birth to the first-time spawning. Results showed that the body length and weight, condition factor (CF), wet weight gain (WG_w), specific growth rate in wet weight (SGR_w) and ration levels in terms of energy (RL_e) decreased significantly (p < 0.05) with decreasing ration levels from birth to first-time spawning. On the contrary, the food conversion efficiency in terms of energy (FCE_e) increased significantly (p < 0.05) with the decreasing ration levels from birth to first-time sexual maturity. Furthermore, higher percentages of energy intake from food were allocated to somatic and gonad growth in M and L groups compared to the H group before sexual maturity; In addition, the time for first-time spawning in groups M and L was longer than that of the H group. As a result, the gonad-somatic index (GSI) and oocytes/embryos weight in M and L groups were similar to that of the H group, although the ovary weight and oocytes/embryos numbers were all lower than that of the H group. Also, similar growth performances were observed in second-generation offspring, which were produced by female parents fed with different ration levels. These findings suggest that the female G. affinis could produce a number of healthy offspring under conditions of food restriction, and that this could be achieved by increasing the energy allocated to gonad development, reducing fecundity and delaying spawning time. These life strategies ensured that G. affinis could survive and thrive in adverse environmental conditions and exhibit characteristics of invasive fish species. Full article

(This article belongs to the Special Issue Advances in Reproductive Biology)

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17 pages, 1991 KiB

Open AccessArticle

PEDF Improves Cardiac Function in Rats with Acute Myocardial Infarction via Inhibiting Vascular Permeability and Cardiomyocyte Apoptosis

by Hao Zhang^1,†, Zheng Wang^1,†, Shou-Jie Feng^1,†, Lei Xu¹, He-Xian Shi¹, Li-Li Chen¹, Guang-Da Yuan¹, Wei Yan¹, Wei Zhuang², Yi-Qian Zhang¹, Zhong-Ming Zhang^1,* and Hong-Yan Dong²

¹ Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China

² Research Facility Center for Morphology, Xuzhou Medical College, Xuzhou 221004, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5618-5634; https://doi.org/10.3390/ijms16035618 - 11 Mar 2015

Cited by 57 | Viewed by 8662

Abstract

Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury [...] Read more.

Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF’s effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size. Full article

(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)

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31 pages, 2327 KiB

Open AccessReview

Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

by Dianne Lorton^1,*,† and Denise L. Bellinger^2,†

¹ College of Arts and Sciences, Kent State University, Kent, OH 44304, USA

² Department of Human Anatomy and Pathology, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5635-5665; https://doi.org/10.3390/ijms16035635 - 11 Mar 2015

Cited by 172 | Viewed by 26060

Abstract

Cross-talk between the sympathetic nervous system (SNS) and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE) in lymphoid organs and tissues. NE stimulation of β₂ [...] Read more.

Cross-talk between the sympathetic nervous system (SNS) and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE) in lymphoid organs and tissues. NE stimulation of β₂-adrenergic receptors (ARs) in immune cells activates the cAMP-protein kinase A (PKA) intracellular signaling pathway, a pathway that interfaces with other signaling pathways that regulate proliferation, differentiation, maturation and effector functions in immune cells. Immune–SNS cross-talk is required to maintain homeostasis under normal conditions, to develop an immune response of appropriate magnitude after injury or immune challenge, and subsequently restore homeostasis. Typically, β₂-AR-induced cAMP is immunosuppressive. However, many studies report actions of β₂-AR stimulation in immune cells that are inconsistent with typical cAMP–PKA signal transduction. Research during the last decade in non-immune organs, has unveiled novel alternative signaling mechanisms induced by β₂-AR activation, such as a signaling switch from cAMP–PKA to mitogen-activated protein kinase (MAPK) pathways. If alternative signaling occurs in immune cells, it may explain inconsistent findings of sympathetic regulation of immune function. Here, we review β₂-AR signaling, assess the available evidence for alternative signaling in immune cells, and provide insight into the circumstances necessary for “signal switching” in immune cells. Full article

(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)

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16 pages, 3352 KiB

Open AccessArticle

Novel Cholesterol-Based Cationic Lipids as Transfecting Agents of DNA for Efficient Gene Delivery

by Jia Ju^†, Meng-Lei Huan^†, Ning Wan, Hai Qiu, Si-Yuan Zhou and Bang-Le Zhang^*

¹ Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5666-5681; https://doi.org/10.3390/ijms16035666 - 11 Mar 2015

Cited by 36 | Viewed by 8910

Abstract

The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-l-α-glycero-3-phosphatidyl-ethanolamine) exhibited [...] Read more.

The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-l-α-glycero-3-phosphatidyl-ethanolamine) exhibited good transfection efficiency. pEGFP-N₁ plasmid DNA was transferred into 293T cells by cationic liposomes formed from cationic lipids 1a and 1b, and the transfection activity of the cationic lipids was superior (1a) or parallel (1b) to that of the commercially available 3β-[N-(N',N'-dimethylaminoethyl)-carbamoyl] cholesterol (DC-Chol) derived from the same cholesterol backbone with different head groups. Combined with the results of agarose gel electrophoresis, transfection experiments with various molar ratios of the cationic lipids and DOPE and N/P (+/−) molar charge ratios, a more effective formulation was formed, which could lead to relatively high transfection efficiency. Cationic lipid 1a represents a potential agent for the liposome used in gene delivery due to low cytotoxicity and impressive gene transfection activity. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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15 pages, 1689 KiB

Open AccessReview

Coupling and Coordination in Gene Expression Processes with Pre-mRNA Splicing

by Kewu Pan, Jimmy Tsz Hang Lee, Zhe Huang and Chi-Ming Wong^*

State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine, Shenzhen Institute of Research and Innovation, The University of Hong Kong, L8-43, 21 Sassoon Road, Pokfulam, Hong Kong, China

Int. J. Mol. Sci. 2015, 16(3), 5682-5696; https://doi.org/10.3390/ijms16035682 - 11 Mar 2015

Cited by 6 | Viewed by 14925

Abstract

A processing is a tightly regulated and highly complex pathway which includes transcription, splicing, editing, transportation, translation and degradation. It has been well-documented that splicing of RNA polymerase II medicated nascent transcripts occurs co-transcriptionally and is functionally coupled to other RNA processing. Recently, [...] Read more.

A processing is a tightly regulated and highly complex pathway which includes transcription, splicing, editing, transportation, translation and degradation. It has been well-documented that splicing of RNA polymerase II medicated nascent transcripts occurs co-transcriptionally and is functionally coupled to other RNA processing. Recently, increasing experimental evidence indicated that pre-mRNA splicing influences RNA degradation and vice versa. In this review, we summarized the recent findings demonstrating the coupling of these two processes. In addition, we highlighted the importance of splicing in the production of intronic miRNA and circular RNAs, and hence the discovery of the novel mechanisms in the regulation of gene expression. Full article

(This article belongs to the Special Issue Pre-mRNA Splicing 2015)

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17 pages, 2854 KiB

Open AccessArticle

Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation

by Hee Jeong Yoo^1,2,†, Kyung Kim^3,4,7,†, In Hyang Kim¹, Seong-Hwan Rho⁵, Jong-Eun Park¹, Ki Young Lee^4,7,‡, Soon Ae Kim⁶, Byung Yoon Choi^2,8 and Namshin Kim^3,*

¹ Department of Psychiatry, Seoul National University Hospital, Seongnam, Gyeonggi 463-707, Korea

² Department of Psychiatry, Seoul National University, College of Medicine, Seoul 110-744, Korea

³ Epigenomics Research Center, Genome Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea

⁴ Department of Biomedical Informatics, Ajou University, School of Medicine, Suwon 443-749, Korea

⁵ Simulacre Modeling Group, Seoul 140-897, Korea

⁶ Department of Pharmacology, Eulji University College of Medicine, Daejeon 301-746, Korea

⁷ Department of Biomedical Science, Ajou University Graduate School of Medicine, Suwon 443-749, Korea

⁸ Department of Otolaryngology, Seoul National University Hospital, Seongnam, Gyeonggi 463-707, Korea

^† These authors contributed equally to this work.

^‡ Deceased.

Int. J. Mol. Sci. 2015, 16(3), 5697-5713; https://doi.org/10.3390/ijms16035697 - 11 Mar 2015

Cited by 10 | Viewed by 11519

Abstract

Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000–720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. [...] Read more.

Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000–720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes. Full article

(This article belongs to the Special Issue The Identification of the Genetic Components of Autism Spectrum Disorders)

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27 pages, 1359 KiB

Open AccessArticle

Genome-Wide Identification and Analysis of Drought-Responsive Genes and MicroRNAs in Tobacco

by Fuqiang Yin^1,2,†, Cheng Qin^2,3,†, Jian Gao^2,†, Ming Liu¹, Xirong Luo³, Wenyou Zhang¹, Hongjun Liu², Xinhui Liao⁴, Yaou Shen², Likai Mao⁴, Zhiming Zhang², Haijian Lin², Thomas Lübberstedt⁵ and Guangtang Pan^2,*

¹ School of Agricultural Sciences, Xichang College, Xichang 615000, China

² Maize Research Institute of Sichuan Agricultural University/Key Laboratory of Biology and Genetic Improvement of Maize in Southwest Region, Ministry of Agriculture, Chengdu 611130, China

³ Zunyi Academy of Agricultural Sciences, Zunyi 563102, China

⁴ Beijing Genomics Institute-Shenzhen, Shenzhen 518083, China

⁵ Department of Agronomy, Iowa State University, Ames, IA 50011, USA

^† These authors are equally contributed to this work.

Int. J. Mol. Sci. 2015, 16(3), 5714-5740; https://doi.org/10.3390/ijms16035714 - 12 Mar 2015

Cited by 33 | Viewed by 9516

Abstract

Drought stress response is a complex trait regulated at transcriptional and post-transcriptional levels in tobacco. Since the 1990s, many studies have shown that miRNAs act in many ways to regulate target expression in plant growth, development and stress response. The recent draft genome [...] Read more.

Drought stress response is a complex trait regulated at transcriptional and post-transcriptional levels in tobacco. Since the 1990s, many studies have shown that miRNAs act in many ways to regulate target expression in plant growth, development and stress response. The recent draft genome sequence of Nicotiana benthamiana has provided a framework for Digital Gene Expression (DGE) and small RNA sequencing to understand patterns of transcription in the context of plant response to environmental stress. We sequenced and analyzed three Digital Gene Expression (DGE) libraries from roots of normal and drought-stressed tobacco plants, and four small RNA populations from roots, stems and leaves of control or drought-treated tobacco plants, respectively. We identified 276 candidate drought responsive genes (DRGs) with sequence similarities to 64 known DRGs from other model plant crops, 82 were transcription factors (TFs) including WRKY, NAC, ERF and bZIP families. Of these tobacco DRGs, 54 differentially expressed DRGs included 21 TFs, which belonged to 4 TF families such as NAC (6), MYB (4), ERF (10), and bZIP (1). Additionally, we confirmed expression of 39 known miRNA families (122 members) and five conserved miRNA families, which showed differential regulation under drought stress. Targets of miRNAs were further surveyed based on a recently published study, of which ten targets were DRGs. An integrated gene regulatory network is proposed for the molecular mechanisms of tobacco root response to drought stress using differentially expressed DRGs, the changed expression profiles of miRNAs and their target transcripts. This network analysis serves as a reference for future studies on tobacco response stresses such as drought, cold and heavy metals. Full article

(This article belongs to the Special Issue Abiotic Stress and Gene Networks in Plants)

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9 pages, 736 KiB

Open AccessReview

The Importance of G Protein-Coupled Receptor Kinase 4 (GRK4) in Pathogenesis of Salt Sensitivity, Salt Sensitive Hypertension and Response to Antihypertensive Treatment

by Brian Rayner^1,* and Raj Ramesar²

¹ Division of Nephrology and Hypertension, University of Cape Town, Cape Town 7925, South Africa

² MRC Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa

Int. J. Mol. Sci. 2015, 16(3), 5741-5749; https://doi.org/10.3390/ijms16035741 - 12 Mar 2015

Cited by 25 | Viewed by 8499

Abstract

Salt sensitivity is probably caused by either a hereditary or acquired defect of salt excretion by the kidney, and it is reasonable to consider that this is the basis for differences in hypertension between black and white people. Dopamine acts in an autocrine/paracrine [...] Read more.

Salt sensitivity is probably caused by either a hereditary or acquired defect of salt excretion by the kidney, and it is reasonable to consider that this is the basis for differences in hypertension between black and white people. Dopamine acts in an autocrine/paracrine fashion to promote natriuresis in the proximal tubule and thick ascending loop of Henle. G-protein receptor kinases (or GRKs) are serine and threonine kinases that phosphorylate G protein-coupled receptors in response to agonist stimulation and uncouple the dopamine receptor from its G protein. This results in a desensitisation process that protects the cell from repeated agonist exposure. GRK4 activity is increased in spontaneously hypertensive rats, and infusion of GRK4 antisense oligonucleotides attenuates the increase in blood pressure (BP). This functional defect is replicated in the proximal tubule by expression of GRK4 variants namely p.Arg65Leu, p.Ala142Val and p.Val486Ala, in cell lines, with the p.Ala142Val showing the most activity. In humans, GRK4 polymorphisms were shown to be associated with essential hypertension in Australia, BP regulation in young adults, low renin hypertension in Japan and impaired stress-induced Na excretion in normotensive black men. In South Africa, GRK4 polymorphisms are more common in people of African descent, associated with impaired Na excretion in normotensive African people, and predict blood pressure response to Na restriction in African patients with mild to moderate essential hypertension. The therapeutic importance of the GRK4 single nucleotide polymorphisms (SNPs) was emphasised in the African American Study of Kidney Disease (AASK) where African-Americans with hypertensive nephrosclerosis were randomised to receive amlodipine, ramipril or metoprolol. Men with the p.Ala142Val genotype were less likely to respond to metoprolol, especially if they also had the p.Arg65Leu variant. Furthermore, in the analysis of response to treatment in two major hypertension studies, the 65Leu/142Val heterozygote predicted a significantly decreased response to atenolol treatment, and the 65Leu/142Val heterozygote and 486Val homozygote were associated in an additive fashion with adverse cardiovascular outcomes, independent of BP. In conclusion, there is considerable evidence that GRK4 variants are linked to impaired Na excretion, hypertension in animal models and humans, therapeutic response to dietary Na restriction and response to antihypertensive drugs. It may also underlie the difference in hypertension between different geographically derived population groups, and form a basis for pharmacogenomic approaches to treatment of hypertension. Full article

(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)

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12 pages, 1145 KiB

Open AccessArticle

Anti-TMV Activity of Malformin A₁, a Cyclic Penta-Peptide Produced by an Endophytic Fungus Aspergillus tubingensis FJBJ11

by Qing-Wei Tan^1,2, Fang-Luan Gao^1,2, Fu-Rong Wang¹ and Qi-Jian Chen^1,2,*

¹ Key Laboratory of Bio-pesticide and Chemistry-Biology, Ministry of Education, Fujian Agriculture and Forestry University, Fuzhou 350002, China

² Key Laboratory of Plant Virology of Fujian Province, Institute of Plant Virology, Fujian Agriculture and Forestry University, Fuzhou 350002, China

Int. J. Mol. Sci. 2015, 16(3), 5750-5761; https://doi.org/10.3390/ijms16035750 - 12 Mar 2015

Cited by 36 | Viewed by 8015

Abstract

Plant-associated microorganisms are known to produce a variety of metabolites with novel structures and interesting biological activities. An endophytic fungus FJBJ11, isolated from the plant tissue of Brucea javanica (L.) Merr. (Simaroubaceae), was proven to be significantly effective in producing metabolites with anti- [...] Read more.

Plant-associated microorganisms are known to produce a variety of metabolites with novel structures and interesting biological activities. An endophytic fungus FJBJ11, isolated from the plant tissue of Brucea javanica (L.) Merr. (Simaroubaceae), was proven to be significantly effective in producing metabolites with anti-Tobacco mosaic virus (TMV) activities. The isolate was identified as Aspergillus tubingensis FJBJ11 based on morphological characteristics and ITS sequence. Bioassay-guided isolation led to the identification of a cycli penta-peptide, malformin A₁, along with two cyclic dipeptides, cyclo (Gly-l-Pro) and cyclo (Ala-Leu). Malformin A₁ showed potent inhibitory effect against the infection and replication of TMV with IC₅₀ values of 19.7 and 45.4 μg·mL⁻¹, as tested using local lesion assay and leaf-disc method, respectively. The results indicated the potential use of malformin A₁ as a leading compound or a promising candidate of new viricide. Full article

(This article belongs to the Special Issue Bioactive Carbohydrates and Peptides)

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17 pages, 1065 KiB

Open AccessArticle

Phenolic Composition and Antioxidant Properties of Different Peach [Prunus persica (L.) Batsch] Cultivars in China

by Xiaoyong Zhao^1,2, Wenna Zhang^1,2, Xueren Yin^1,2,3, Mingshen Su⁴, Chongde Sun^1,2,3, Xian Li^1,2,3,* and Kunsong Chen^1,2,3

¹ Laboratory of Fruit Quality Biology, Zhejiang University, Zijingang Campus, Hangzhou 310058, Zhejiang, China

² The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Zijingang Campus, Hangzhou 310058, Zhejiang, China

³ Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Zijingang Campus, Hangzhou 310058, Zhejiang, China

⁴ Forestry and Pomology Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai 20l403, China

Int. J. Mol. Sci. 2015, 16(3), 5762-5778; https://doi.org/10.3390/ijms16035762 - 12 Mar 2015

Cited by 107 | Viewed by 10139

Abstract

China is an important centre of diversity for Prunus persica. In the present study, 17 Chinese peach cultivars were evaluated for phenolic content and antioxidant activity. Neochlorogenic acid (NCHA), chlorogenic acid (CHA), procyanidin B1 (B1), catechin (CAT), cyanidin-3-O-glucoside (C3G), quercetin-3- [...] Read more.

China is an important centre of diversity for Prunus persica. In the present study, 17 Chinese peach cultivars were evaluated for phenolic content and antioxidant activity. Neochlorogenic acid (NCHA), chlorogenic acid (CHA), procyanidin B1 (B1), catechin (CAT), cyanidin-3-O-glucoside (C3G), quercetin-3-O-galactoside (Q3GAL), quercetin-3-O-glucoside (Q3GLU), quercetin-3-O-rutinoside (Q3R), and kaempferol-3-O-rutinoside (K3R) were identified and quantified. CHA and CAT were the predominant components in both the peel and pulp of this fruit. In general, peel extracts showed higher antioxidant activities than the pulp counterparts, consistent with the observed higher phenolic content. The melting peach cultivar “Xinyu” showed the highest antioxidant potency composite (APC) index. The principal component analysis (PCA) of peel phenolics showed a clear distinction between the melting peach and nectarine. Overall, peach cultivars rich in hydroxycinnamates and flavan-3-ols showed relatively higher antioxidant activities and might be excellent sources of phytochemicals and natural antioxidants. Full article

(This article belongs to the Section Biochemistry)

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10 pages, 1680 KiB

Open AccessArticle

Biomechanical Evaluation of Ti-Nb-Sn Alloy Implants with a Low Young’s Modulus

by Kenta Takahashi¹, Naru Shiraishi^1,2,*, Risa Ishiko-Uzuka¹, Takahisa Anada³, Osamu Suzuki³, Hiroshi Masumoto⁴ and Keiichi Sasaki¹

¹ Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8577, Japan

² Division of Community Oral Health Science, Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8573, Japan

³ Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8577, Japan

⁴ Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Aramaki aza Aoba 6-3, Aoba-ku, Sendai 980-8578, Japan

Int. J. Mol. Sci. 2015, 16(3), 5779-5788; https://doi.org/10.3390/ijms16035779 - 12 Mar 2015

Cited by 18 | Viewed by 6044

Abstract

Dental implants are widely used and are a predictable treatment in various edentulous cases. Occlusal overload may be causally related to implant bone loss and a loss of integration. Stress concentrations may be diminished using a mechanobiologically integrated implant with bone tissue. The [...] Read more.

Dental implants are widely used and are a predictable treatment in various edentulous cases. Occlusal overload may be causally related to implant bone loss and a loss of integration. Stress concentrations may be diminished using a mechanobiologically integrated implant with bone tissue. The purpose of this study was to investigate the biomechanical behavior, biocompatibility and bioactivity of a Ti-Nb-Sn alloy as a dental implant material. It was compared with cpTi. Cell proliferation and alkaline phosphatase (ALP) activity were quantified. To assess the degree of osseointegration, a push-in test was carried out. Cell proliferation and ALP activity in the cells grown on prepared surfaces were similar for the Ti-Nb-Sn alloy and for cpTi in all the experiments. A comparison between the Ti-Nb-Sn alloy implant and the cpTi implant revealed that no significant difference was apparent for the push-in test values. These results suggest that implants fabricated using Ti-Nb-Sn have a similar biological potential as cpTi and are capable of excellent osseointegration. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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14 pages, 1299 KiB

Open AccessArticle

Protective Effects of Resveratrol against UVA-Induced Damage in ARPE19 Cells

by Chi-Ming Chan^1,2,†, Cheng-Hua Huang^1,3,†, Hsin-Ju Li⁴, Chien-Yu Hsiao^5,6, Ching-Chieh Su^1,7,8, Pei-Lan Lee⁹ and Chi-Feng Hung^1,*

¹ School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan

² Department of Ophthalmology, Cardinal Tien Hospital, Hsiendian, New Taipei City 23148, Taiwan

³ Department of Internal Medicine, Cathay General Hospital, Taipei 10630, Taiwan

⁴ Department of Chemstry, Fu Jen Catholic University, New Taipei City 24205, Taiwan

⁵ Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kweishan, Taoyuan 33303, Taiwan

⁶ Research center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan 33303, Taiwan

⁷ Graduate Institute of Applied Science and Engineering, Fu Jen Catholic University, New Taipei City 24205, Taiwan

⁸ Department of Internal Medicine, Cardinal Tien Hospital, Hsiendian, New Taipei City 23148, Taiwan

⁹ Slone Epidemiology Center, Boston University, Boston, MA 02215, USA

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5789-5802; https://doi.org/10.3390/ijms16035789 - 12 Mar 2015

Cited by 61 | Viewed by 9286

Abstract

Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate [...] Read more.

Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H₂O₂ induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH₂ terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD. Full article

(This article belongs to the Collection Radiation Toxicity in Cells)

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27 pages, 986 KiB

Open AccessReview

Methodologies and Perspectives of Proteomics Applied to Filamentous Fungi: From Sample Preparation to Secretome Analysis

by Linda Bianco and Gaetano Perrotta^*

UTTRI-GENER Genetics and Genomics for Energy and Environment Laboratory—ENEA TRISAIA Research Center, 75025 Rotondella (Matera), Italy

Int. J. Mol. Sci. 2015, 16(3), 5803-5829; https://doi.org/10.3390/ijms16035803 - 12 Mar 2015

Cited by 58 | Viewed by 11267

Abstract

Filamentous fungi possess the extraordinary ability to digest complex biomasses and mineralize numerous xenobiotics, as consequence of their aptitude to sensing the environment and regulating their intra and extra cellular proteins, producing drastic changes in proteome and secretome composition. Recent advancement in proteomic [...] Read more.

Filamentous fungi possess the extraordinary ability to digest complex biomasses and mineralize numerous xenobiotics, as consequence of their aptitude to sensing the environment and regulating their intra and extra cellular proteins, producing drastic changes in proteome and secretome composition. Recent advancement in proteomic technologies offers an exciting opportunity to reveal the fluctuations of fungal proteins and enzymes, responsible for their metabolic adaptation to a large variety of environmental conditions. Here, an overview of the most commonly used proteomic strategies will be provided; this paper will range from sample preparation to gel-free and gel-based proteomics, discussing pros and cons of each mentioned state-of-the-art technique. The main focus will be kept on filamentous fungi. Due to the biotechnological relevance of lignocellulose degrading fungi, special attention will be finally given to their extracellular proteome, or secretome. Secreted proteins and enzymes will be discussed in relation to their involvement in bio-based processes, such as biomass deconstruction and mycoremediation. Full article

(This article belongs to the Special Issue Advances in Proteomic Research)

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9 pages, 718 KiB

Open AccessArticle

A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility

by Cinzia Ciccacci¹, Sara Rufini¹, Sandro Mancinelli², Ersilia Buonomo², Emiliano Giardina^1,3, Paola Scarcella², Maria C. Marazzi⁴, Giuseppe Novelli¹

, Leonardo Palombi² and Paola Borgiani^1,*

¹ Department of Biomedicine and Prevention, Genetics Section, University of Rome “Tor Vergata”, Rome 00133, Italy

² Department of Biomedicine and Prevention, Epidemiology Section, University of Rome “Tor Vergata”, Rome 00133, Italy

³ Laboratory of Molecular Genetics UILDM, Fondazione Santa Lucia, Rome 00179, Italy

⁴ Department of Human Sciences, LUMSA University, Rome 00193, Italy

Int. J. Mol. Sci. 2015, 16(3), 5830-5838; https://doi.org/10.3390/ijms16035830 - 12 Mar 2015

Cited by 10 | Viewed by 5746

Abstract

Steven–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe adverse drug reactions, characterized by extensive epidermal detachment and erosions of mucous membrane. SJS/TEN is one of the most serious adverse reactions to Nevirapine (NVP) treatment, commonly used in developing countries as first-line [...] Read more.

Steven–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe adverse drug reactions, characterized by extensive epidermal detachment and erosions of mucous membrane. SJS/TEN is one of the most serious adverse reactions to Nevirapine (NVP) treatment, commonly used in developing countries as first-line treatment of human immunodeficiency virus infection. In the last years TRAF3IP2 gene variants had been described as associated with susceptibility to several diseases such as psoriasis and psoriatic arthritis. We hypothesized that this gene, involved in immune response and in NF-κB activation, could also be implicated in the SJS/TEN susceptibility. We performed a full resequencing of TRAF3IP2 gene in a population of patients treated with NVP. Twenty-seven patients with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were enrolled. We identified eight exonic and three intronic already described variants. The case/control association analysis highlighted an association between the rs76228616 SNP in exon 2 and the SJS/TEN susceptibility. In particular, the variant allele (C) resulted significantly associated with a higher risk to develop SJS/TEN (p = 0.012 and OR = 3.65 (95% CI 1.33–10.01)). A multivariate analysis by logistic regression confirmed its significant contribution (p = 0.027, OR = 4.39 (95% CI 1.19–16.23)). In conclusion, our study suggests that a variant in TRAF3IP2 gene could be involved in susceptibility to SJS/TEN. Full article

(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)

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25 pages, 2297 KiB

Open AccessArticle

The CENP-T C-Terminus Is Exclusively Proximal to H3.1 and not to H3.2 or H3.3

by Christian Abendroth¹, Antje Hofmeister¹, Sandra B. Hake², Paul K. Kamweru¹, Elke Miess¹, Carsten Dornblut¹, Isabell Küffner¹, Wen Deng³, Heinrich Leonhardt³, Sandra Orthaus⁴, Christian Hoischen¹ and Stephan Diekmann^1,*

¹ Molecular Biology, Fritz Lipmann Institute, Beutenbergstr. 11, D-07745 Jena, Germany

² Department of Molecular Biology, Center for Integrated Protein Science Munich (CIPSM), Adolf-Butenandt-Institute, Ludwig-Maximilians-Universität Munich, Schillerstr. 44, D-80336 Munich, Germany

³ Department of Biology II, Center for Integrated Protein Science, Ludwig-Maximilians-Universität Munich, Planegg-Martinsried, D-82152 Munich, Germany

⁴ PicoQuant GmbH, Kekulestr. 7, D-12489 Berlin, Germany

Int. J. Mol. Sci. 2015, 16(3), 5839-5863; https://doi.org/10.3390/ijms16035839 - 12 Mar 2015

Cited by 6 | Viewed by 8773

Abstract

The kinetochore proteins assemble onto centromeric chromatin and regulate DNA segregation during cell division. The inner kinetochore proteins bind centromeres while most outer kinetochore proteins assemble at centromeres during mitosis, connecting the complex to microtubules. The centromere–kinetochore complex contains specific nucleosomes and nucleosomal [...] Read more.

The kinetochore proteins assemble onto centromeric chromatin and regulate DNA segregation during cell division. The inner kinetochore proteins bind centromeres while most outer kinetochore proteins assemble at centromeres during mitosis, connecting the complex to microtubules. The centromere–kinetochore complex contains specific nucleosomes and nucleosomal particles. CENP-A replaces canonical H3 in centromeric nucleosomes, defining centromeric chromatin. Next to CENP-A, the CCAN multi-protein complex settles which contains CENP-T/W/S/X. These four proteins are described to form a nucleosomal particle at centromeres. We had found the CENP-T C-terminus and the CENP-S termini next to histone H3.1 but not to CENP-A, suggesting that the Constitutive Centromere-Associated Network (CCAN) bridges a CENP-A- and a H3-containing nucleosome. Here, we show by in vivo FRET that this proximity between CENP-T and H3 is specific for H3.1 but neither for the H3.1 mutants H3.1^C96A and H3.1^C110A nor for H3.2 or H3.3. We also found CENP-M next to H3.1 but not to these H3.1 mutants. Consistently, we detected CENP-M next to CENP-S. These data elucidate the local molecular neighborhood of CCAN proteins next to a H3.1-containing centromeric nucleosome. They also indicate an exclusive position of H3.1 clearly distinct from H3.2, thus documenting a local, and potentially also functional, difference between H3.1 and H3.2. Full article

(This article belongs to the Special Issue Förster Resonance Energy Transfer (FRET) 2015)

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22 pages, 3302 KiB

Open AccessArticle

Microarray Analysis on Gene Regulation by Estrogen, Progesterone and Tamoxifen in Human Endometrial Stromal Cells

by Chun-E Ren^1,†, Xueqiong Zhu^2,†, Jinping Li^3,4,5,†, Christian Lyle⁶, Sean Dowdy⁷, Karl C. Podratz⁷, David Byck⁴, Hai-Bin Chen^8,* and Shi-Wen Jiang^3,4,9,*

¹ Department of Obstetrics and Gynecology, Center of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang 261043, China

² Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325001, China

³ Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA 31404, USA

⁴ Department of Obstetrics and Gynecology, Memorial Health University Medical Center, Savannah, GA 31404, USA

⁵ Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA

⁶ Department of Biology, Savannah State University, Savannah, GA 31419, USA

⁷ Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN 55905, USA

⁸ Department of Histology and Embryology, Shantou University Medical College, Shantou 515041, China

⁹ Curtis and Elizabeth Anderson Cancer Institute, Department of Laboratory Oncology Research, Memorial University Medical Center, Savannah, GA 31404, USA

^† These authors contributed equally to the work.

Int. J. Mol. Sci. 2015, 16(3), 5864-5885; https://doi.org/10.3390/ijms16035864 - 13 Mar 2015

Cited by 19 | Viewed by 8694

Abstract

Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from [...] Read more.

Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies. Full article

(This article belongs to the Special Issue Advances in Reproductive Biology)

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14 pages, 933 KiB

Open AccessArticle

Accurate Splicing of HDAC6 Pre-mRNA Requires SON

by Vishnu Priya Battini, Athanasios Bubulya and Paula A. Bubulya^*

Department of Biological Sciences, Wright State University, Dayton, OH 45435, USA

Int. J. Mol. Sci. 2015, 16(3), 5886-5899; https://doi.org/10.3390/ijms16035886 - 13 Mar 2015

Cited by 1 | Viewed by 5442

Abstract

Pre-mRNA splicing requires proper splice site selection mediated by many factors including snRNPs and serine-arginine rich (SR) splicing factors. Our lab previously reported that the SR-like protein SON maintains organization of pre-mRNA splicing factors in nuclear speckles as well as splicing of many [...] Read more.

Pre-mRNA splicing requires proper splice site selection mediated by many factors including snRNPs and serine-arginine rich (SR) splicing factors. Our lab previously reported that the SR-like protein SON maintains organization of pre-mRNA splicing factors in nuclear speckles as well as splicing of many human transcripts including mRNAs coding for the chromatin-modifying enzymes HDAC6, ADA and SETD8. However, the mechanism by which SON maintains accurate splicing is unknown. To build tools for understanding SON-dependent pre-mRNA splicing, we constructed a minigene reporter plasmid driving expression of the genomic sequence spanning exons 26 through 29 of HDAC6. Following SON depletion, we observed altered splicing of HDAC6 reporter transcripts that showed exclusion of exons 27 and 28, reflecting the splicing patterns of endogenous HDAC6 mRNA. Importantly, loss of HDAC6 biological function was also observed, as indicated by truncated HDAC6 protein and corresponding absence of aggresome assembly activities of HDAC6 binding-of-ubiquitin zinc finger (BUZ) domain. We therefore propose that SON-mediated splicing regulation of HDAC6 is essential for supporting protein degradation pathways that prevent human disease. Full article

(This article belongs to the Special Issue Pre-mRNA Splicing)

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22 pages, 1534 KiB

Open AccessArticle

Positive Selection and Functional Divergence of R2R3-MYB Paralogous Genes Expressed in Inflorescence Buds of Scutellaria Species (Labiatae)

by Bing-Hong Huang¹, Erli Pang², Yi-Wen Chen³, Huifen Cao², Yu Ruan^4,5 and Pei-Chun Liao^1,*

¹ Department of Life Science, National Taiwan Normal University, 88, Ting-Chow Rd., Sec. 4, Taipei 116, Taiwan

² Laboratory of Computational Molecular Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China

³ Department of Biological Science and Technology, National Pingtung University of Science and Technology, 1, Shuefu Rd., Neipu, Pingtung 912, Taiwan

⁴ School of Life Science and Engineering, Chongqing Three Gorges University, Chongqing 404001, China

⁵ The College of Forestry, Beijing Forestry University, Beijing 100083, China

Int. J. Mol. Sci. 2015, 16(3), 5900-5921; https://doi.org/10.3390/ijms16035900 - 13 Mar 2015

Cited by 6 | Viewed by 7122

Abstract

Anthocyanin is the main pigment forming floral diversity. Several transcription factors that regulate the expression of anthocyanin biosynthetic genes belong to the R2R3-MYB family. Here we examined the transcriptomes of inflorescence buds of Scutellaria species (skullcaps), identified the expression R2R3-MYBs, [...] Read more.

Anthocyanin is the main pigment forming floral diversity. Several transcription factors that regulate the expression of anthocyanin biosynthetic genes belong to the R2R3-MYB family. Here we examined the transcriptomes of inflorescence buds of Scutellaria species (skullcaps), identified the expression R2R3-MYBs, and detected the genetic signatures of positive selection for adaptive divergence across the rapidly evolving skullcaps. In the inflorescence buds, seven R2R3-MYBs were identified. MYB11 and MYB16 were detected to be positively selected. The signature of positive selection on MYB genes indicated that species diversification could be affected by transcriptional regulation, rather than at the translational level. When comparing among the background lineages of Arabidopsis, tomato, rice, and Amborella, heterogeneous evolutionary rates were detected among MYB paralogs, especially between MYB13 and MYB19. Significantly different evolutionary rates were also evidenced by type-I functional divergence between MYB13 and MYB19, and the accelerated evolutionary rates in MYB19, implied the acquisition of novel functions. Another paralogous pair, MYB2/7 and MYB11, revealed significant radical amino acid changes, indicating divergence in the regulation of different anthocyanin-biosynthetic enzymes. Our findings not only showed that Scutellaria R2R3-MYBs are functionally divergent and positively selected, but also indicated the adaptive relevance of regulatory genes in floral diversification. Full article

(This article belongs to the Special Issue Plant Molecular Biology)

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23 pages, 3294 KiB

Open AccessArticle

Ameliorative Effects of PACAP against Cartilage Degeneration. Morphological, Immunohistochemical and Biochemical Evidence from in Vivo and in Vitro Models of Rat Osteoarthritis

by Salvatore Giunta¹, Alessandro Castorina¹, Rubina Marzagalli¹, Marta Anna Szychlinska¹, Karin Pichler², Ali Mobasheri^3,4,5

and Giuseppe Musumeci^1,*

¹ Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy

² Department of Pediatrics, Clinic for Pediatrics I Medical University of Innsbruck, Anichstr. 35, A-6020 Innsbruck, Austria

³ The D-BOARD European Consortium for Biomarker Discovery, Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK

⁴ Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK

⁵ Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), King AbdulAziz University, Jeddah 21589, Saudi Arabia

Int. J. Mol. Sci. 2015, 16(3), 5922-5944; https://doi.org/10.3390/ijms16035922 - 13 Mar 2015

Cited by 76 | Viewed by 11501 | Correction

Abstract

Osteoarthritis (OA); the most common form of degenerative joint disease, is associated with variations in pro-inflammatory growth factor levels, inflammation and hypocellularity resulting from chondrocyte apoptosis. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide endowed with a range of trophic effects in several [...] Read more.

Osteoarthritis (OA); the most common form of degenerative joint disease, is associated with variations in pro-inflammatory growth factor levels, inflammation and hypocellularity resulting from chondrocyte apoptosis. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide endowed with a range of trophic effects in several cell types; including chondrocytes. However; its role in OA has not been studied. To address this issue, we investigated whether PACAP expression is affected in OA cartilage obtained from experimentally-induced OA rat models, and then studied the effects of PACAP in isolated chondrocytes exposed to IL-1β in vitro to mimic the inflammatory milieu of OA cartilage. OA induction was established by histomorphometric and histochemical analyses. Changes in PACAP distribution in cartilage, or its concentration in synovial fluid (SF), were assessed by immunohistochemistry and ELISA. Results showed that PACAP abundance in cartilage tissue and SF was high in healthy controls. OA induction decreased PACAP levels both in affected cartilage and SF. In vitro, PACAP prevented IL-1β-induced chondrocyte apoptosis, as determined by MTT assay; Hoechst staining and western blots of apoptotic-related proteins. These changes were also accompanied by decreased i-NOS and COX-2 levels, suggesting an anti-inflammatory effect. Altogether, these findings support a potential role for PACAP as a chondroprotective agent for the treatment of OA. Full article

(This article belongs to the Special Issue Apoptotic Chondrocytes and Osteoarthritis)

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30 pages, 736 KiB

Open AccessReview

Molecular Mechanisms of Taste Recognition: Considerations about the Role of Saliva

by Tibor Károly Fábián^1,*, Anita Beck², Pál Fejérdy³, Péter Hermann³ and Gábor Fábián²

¹ Private Practitioner, Ludvigsmindevej 14, st. Faaborg DK-5600, Denmark

² Clinic of Pediatric Dentistry and Orthodontics, Faculty of Dentistry, Semmelweis University Budapest, Szentkirályi utca 47, Budapest H-1088, Hungary

³ Clinic of Prosthetic Dentistry, Faculty of Dentistry, Semmelweis University Budapest, Szentkirályi utca 47, Budapest H-1088, Hungary

Int. J. Mol. Sci. 2015, 16(3), 5945-5974; https://doi.org/10.3390/ijms16035945 - 13 Mar 2015

Cited by 70 | Viewed by 12829

Abstract

The gustatory system plays a critical role in determining food preferences and food intake, in addition to nutritive, energy and electrolyte balance. Fine tuning of the gustatory system is also crucial in this respect. The exact mechanisms that fine tune taste sensitivity are [...] Read more.

The gustatory system plays a critical role in determining food preferences and food intake, in addition to nutritive, energy and electrolyte balance. Fine tuning of the gustatory system is also crucial in this respect. The exact mechanisms that fine tune taste sensitivity are as of yet poorly defined, but it is clear that various effects of saliva on taste recognition are also involved. Specifically those metabolic polypeptides present in the saliva that were classically considered to be gut and appetite hormones (i.e., leptin, ghrelin, insulin, neuropeptide Y, peptide YY) were considered to play a pivotal role. Besides these, data clearly indicate the major role of several other salivary proteins, such as salivary carbonic anhydrase (gustin), proline-rich proteins, cystatins, alpha-amylases, histatins, salivary albumin and mucins. Other proteins like glucagon-like peptide-1, salivary immunoglobulin-A, zinc-α-2-glycoprotein, salivary lactoperoxidase, salivary prolactin-inducible protein and salivary molecular chaperone HSP70/HSPAs were also expected to play an important role. Furthermore, factors including salivary flow rate, buffer capacity and ionic composition of saliva should also be considered. In this paper, the current state of research related to the above and the overall emerging field of taste-related salivary research alongside basic principles of taste perception is reviewed. Full article

(This article belongs to the Section Molecular Recognition)

15 pages, 2030 KiB

Open AccessArticle

RNA-Seq Transcriptome Analysis of Maize Inbred Carrying Nicosulfuron-Tolerant and Nicosulfuron-Susceptible Alleles

by Xiaomin Liu^*

, Xian Xu, Binghua Li, Xueqing Wang, Guiqi Wang^* and Moran Li

Institute of Cereal and Oil Crops, Hebei Academy of Agriculture and Forestry Sciences, Shijiazhuang 050035, Hebei, China

Int. J. Mol. Sci. 2015, 16(3), 5975-5989; https://doi.org/10.3390/ijms16035975 - 13 Mar 2015

Cited by 31 | Viewed by 9046

Abstract

Postemergence applications of nicosulfuron can cause great damage to certain maize inbred lines and hybrids. Variation among different responses to nicosulfuron may be attributed to differential rates of herbicide metabolism. We employed RNA-Seq analysis to compare transcriptome responses between nicosulfuron-treated and untreated in [...] Read more.

Postemergence applications of nicosulfuron can cause great damage to certain maize inbred lines and hybrids. Variation among different responses to nicosulfuron may be attributed to differential rates of herbicide metabolism. We employed RNA-Seq analysis to compare transcriptome responses between nicosulfuron-treated and untreated in both tolerant and susceptible maize plants. A total of 71.8 million paired end Illumina RNA-Seq reads were generated, representing the transcription of around 40,441 unique reads. About 345,171 gene ontology (GO) term assignments were conducted for the annotation in terms of biological process, cellular component and molecular function categories, and 6413 sequences with 108 enzyme commission numbers were assigned to 134 predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways. Digital gene expression profile (DGE) analysis using Solexa sequencing was performed within the susceptible and tolerant maize between the nicosulfuron-treated and untreated conditions, 13 genes were selected as the candidates most likely involved in herbicide metabolism, and quantitative RT-PCR validated the RNA-Seq results for eight genes. This transcriptome data may provide opportunities for the study of sulfonylurea herbicides susceptibility emergence of Zea mays. Full article

(This article belongs to the Special Issue Plant Molecular Biology)

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10 pages, 1480 KiB

Open AccessLetter

Isolation of a Pluripotent Neural Stem Cell from the Embryonic Bovine Brain

by Yuhua Gao^1,2,†, Xiangchen Li^1,2,†, Dong Zheng², Weijun Guan^1,* and Yuehui Ma^1,*

¹ Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China

² College of Wildlife Resources, Northeast Forestry University, Harbin 150040, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 5990-5999; https://doi.org/10.3390/ijms16035990 - 13 Mar 2015

Cited by 6 | Viewed by 6806

Abstract

We recently isolated stem cells derived from the brain of a bovine fetus, utilizing a particular mechanical separation method. After improving our experimental conditions, we obtained neural stem cells using an optimized culture medium system. The cells were expanded, established in continuous cell [...] Read more.

We recently isolated stem cells derived from the brain of a bovine fetus, utilizing a particular mechanical separation method. After improving our experimental conditions, we obtained neural stem cells using an optimized culture medium system. The cells were expanded, established in continuous cell culture and used for immunofluorescence cytochemistry. RT-PCR showed that embryonic neural stem cells (NSCs) not only expresses the protein Sox2, Nestin but also Pax6, Musashi proteins and were differentiated into the three classical neuronal phenotypes (neurons, astrocytes, and oligodendrocytes). Full article

(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)

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18 pages, 16921 KiB

Open AccessArticle

Locus Number Estimation of MHC Class II B in Stone Flounder and Japanese Flounder

by Jiajun Jiang^†, Chunmei Li^†, Quanqi Zhang and Xubo Wang^*

¹ Key Laboratory of Marine Genetics and Breeding (Ocean University of China), Ministry of Education, Qingdao 266003, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 6000-6017; https://doi.org/10.3390/ijms16036000 - 13 Mar 2015

Cited by 4 | Viewed by 5609

Abstract

Members of major histocompatibility complex (MHC) family are important in immune systems. Great efforts have been made to reveal their complicated gene structures. But many existing studies focus on partial sequences of MHC genes. In this study, by gene cloning and sequencing, we [...] Read more.

Members of major histocompatibility complex (MHC) family are important in immune systems. Great efforts have been made to reveal their complicated gene structures. But many existing studies focus on partial sequences of MHC genes. In this study, by gene cloning and sequencing, we identified cDNA sequences and DNA sequences of the MHC class II B in two flatfishes, stone flounder (Kareius bicoloratus) and homozygous diploid Japanese flounder (Paralichthys olivaceus). Eleven cDNA sequences were acquired from eight stone flounder individuals, and most of the polymorphic sites distributed in exons 2 and 3. Twenty-eight alleles were identified from the DNA fragments in these eight individuals. It could be deduced from their Bayesian inference phylogenetic tree that at least four loci of MHC class II B exist in stone flounder. The detailed whole-length DNA sequences in one individual were analyzed, revealing that the intron length varied among different loci. Four different cDNA sequences were identified from one homozygous diploid Japanese flounder individual, implying the existence of at least four loci. Comparison of the cDNA sequences to the DNA sequence confirmed that six exons existed in this gene of Japanese flounder, which was a common feature shared by Pleuronectiformes fishes. Our results proved the multi-locus feature of MHC class II B. The sequences we obtained would provide detailed and systematic data for further research. Full article

(This article belongs to the Section Biochemistry)

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39 pages, 2430 KiB

Open AccessReview

The Effects of Marine Carbohydrates and Glycosylated Compounds on Human Health

by Hee-Kyoung Kang¹, Chang Ho Seo² and Yoonkyung Park^1,3,*

¹ Department of Biomedical Science, Chosun University, Gwangju 501-759, Korea

² Department of Bioinformatics, Kongju National University, Kongju 314-701, Korea

³ Research Center for Proteineous Materials, Chosun University, Gwangju 501-759, Korea

Int. J. Mol. Sci. 2015, 16(3), 6018-6056; https://doi.org/10.3390/ijms16036018 - 16 Mar 2015

Cited by 55 | Viewed by 9239

Abstract

Marine organisms have been recognized as a valuable source of bioactive compounds with industrial and nutraceutical potential. Recently, marine-derived carbohydrates, including polysaccharides and low molecular weight glycosylated oligosaccharides, have attracted much attention because of their numerous health benefits. Moreover, several studies have reported [...] Read more.

Marine organisms have been recognized as a valuable source of bioactive compounds with industrial and nutraceutical potential. Recently, marine-derived carbohydrates, including polysaccharides and low molecular weight glycosylated oligosaccharides, have attracted much attention because of their numerous health benefits. Moreover, several studies have reported that marine carbohydrates exhibit various biological activities, including antioxidant, anti-infection, anticoagulant, anti-inflammatory, and anti-diabetic effects. The present review discusses the potential industrial applications of bioactive marine carbohydrates for health maintenance and disease prevention. Furthermore, the use of marine carbohydrates in food, cosmetics, agriculture, and environmental protection is discussed. Full article

(This article belongs to the Special Issue Bioactive Carbohydrates and Peptides)

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19 pages, 740 KiB

Open AccessArticle

Protease and Hemicellulase Assisted Extraction of Dietary Fiber from Wastes of Cynara cardunculus

by Cinthia Santo Domingo^1,2, Marcelo Soria³, Ana M. Rojas^1,4, Eliana N. Fissore^1,4 and Lía N. Gerschenson^1,4,*

¹ Industry Department, School of Natural and Exact Sciences, Buenos Aires University (UBA), Ciudad Universitaria, 1428 Ciudad Autónoma de Buenos Aires, Argentina

² Fellow of the National Research Council of Argentina (CONICET), 1033 Ciudad Autónoma de Buenos Aires, Argentina

³ Instituto de Investigaciones en Biociencias Agrícolas y Ambientales—INBA (CONICET), School of Agronomy (UBA), 1417 Ciudad Autónoma de Buenos Aires, Argentina

⁴ Member of CONICET, 1033 Ciudad Autónoma de Buenos Aires, Argentina

Int. J. Mol. Sci. 2015, 16(3), 6057-6075; https://doi.org/10.3390/ijms16036057 - 16 Mar 2015

Cited by 25 | Viewed by 6350

Abstract

The action of protease and hemicellulase for the extraction of fractions enriched in soluble fiber from bracts and stems of Cynara cardunculus was evaluated. Using a two-factor simplex design comprising protease amounts of 0–200 μL and hemicellulase amounts of 0–200 mg for 5 [...] Read more.

The action of protease and hemicellulase for the extraction of fractions enriched in soluble fiber from bracts and stems of Cynara cardunculus was evaluated. Using a two-factor simplex design comprising protease amounts of 0–200 μL and hemicellulase amounts of 0–200 mg for 5 g of material, we explored the effect of a 5 h enzymatic treatment at 40 °C on the chemical composition and yield of the fractions isolated. The fractions contained inulin and pectin. In general, the protein, inulin, and polyphenol contents and also the yields were higher for fractions obtained from stems. The most marked effects were observed when enzymes were used at higher concentrations, especially for hemicellulase. The inclusion of a pre-heating step increased the yield and the inulin content for fractions isolated from bracts and stems and decreased the protein and polyphenol contents, and the galacturonic acid for bracts. These fractions, in general, contained the polyphenolic compounds monocaffeoylquinic acid, apigenin, and pinoresinol. Full article

(This article belongs to the Special Issue Green Chemistry and the Biorefinery)

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17 pages, 1390 KiB

Open AccessReview

Conformational Analysis of Misfolded Protein Aggregation by FRET and Live-Cell Imaging Techniques

by Akira Kitamura^1,*

, Kazuhiro Nagata² and Masataka Kinjo¹

¹ Laboratory of Molecular Cell Dynamics, Faculty of Advanced Life Science, Hokkaido University, Sapporo 001-0021, Japan

² Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan

Int. J. Mol. Sci. 2015, 16(3), 6076-6092; https://doi.org/10.3390/ijms16036076 - 16 Mar 2015

Cited by 25 | Viewed by 11555

Abstract

Cellular homeostasis is maintained by several types of protein machinery, including molecular chaperones and proteolysis systems. Dysregulation of the proteome disrupts homeostasis in cells, tissues, and the organism as a whole, and has been hypothesized to cause neurodegenerative disorders, including amyotrophic lateral sclerosis [...] Read more.

Cellular homeostasis is maintained by several types of protein machinery, including molecular chaperones and proteolysis systems. Dysregulation of the proteome disrupts homeostasis in cells, tissues, and the organism as a whole, and has been hypothesized to cause neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). A hallmark of neurodegenerative disorders is formation of ubiquitin-positive inclusion bodies in neurons, suggesting that the aggregation process of misfolded proteins changes during disease progression. Hence, high-throughput determination of soluble oligomers during the aggregation process, as well as the conformation of sequestered proteins in inclusion bodies, is essential for elucidation of physiological regulation mechanism and drug discovery in this field. To elucidate the interaction, accumulation, and conformation of aggregation-prone proteins, in situ spectroscopic imaging techniques, such as Förster/fluorescence resonance energy transfer (FRET), fluorescence correlation spectroscopy (FCS), and bimolecular fluorescence complementation (BiFC) have been employed. Here, we summarize recent reports in which these techniques were applied to the analysis of aggregation-prone proteins (in particular their dimerization, interactions, and conformational changes), and describe several fluorescent indicators used for real-time observation of physiological states related to proteostasis. Full article

(This article belongs to the Special Issue Förster Resonance Energy Transfer (FRET) 2015)

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20 pages, 1462 KiB

Open AccessReview

Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression

by Giuseppe Musumeci^1,*

, Flavia Concetta Aiello¹, Marta Anna Szychlinska¹, Michelino Di Rosa², Paola Castrogiovanni¹

and Ali Mobasheri^3,4,5

¹ Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy

² Department of Biomedical and Biotechnological Sciences, Pathology Section, School of Medicine, University of Catania, 95123 Catania, Italy

³ The D-BOARD European Consortium for Biomarker Discovery, Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK

⁴ Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK

⁵ Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), King AbdulAziz University, Jeddah 21589, Saudi Arabia

Int. J. Mol. Sci. 2015, 16(3), 6093-6112; https://doi.org/10.3390/ijms16036093 - 16 Mar 2015

Cited by 294 | Viewed by 24329

Abstract

Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks [...] Read more.

Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by “low-grade inflammation” in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder. Full article

(This article belongs to the Special Issue Apoptotic Chondrocytes and Osteoarthritis)

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11 pages, 5110 KiB

Open AccessArticle

In Vitro Corrosion and Cytocompatibility Properties of Nano-Whisker Hydroxyapatite Coating on Magnesium Alloy for Bone Tissue Engineering Applications

by Huawei Yang^1,†, Xueyu Yan^1,†, Min Ling², Zuquan Xiong^3,*, Caiwen Ou⁴ and Wei Lu^2,*

¹ Departmentof Dentistry, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China

² Shanghai Key Laboratory of Development and Application for Metal-Functional Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, China

³ Department of Urology, Huashan Hospital, Fudan University, Shanghai 200031, China

⁴ Department of Science and Technology, Southern Medical University, Guangzhou 510515, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 6113-6123; https://doi.org/10.3390/ijms16036113 - 17 Mar 2015

Cited by 25 | Viewed by 7050

Abstract

We report here the successful fabrication of nano-whisker hydroxyapatite (nHA) coatings on Mg alloy by using a simple one-step hydrothermal process in aqueous solution. The nHA coating shows uniform structure and high crystallinity. Results indicate that nHA coating is promising for improving the [...] Read more.

We report here the successful fabrication of nano-whisker hydroxyapatite (nHA) coatings on Mg alloy by using a simple one-step hydrothermal process in aqueous solution. The nHA coating shows uniform structure and high crystallinity. Results indicate that nHA coating is promising for improving the in vitro corrosion and cytocompatibility properties of Mg-based implants and devices for bone tissue engineering. In addition, the simple hydrothermal deposition method used in the current study is also applicable to substrates with complex shapes or surface geometries. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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16 pages, 1068 KiB

Open AccessReview

Chemopreventive Potential of Green Tea Catechins in Hepatocellular Carcinoma

by Masahito Shimizu^*, Yohei Shirakami, Hiroyasu Sakai

, Masaya Kubota, Takahiro Kochi, Takayasu Ideta, Tsuneyuki Miyazaki and Hisataka Moriwaki

Department of Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan

Int. J. Mol. Sci. 2015, 16(3), 6124-6139; https://doi.org/10.3390/ijms16036124 - 17 Mar 2015

Cited by 44 | Viewed by 9251

Abstract

Hepatocellular carcinoma (HCC), which is a common malignancy worldwide, usually develops in a cirrhotic liver due to hepatitis virus infection. Metabolic syndrome, which is frequently complicated by obesity and diabetes mellitus, is also a critical risk factor for liver carcinogenesis. Green tea catechins [...] Read more.

Hepatocellular carcinoma (HCC), which is a common malignancy worldwide, usually develops in a cirrhotic liver due to hepatitis virus infection. Metabolic syndrome, which is frequently complicated by obesity and diabetes mellitus, is also a critical risk factor for liver carcinogenesis. Green tea catechins (GTCs) may possess potent anticancer and chemopreventive properties for a number of different malignancies, including liver cancer. Antioxidant and anti-inflammatory activities are key mechanisms through which GTCs prevent the development of neoplasms, and they also exert cancer chemopreventive effects by modulating several signaling transduction and metabolic pathways. Furthermore, GTCs are considered to be useful for the prevention of obesity- and metabolic syndrome-related carcinogenesis by improving metabolic disorders. Several interventional trials in humans have shown that GTCs may ameliorate metabolic abnormalities and prevent the development of precancerous lesions. The purpose of this article is to review the key mechanisms by which GTCs exert chemopreventive effects in liver carcinogenesis, focusing especially on their ability to inhibit receptor tyrosine kinases and improve metabolic abnormalities. We also review the evidence for GTCs acting to prevent metabolic syndrome-associated liver carcinogenesis. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Functional Foods for Cancer Prevention)

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13 pages, 1776 KiB

Open AccessArticle

Polyoxygenated Cembrane Diterpenoids from the Soft Coral Sarcophyton ehrenbergi

by Shi-Yie Cheng¹, Shang-Kwei Wang², Mu-Keng Hsieh³ and Chang-Yih Duh^3,4,*

¹ Department of Life Sciences, National University of Kaohsiung, Kaohsiung 811, Taiwan

² Department of Microbiology, Kaohsiung Medical University, Kaohsiung 807, Taiwan

³ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan

⁴ Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Int. J. Mol. Sci. 2015, 16(3), 6140-6152; https://doi.org/10.3390/ijms16036140 - 17 Mar 2015

Cited by 14 | Viewed by 5563

Abstract

Five new polyoxygenated cembranoids, named (+)-1,15-epoxy-2-methoxy-12-methoxycarbonyl-11E-sarcophytoxide (1), (+)-2-epi-12-methoxycarbonyl-11E-sarcophine (2), 3,4-epoxyehrenberoxide A (3), ehrenbergol D (4) and ehrenbergol E (5), were obtained from the soft coral Sarcophyton ehrenbergi [...] Read more.

Five new polyoxygenated cembranoids, named (+)-1,15-epoxy-2-methoxy-12-methoxycarbonyl-11E-sarcophytoxide (1), (+)-2-epi-12-methoxycarbonyl-11E-sarcophine (2), 3,4-epoxyehrenberoxide A (3), ehrenbergol D (4) and ehrenbergol E (5), were obtained from the soft coral Sarcophyton ehrenbergi. The structures of 1–5 were established on the basis of comprehensive NMR and HR-ESI-MS analyses and by comparison with reported data in the literature. Compounds 4 and 5 showed moderate cytotoxicity against P-388 (mouse lymphocytic leukemia) cancer cell line with EC₅₀ values of 2.0 and 3.0 μM, respectively. Compound 2 exhibited slight antiviral activity against HCMV (human cytomegalovirus) with IC₅₀ values of 25.0 μg/mL. Full article

(This article belongs to the Section Biochemistry)

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30 pages, 892 KiB

Open AccessReview

New Therapies for Dedifferentiated Papillary Thyroid Cancer

by Poupak Fallahi¹, Valeria Mazzi¹, Roberto Vita², Silvia Martina Ferrari¹, Gabriele Materazzi³, David Galleri³, Salvatore Benvenga², Paolo Miccoli³ and Alessandro Antonelli^1,*

¹ Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126 Pisa, Italy

² Department of Clinical & Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti, 1, 98122 Messina, Italy

³ Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Via Savi, 10, 56126 Pisa, Italy

Int. J. Mol. Sci. 2015, 16(3), 6153-6182; https://doi.org/10.3390/ijms16036153 - 17 Mar 2015

Cited by 50 | Viewed by 10281

Abstract

The number of thyroid cancers is increasing. Standard treatment usually includes primary surgery, thyroid-stimulating hormone suppressive therapy, and ablation of the thyroid remnant with radioactive iodine (RAI). Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, [...] Read more.

The number of thyroid cancers is increasing. Standard treatment usually includes primary surgery, thyroid-stimulating hormone suppressive therapy, and ablation of the thyroid remnant with radioactive iodine (RAI). Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, which fails to respond to RAI, exhibiting a more aggressive behavior. The lack of specific, effective and well-tolerated drugs, the scarcity of data about the association of multi-targeting drugs, and the limited role of radioiodine for dedifferentiated thyroid cancer, call for further efforts in the field of new drugs development. Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF proto-oncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways playing a crucial role in the development of thyroid cancer. Targeted novel compounds have been demonstrated to induce clinical responses and stabilization of disease. Sorafenib has been approved for differentiated thyroid cancer refractory to RAI. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology 2014)

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19 pages, 806 KiB

Open AccessReview

DNA Damage: A Sensible Mediator of the Differentiation Decision in Hematopoietic Stem Cells and in Leukemia

by Cary N. Weiss and Keisuke Ito^*

Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Departments of Cell Biology/Stem Cell Institute and Medicine, Albert Einstein Cancer Center and Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA

Int. J. Mol. Sci. 2015, 16(3), 6183-6201; https://doi.org/10.3390/ijms16036183 - 17 Mar 2015

Cited by 29 | Viewed by 10162

Abstract

In the adult, the source of functionally diverse, mature blood cells are hematopoietic stem cells, a rare population of quiescent cells that reside in the bone marrow niche. Like stem cells in other tissues, hematopoietic stem cells are defined by their ability to [...] Read more.

In the adult, the source of functionally diverse, mature blood cells are hematopoietic stem cells, a rare population of quiescent cells that reside in the bone marrow niche. Like stem cells in other tissues, hematopoietic stem cells are defined by their ability to self-renew, in order to maintain the stem cell population for the lifetime of the organism, and to differentiate, in order to give rise to the multiple lineages of the hematopoietic system. In recent years, increasing evidence has suggested a role for the accumulation of reactive oxygen species and DNA damage in the decision for hematopoietic stem cells to exit quiescence and to differentiate. In this review, we will examine recent work supporting the idea that detection of cell stressors, such as oxidative and genetic damage, is an important mediator of cell fate decisions in hematopoietic stem cells. We will explore the benefits of such a system in avoiding the development and progression of malignancies, and in avoiding tissue exhaustion and failure. Additionally, we will discuss new work that examines the accumulation of DNA damage and replication stress in aging hematopoietic stem cells and causes us to rethink ideas of genoprotection in the bone marrow niche. Full article

(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases 2014)

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15 pages, 13280 KiB

Open AccessArticle

Effect of Chemical Treatments on Flax Fibre Reinforced Polypropylene Composites on Tensile and Dome Forming Behaviour

by Wentian Wang^*, Adrian Lowe^† and Shankar Kalyanasundaram^†

¹ Research School of Engineering, Australian National University, North Road, Canberra 0200, Australia

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 6202-6216; https://doi.org/10.3390/ijms16036202 - 17 Mar 2015

Cited by 10 | Viewed by 4962

Abstract

Tensile tests were performed on two different natural fibre composites (same constituent material, similar fibre fraction and thickness but different weave structure) to determine changes in mechanical properties caused by various aqueous chemical treatments and whether any permanent changes remain on drying. Scanning [...] Read more.

Tensile tests were performed on two different natural fibre composites (same constituent material, similar fibre fraction and thickness but different weave structure) to determine changes in mechanical properties caused by various aqueous chemical treatments and whether any permanent changes remain on drying. Scanning electronic microscopic examinations suggested that flax fibres and the flax/polypropylene interface were affected by the treatments resulting in tensile property variations. The ductility of natural fibre composites was improved significantly under wet condition and mechanical properties (elongation-to-failure, stiffness and strength) can almost retain back to pre-treated levels when dried from wet condition. Preheating is usually required to improve the formability of material in rapid forming, and the chemical treatments performed in this study were far more effective than preheating. The major breakthrough in improving the formability of natural fibre composites can aid in rapid forming of this class of material system. Full article

(This article belongs to the Special Issue Advances in Anisotropic and Smart Materials)

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18 pages, 3421 KiB

Open AccessArticle

Molecular Dynamics Simulations of Acylpeptide Hydrolase Bound to Chlorpyrifosmethyl Oxon and Dichlorvos

by Hanyong Jin^1,†, Zhenhuan Zhou^2,†, Dongmei Wang¹, Shanshan Guan³ and Weiwei Han^1,*

¹ Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130023, China

² Second Bethune Hospital of Jilin University, Changchun 130041, China

³ State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 6217-6234; https://doi.org/10.3390/ijms16036217 - 18 Mar 2015

Cited by 21 | Viewed by 6885

Abstract

Acylpeptide hydrolases (APHs) catalyze the removal of N-acylated amino acids from blocked peptides. Like other prolyloligopeptidase (POP) family members, APHs are believed to be important targets for drug design. To date, the binding pose of organophosphorus (OP) compounds of APH, as well [...] Read more.

Acylpeptide hydrolases (APHs) catalyze the removal of N-acylated amino acids from blocked peptides. Like other prolyloligopeptidase (POP) family members, APHs are believed to be important targets for drug design. To date, the binding pose of organophosphorus (OP) compounds of APH, as well as the different OP compounds binding and inducing conformational changes in two domains, namely, α/β hydrolase and β-propeller, remain poorly understood. We report a computational study of APH bound to chlorpyrifosmethyl oxon and dichlorvos. In our docking study, Val471 and Gly368 are important residues for chlorpyrifosmethyl oxon and dichlorvos binding. Molecular dynamics simulations were also performed to explore the conformational changes between the chlorpyrifosmethyl oxon and dichlorvos bound to APH, which indicated that the structural feature of chlorpyrifosmethyl oxon binding in APH permitted partial opening of the β-propeller fold and allowed the chlorpyrifosmethyl oxon to easily enter the catalytic site. These results may facilitate the design of APH-targeting drugs with improved efficacy. Full article

(This article belongs to the Special Issue Proteins and Protein-Ligand Interactions)

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16 pages, 854 KiB

Open AccessArticle

Abortive Infection of Snakehead Fish Vesiculovirus in ZF4 Cells Was Associated with the RLRs Pathway Activation by Viral Replicative Intermediates

by Wenwen Wang^1,2, Muhammad Asim¹, Lizhu Yi¹, Abeer M. Hegazy^1,3, Xianqin Hu^1,4, Yang Zhou¹, Taoshan Ai⁵ and Li Lin^1,2,6,*

¹ Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China

² Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, China

³ Central Laboratory for Environmental Quality Monitoring (CLEQM), National Water Research Center (NWRC), El-Kanater 13621, Egypt

⁴ School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China

⁵ Wuhan Fishery Research Institute, Wuhan 430207, China

⁶ Key Lab of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, China

Int. J. Mol. Sci. 2015, 16(3), 6235-6250; https://doi.org/10.3390/ijms16036235 - 18 Mar 2015

Cited by 26 | Viewed by 7970

Abstract

Snakehead fish vesiculovirus (SHVV) is a negative strand RNA virus which can cause great economic losses in fish culture. To facilitate the study of SHVV-host interactions, the susceptibility of zebrafish embryonic fibroblast cell line (ZF4) to the SHVV was investigated in this report. [...] Read more.

Snakehead fish vesiculovirus (SHVV) is a negative strand RNA virus which can cause great economic losses in fish culture. To facilitate the study of SHVV-host interactions, the susceptibility of zebrafish embryonic fibroblast cell line (ZF4) to the SHVV was investigated in this report. The results showed that high amount of viral mRNAs and cRNAs were detected at the 3 h post-infection. However, the expressions of the viral mRNAs and cRNA were decreased dramatically after 6 h post-infection. In addition, the expressions of interferon (IFN) and interferon-induced GTP-binding protein Mx were all up regulated significantly at the late stage of the infection. Meanwhile, the expressions of Retinoic acid-inducible gene I (RIG-I) and Melanoma differentiation-associated gene 5 (MDA5) were also all up-regulated significantly during the infection. Two isoforms of DrLGP2 from zebrafish were also cloned and analyzed. Interestingly, the expression of DrLGP2a but not DrLGP2b was significantly up-regulated at both mRNA and protein levels, indicating that the two DrLGP2 isoforms might play different roles during the SHVV infection. Transfection experiment showed that viral replicative intermediates were required for the activation of IFN-α expression. Taken together, the abortive infection of SHVV in ZF4 cells was associated with the activation of RLRs pathway, which was activated by viral replicative intermediates. Full article

(This article belongs to the Special Issue Fish Molecular Biology)

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15 pages, 872 KiB

Open AccessArticle

Prediction of Long-Term Treatment Response to Selective Serotonin Reuptake Inhibitors (SSRIs) Using Scalp and Source Loudness Dependence of Auditory Evoked Potentials (LDAEP) Analysis in Patients with Major Depressive Disorder

by Bun-Hee Lee¹, Young-Min Park^2,*

, Seung-Hwan Lee^2,3 and Miseon Shim^3,4

¹ Department of Psychiatry, Seoul Eunpyeong Hospital, 90, Baengnyeonsan-ro, Eunpyeong-gu, Seoul 122-913, Korea

² Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, 2240, Daehwa-dong, Ilsanseo-gu, Goyang 411-706, Korea

³ Clinical Emotion and Cognition Research Laboratory, Inje University, Goyang 411-706, Korea

⁴ Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Korea

Int. J. Mol. Sci. 2015, 16(3), 6251-6265; https://doi.org/10.3390/ijms16036251 - 18 Mar 2015

Cited by 33 | Viewed by 7072

Abstract

Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP) is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less [...] Read more.

Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP) is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD). Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day), sertraline (n = 7, 78.6 ± 26.7 mg/day), and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day)) for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI) score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036). In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009). There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041). Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 3036 KiB

Open AccessArticle

DNA Synthesis during Endomitosis Is Stimulated by Insulin via the PI3K/Akt and TOR Signaling Pathways in the Silk Gland Cells of Bombyx mori

by Yaofeng Li^1,†, Xiangyun Chen^1,†, Xiaofang Tang¹, Chundong Zhang^1,3, La Wang¹

, Peng Chen¹, Minhui Pan^1,2,* and Cheng Lu^1,2,*

¹ State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, China

² Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry, Southwest University, Chongqing 400716, China

³ Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China

Int. J. Mol. Sci. 2015, 16(3), 6266-6280; https://doi.org/10.3390/ijms16036266 - 18 Mar 2015

Cited by 20 | Viewed by 7574

Abstract

Silk gland cells undergo multiple endomitotic cell cycles during silkworm larval ontogeny. Our previous study demonstrated that feeding is required for continued endomitosis in the silk gland cells of silkworm larvae. Furthermore, the insulin signaling pathway is closely related to nutritional signals. To [...] Read more.

Silk gland cells undergo multiple endomitotic cell cycles during silkworm larval ontogeny. Our previous study demonstrated that feeding is required for continued endomitosis in the silk gland cells of silkworm larvae. Furthermore, the insulin signaling pathway is closely related to nutritional signals. To investigate whether the insulin signaling pathway is involved in endomitosis in silk gland cells, in this study, we initially analyzed the effects of bovine insulin on DNA synthesis in endomitotic silk gland cells using 5-bromo-2'-deoxyuridine (BrdU) labeling technology, and found that bovine insulin can stimulate DNA synthesis. Insulin signal transduction is mainly mediated via phosphoinositide 3-kinase (PI3K)/Akt, the target of rapamycin (TOR) and the extracellular signal-regulated kinase (ERK) pathways in vertebrates. We ascertained that these three pathways are involved in DNA synthesis in endomitotic silk gland cells using specific inhibitors against each pathway. Moreover, we investigated whether these three pathways are involved in insulin-stimulated DNA synthesis in endomitotic silk gland cells, and found that the PI3K/Akt and TOR pathways, but not the ERK pathway, are involved in this process. These results provide an important theoretical foundation for the further investigations of the mechanism underlying efficient endomitosis in silk gland cells. Full article

(This article belongs to the Section Biochemistry)

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17 pages, 570 KiB

Open AccessReview

Role of Pancreatic Transcription Factors in Maintenance of Mature β-Cell Function

by Hideaki Kaneto^1,* and Taka-aki Matsuoka²

¹ Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577, Matsushima, Kurashiki 701-0192, Japan

² Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

Int. J. Mol. Sci. 2015, 16(3), 6281-6297; https://doi.org/10.3390/ijms16036281 - 18 Mar 2015

Cited by 59 | Viewed by 10971

Abstract

A variety of pancreatic transcription factors including PDX-1 and MafA play crucial roles in the pancreas and function for the maintenance of mature β-cell function. However, when β-cells are chronically exposed to hyperglycemia, expression and/or activities of such transcription factors are reduced, which [...] Read more.

A variety of pancreatic transcription factors including PDX-1 and MafA play crucial roles in the pancreas and function for the maintenance of mature β-cell function. However, when β-cells are chronically exposed to hyperglycemia, expression and/or activities of such transcription factors are reduced, which leads to deterioration of b-cell function. These phenomena are well known as β-cell glucose toxicity in practical medicine as well as in the islet biology research area. Here we describe the possible mechanism for β-cell glucose toxicity found in type 2 diabetes. It is likely that reduced expression levels of PDX-1 and MafA lead to suppression of insulin biosynthesis and secretion. In addition, expression levels of incretin receptors (GLP-1 and GIP receptors) in β-cells are decreased, which likely contributes to the impaired incretin effects found in diabetes. Taken together, down-regulation of insulin gene transcription factors and incretin receptors explains, at least in part, the molecular mechanism for β-cell glucose toxicity. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 762 KiB

Open AccessArticle

Genotyping Test with Clinical Factors: Better Management of Acute Postoperative Pain?

by Aline Hajj^1,2,*, Katell Peoc'h², Jean-Louis Laplanche², Hicham Jabbour³, Nicole Naccache³, Hicham Abou Zeid³, Patricia Yazbeck³ and Lydia Rabbaa Khabbaz¹

¹ Laboratoire de Pharmacologie, Pharmacie Clinique et Contrôle de Qualité des Médicaments, Faculté de Pharmacie, Saint-Joseph University of Beirut, B.P. 11-5076-Riad El Solh, Beirut 1107 2180, Lebanon

² Université Paris Descartes, Unité INSERM UMR-S 1144, Paris F-75006, France

³ Department of Anesthesia and Critical Care, Hôtel-Dieu de France Hospital-Saint-Joseph University of Beirut, B.P. 16-6830, Beirut 1100 2160, Lebanon

Int. J. Mol. Sci. 2015, 16(3), 6298-6311; https://doi.org/10.3390/ijms16036298 - 19 Mar 2015

Cited by 14 | Viewed by 6510

Abstract

Individualization of acute postoperative pain treatment on an evidence-based decision process is a major health concern. The aim of this study is to investigate the influence of genetic and non-genetic factors on the variability of response to morphine in acute postoperative pain. A [...] Read more.

Individualization of acute postoperative pain treatment on an evidence-based decision process is a major health concern. The aim of this study is to investigate the influence of genetic and non-genetic factors on the variability of response to morphine in acute postoperative pain. A group of nighty-five patients undergoing major surgery were included prospectively. At 24 h, a logistic regression model was carried out to determine the factors associated with morphine doses given by a Patient Controlled Analgesia device. The dose of morphine was associated with age (p = 0.011), patient weight (p = 0.025) and the duration of operation (p = 0.030). This dose decreased with patient’s age and duration of operation and increased with patient’s weight. OPRM1 and ABCB1 polymorphisms were significantly associated with administered dose of morphine (p = 0.038 and 0.012 respectively). Patients with at least one G allele for c.118A>G OPRM1 polymorphism (AG/GG) needed 4 times the dose of morphine of AA patients. Additionally, patients with ABCB1 CT and CC genotypes for c.3435C>T polymorphism were 5.6 to 7.1 times more prone to receive higher dose of morphine than TT patients. Our preliminary results support the evidence that OPRM1/ABCB1 genotypes along with age, weight and duration of operation have an impact on morphine consumption for acute postoperative pain treatment. Full article

(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)

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25 pages, 843 KiB

Open AccessReview

Mitochondria as Key Targets of Cardioprotection in Cardiac Ischemic Disease: Role of Thyroid Hormone Triiodothyronine

by Francesca Forini^1,*, Giuseppina Nicolini^1,2 and Giorgio Iervasi¹

¹ CNR Institute of Clinical Physiology, Via G. Moruzzi 1, Pisa 56124, Italy

² Tuscany Region G. Monasterio Foundation, Via G. Moruzzi 1, Pisa 56124, Italy

Int. J. Mol. Sci. 2015, 16(3), 6312-6336; https://doi.org/10.3390/ijms16036312 - 19 Mar 2015

Cited by 47 | Viewed by 11542

Abstract

Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure [...] Read more.

Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure evolution. A growing body of experimental and clinical evidence show that the mitochondrion is an essential end effector of ischemia/ reperfusion injury and a major trigger of cell death in the acute ischemic phase (up to 48–72 h after the insult), the subacute phase (from 72 h to 7–10 days) and chronic stage (from 10–14 days to one month after the insult). As such, in recent years scientific efforts have focused on mitochondria as a target for cardioprotective strategies in ischemic heart disease and cardiomyopathy. The present review discusses recent advances in this field, with special emphasis on the emerging role of the biologically active thyroid hormone triiodothyronine (T3). Full article

(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)

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16 pages, 6024 KiB

Open AccessArticle

Supramolecular Cationic Assemblies against Multidrug-Resistant Microorganisms: Activity and Mechanism of Action

by Letícia Dias De Melo Carrasco^1,2, Jorge Luiz Mello Sampaio² and Ana Maria Carmona-Ribeiro^1,2,*

¹ Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Caixa Postal 26077, CEP 05513-970 São Paulo, Brazil

² Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil

Int. J. Mol. Sci. 2015, 16(3), 6337-6352; https://doi.org/10.3390/ijms16036337 - 19 Mar 2015

Cited by 30 | Viewed by 7092

Abstract

The growing challenge of antimicrobial resistance to antibiotics requires novel synthetic drugs or new formulations for old drugs. Here, cationic nanostructured particles (NPs) self-assembled from cationic bilayer fragments and polyelectrolytes are tested against four multidrug-resistant (MDR) strains of clinical importance. The non-hemolytic poly(diallyldimethylammonium) [...] Read more.

The growing challenge of antimicrobial resistance to antibiotics requires novel synthetic drugs or new formulations for old drugs. Here, cationic nanostructured particles (NPs) self-assembled from cationic bilayer fragments and polyelectrolytes are tested against four multidrug-resistant (MDR) strains of clinical importance. The non-hemolytic poly(diallyldimethylammonium) chloride (PDDA) polymer as the outer NP layer shows a remarkable activity against these organisms. The mechanism of cell death involves bacterial membrane lysis as determined from the leakage of inner phosphorylated compounds and possibly disassembly of the NP with the appearance of multilayered fibers made of the NP components and the biopolymers withdrawn from the cell wall. The NPs display broad-spectrum activity against MDR microorganisms, including Gram-negative and Gram-positive bacteria and yeast. Full article

(This article belongs to the Special Issue Supramolecular Interactions)

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20 pages, 1733 KiB

Open AccessReview

The Role of Hypoxia-Induced miR-210 in Cancer Progression

by Kyvan Dang and Kenneth A. Myers^*

Department of Biological Sciences, University of the Sciences, 600 S. 43rd Str., Philadelphia, PA 19104, USA

Int. J. Mol. Sci. 2015, 16(3), 6353-6372; https://doi.org/10.3390/ijms16036353 - 19 Mar 2015

Cited by 152 | Viewed by 9977

Abstract

Prolonged hypoxia, the event of insufficient oxygen, is known to upregulate tumor development and growth by promoting the formation of a neoplastic environment. The recent discovery that a subset of cellular microRNAs (miRs) are upregulated during hypoxia, where they function to promote tumor [...] Read more.

Prolonged hypoxia, the event of insufficient oxygen, is known to upregulate tumor development and growth by promoting the formation of a neoplastic environment. The recent discovery that a subset of cellular microRNAs (miRs) are upregulated during hypoxia, where they function to promote tumor development, highlights the importance of hypoxia-induced miRs as targets for continued investigation. miRs are short, non-coding transcripts involved in gene expression and regulation. Under hypoxic conditions, miR-210 becomes highly upregulated in response to hypoxia inducing factors (HIFs). HIF-1α drives miR-210’s overexpression and the resultant alteration of cellular processes, including cell cycle regulation, mitochondria function, apoptosis, angiogenesis and metastasis. Here we discuss hypoxia-induced dysregulation of miR-210 and the resultant changes in miR-210 protein targets that regulate cancer progression. Potential methods of targeting miR-210 as a therapeutic tool are also explored. Full article

(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)

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18 pages, 964 KiB

Open AccessArticle

SOD2 Activity Is not Impacted by Hyperoxia in Murine Neonatal Pulmonary Artery Smooth Muscle Cells and Mice

by Anita Gupta^†, Marta Perez^†, Keng Jin Lee, Joann M. Taylor and Kathryn N. Farrow^*

¹ Department of Pediatrics, Northwestern University Feinberg School of Medicine, 310 E. Superior St., Chicago, IL 60611, USA

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 6373-6390; https://doi.org/10.3390/ijms16036373 - 19 Mar 2015

Cited by 11 | Viewed by 6248

Abstract

Pulmonary hypertension (PH) complicates bronchopulmonary dysplasia (BPD) in 25% of infants. Superoxide dismutase 2 (SOD2) is an endogenous mitochondrial antioxidant, and overexpression protects against acute lung injury in adult mice. Little is known about SOD2 in neonatal lung disease and PH. C57Bl/6 mice [...] Read more.

Pulmonary hypertension (PH) complicates bronchopulmonary dysplasia (BPD) in 25% of infants. Superoxide dismutase 2 (SOD2) is an endogenous mitochondrial antioxidant, and overexpression protects against acute lung injury in adult mice. Little is known about SOD2 in neonatal lung disease and PH. C57Bl/6 mice and isogenic SOD2+/+ and SOD2−/+ mice were placed in room air (control) or 75% O₂ (chronic hyperoxia, CH) for 14 days. Right ventricular hypertrophy (RVH) was assessed by Fulton’s index. Medial wall thickness (MWT) and alveolar area were assessed on formalin fixed lung sections. Pulmonary artery smooth muscle cells (PASMC) were placed in 21% or 95% O₂ for 24 h. Lung and PASMC protein were analyzed for SOD2 expression and activity. Oxidative stress was measured with a mitochondrially-targeted sensor, mitoRoGFP. CH lungs have increased SOD2 expression, but unchanged activity. SOD2−/+ PASMC have decreased expression and activity at baseline, but increased SOD2 expression in hyperoxia. Hyperoxia increased mitochondrial ROS in SOD2+/+ and SOD2−/+ PASMC. SOD2+/+ and SOD2−/+ CH pups induced SOD2 expression, but not activity, and developed equivalent increases in RVH, MWT, and alveolar area. Since SOD2−/+ mice develop equivalent disease, this suggests other antioxidant systems may compensate for partial SOD2 expression and activity in the neonatal period during hyperoxia-induced oxidative stress. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)

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11 pages, 708 KiB

Open AccessArticle

Characterization and Antihyperglycemic Activity of a Polysaccharide from Dioscorea opposita Thunb Roots

by Yijun Fan^1,*,†, Qinyi He¹, Aoshuang Luo^2,†, Miaoyu Wang¹ and Aoxue Luo^1,*

¹ Department of Landscape Plants, Sichuan Agriculture University, Chengdu 611130, China

² Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 6391-6401; https://doi.org/10.3390/ijms16036391 - 19 Mar 2015

Cited by 62 | Viewed by 7722

Abstract

A polysaccharide DOTP-80 from Dioscorea opposita Thunb was obtained by using the method of acid water-extraction and ethanol-precipitation. After being purified by chromatography, the structure characteristics of DOTP-80 were established. Based on the calibration curve obtained with standard dextrans, the molecular weight of [...] Read more.

A polysaccharide DOTP-80 from Dioscorea opposita Thunb was obtained by using the method of acid water-extraction and ethanol-precipitation. After being purified by chromatography, the structure characteristics of DOTP-80 were established. Based on the calibration curve obtained with standard dextrans, the molecular weight of the polysaccharide fraction DOTP-80 was calculated to be 123 kDa. The results of Infrared spectrum (FT-IR) indicated that the polysaccharide contained the α-configuration of sugar units. GC-MS analysis revealed that DOTP-80 was mainly composed of mannose and glucose. Alloxan-induced diabetic rats and mice models were developed to evaluate the in vivo hypoglycemic activity of the polysaccharide. The results indicated that a high dose DOTP-80 (400 mg/kg) had strong hypoglycemic activity. Moreover, DOTP-80 could increase the level of antioxidant enzymes (SOD) activity in alloxan-induced diabetic mice and stimulate an increase in glucose disposal in diabetic rats. Therefore, the polysaccharide DOTP-80 should be evaluated as a candidate for future studies on diabetes mellitus. Full article

(This article belongs to the Special Issue Bioactive Carbohydrates and Peptides)

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17 pages, 5608 KiB

Open AccessArticle

Exploring the Nature of Silicon-Noble Gas Bonds in H₃SiNgNSi and HSiNgNSi Compounds (Ng = Xe, Rn)

by Sudip Pan, Ranajit Saha and Pratim K. Chattaraj^*

Department of Chemistry and Centre for Theoretical Studies, Indian Institute of Technology, Kharagpur 721302, India

Int. J. Mol. Sci. 2015, 16(3), 6402-6418; https://doi.org/10.3390/ijms16036402 - 19 Mar 2015

Cited by 39 | Viewed by 7939

Abstract

Ab initio and density functional theory-based computations are performed to investigate the structure and stability of H₃SiNgNSi and HSiNgNSi compounds (Ng = Xe, Rn). They are thermochemically unstable with respect to the dissociation channel producing Ng and H₃SiNSi or [...] Read more.

Ab initio and density functional theory-based computations are performed to investigate the structure and stability of H₃SiNgNSi and HSiNgNSi compounds (Ng = Xe, Rn). They are thermochemically unstable with respect to the dissociation channel producing Ng and H₃SiNSi or HSiNSi. However, they are kinetically stable with respect to this dissociation channel having activation free energy barriers of 19.3 and 23.3 kcal/mol for H₃SiXeNSi and H₃SiRnNSi, respectively, and 9.2 and 12.8 kcal/mol for HSiXeNSi and HSiRnNSi, respectively. The rest of the possible dissociation channels are endergonic in nature at room temperature for Rn analogues. However, one three-body dissociation channel for H₃SiXeNSi and one two-body and one three-body dissociation channels for HSiXeNSi are slightly exergonic in nature at room temperature. They become endergonic at slightly lower temperature. The nature of bonding between Ng and Si/N is analyzed by natural bond order, electron density and energy decomposition analyses. Natural population analysis indicates that they could be best represented as (H₃SiNg)⁺(NSi)⁻ and (HSiNg)⁺(NSi)⁻. Energy decomposition analysis further reveals that the contribution from the orbital term (ΔE_orb) is dominant (ca. 67%–75%) towards the total attraction energy associated with the Si-Ng bond, whereas the electrostatic term (ΔE_elstat) contributes the maximum (ca. 66%–68%) for the same in the Ng–N bond, implying the covalent nature of the former bond and the ionic nature of the latter. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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13 pages, 1489 KiB

Open AccessReview

Wilson’s Disease: A Comprehensive Review of the Molecular Mechanisms

by Fei Wu^1,†, Jing Wang^2,†, Chunwen Pu³, Liang Qiao^4,* and Chunmeng Jiang^2,*

¹ Department of imaging, the Affiliated Zhongshan Hospital of Dalian University, 6 Jiefang Street, Zhongshan District, Dalian 116001, Liaoning, China

² Department of Internal Medicine, the Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian 116023, Liaoning, China

³ Department of Biobank, the Sixth People's Hospital of Dalian, 269 Luganghuibai Road, Ganjingzi District, Dalian 116031, Liaoning, China

⁴ Storr Liver Centre, Westmead Millennium Institute for Medical Research, Faculty of Medicine, the University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 6419-6431; https://doi.org/10.3390/ijms16036419 - 20 Mar 2015

Cited by 99 | Viewed by 25967

Abstract

Wilson’s disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder resulting from abnormal copper metabolism. Reduced copper excretion causes an excessive deposition of the copper in many organs such as the liver, central nervous system (CNS), cornea, kidney, joints, [...] Read more.

Wilson’s disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder resulting from abnormal copper metabolism. Reduced copper excretion causes an excessive deposition of the copper in many organs such as the liver, central nervous system (CNS), cornea, kidney, joints, and cardiac muscle where the physiological functions of the affected organs are impaired. The underlying molecular mechanisms for WD have been extensively studied. It is now believed that a defect in P-type adenosine triphosphatase (ATP7B), the gene encoding the copper transporting P-type ATPase, is responsible for hepatic copper accumulation. Deposited copper in the liver produces toxic effects via modulating several molecular pathways. WD can be a lethal disease if left untreated. A better understanding of the molecular mechanisms causing the aberrant copper deposition and organ damage is the key to developing effective management approaches. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)

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15 pages, 786 KiB

Open AccessReview

Primary Biliary Cirrhosis Is a Generalized Autoimmune Epithelitis

by Jun Gao¹, Liang Qiao² and Bingyuan Wang^1,*

¹ Department of Geriatric Gastroenterology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China

² Storr Liver Centre, Westmead Millennium Institute for Medical Research, the University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia

Int. J. Mol. Sci. 2015, 16(3), 6432-6446; https://doi.org/10.3390/ijms16036432 - 20 Mar 2015

Cited by 10 | Viewed by 9745

Abstract

Primary biliary cirrhosis (PBC) is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs) and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs) may contribute to apotope presentation to [...] Read more.

Primary biliary cirrhosis (PBC) is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs) and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs) may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)

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17 pages, 1907 KiB

Open AccessArticle

Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response

by Sina Kühne, Wymke Ockenga, Antje Banning and Ritva Tikkanen^*

Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, D-35392 Giessen, Germany

Int. J. Mol. Sci. 2015, 16(3), 6447-6463; https://doi.org/10.3390/ijms16036447 - 20 Mar 2015

Cited by 10 | Viewed by 7020

Abstract

Acetylcholine and its receptors regulate numerous cellular processes in keratinocytes and other non-neuronal cells. Muscarinic acetylcholine receptors are capable of transactivating the epidermal growth factor receptor (EGFR) and, downstream thereof, the mitogen-activated protein kinase (MAPK) cascade, which in turn regulates transcription of genes [...] Read more.

Acetylcholine and its receptors regulate numerous cellular processes in keratinocytes and other non-neuronal cells. Muscarinic acetylcholine receptors are capable of transactivating the epidermal growth factor receptor (EGFR) and, downstream thereof, the mitogen-activated protein kinase (MAPK) cascade, which in turn regulates transcription of genes involved in cell proliferation and migration. We here show that cholinergic stimulation of human HaCaT keratinocytes results in increased transcription of matrix metalloproteinase MMP-3 as well as several ligands of the epidermal growth factor family. Since both metalloproteinases and the said ligands are involved in the transactivation of the EGFR, this transcriptional upregulation may provide a positive feed-forward loop for EGFR/MAPK activation. We here also show that the cholinergic EGFR and MAPK activation and the upregulation of MMP-3 and EGF-like ligands are dependent on the expression of flotillin-1 which we have previously shown to be a regulator of MAPK signaling. Full article

(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)

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32 pages, 1773 KiB

Open AccessArticle

High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders

by Merlin G. Butler^*

, Syed K. Rafi^† and Ann M. Manzardo^†

¹ Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA

^† These authors contributed to this work equally.

Int. J. Mol. Sci. 2015, 16(3), 6464-6495; https://doi.org/10.3390/ijms16036464 - 20 Mar 2015

Cited by 53 | Viewed by 18995

Abstract

Recently, autism-related research has focused on the identification of various genes and disturbed pathways causing the genetically heterogeneous group of autism spectrum disorders (ASD). The list of autism-related genes has significantly increased due to better awareness with advances in genetic technology and expanding [...] Read more.

Recently, autism-related research has focused on the identification of various genes and disturbed pathways causing the genetically heterogeneous group of autism spectrum disorders (ASD). The list of autism-related genes has significantly increased due to better awareness with advances in genetic technology and expanding searchable genomic databases. We compiled a master list of known and clinically relevant autism spectrum disorder genes identified with supporting evidence from peer-reviewed medical literature sources by searching key words related to autism and genetics and from authoritative autism-related public access websites, such as the Simons Foundation Autism Research Institute autism genomic database dedicated to gene discovery and characterization. Our list consists of 792 genes arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms, thereby enabling clinical and laboratory geneticists and genetic counsellors to access convenient visual images of the location and distribution of ASD genes. Meaningful correlations of the observed phenotype in patients with suspected/confirmed ASD gene(s) at the chromosome region or breakpoint band site can be made to inform diagnosis and gene-based personalized care and provide genetic counselling for families. Full article

(This article belongs to the Special Issue The Identification of the Genetic Components of Autism Spectrum Disorders)

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17 pages, 1012 KiB

Open AccessArticle

Favourable IFNL3 Genotypes Are Associated with Spontaneous Clearance and Are Differentially Distributed in Aboriginals in Canadian HIV-Hepatitis C Co-Infected Individuals

by Nasheed Moqueet¹, Claire Infante-Rivard¹, Robert W. Platt¹, Jim Young^2,3, Curtis Cooper⁴, Mark Hull⁵, Sharon Walmsley⁶, Marina B. Klein^1,3,* and The Canadian Co-Infection Study Investigators⁷

¹ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada

² Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel 4031, Switzerland

³ Department of Medicine, Division of Infectious Diseases/Chronic Viral Illness Service, Royal Victoria Hospital, McGill University Health Centre, 3650 Saint-Urbain Street, Montreal, QC H2X 2P4, Canada

⁴ The Ottawa Hospital—Research Institute, Ottawa, ON K1Y 4E9, Canada

⁵ BC Centre for Excellence in HIV/AIDS, Vancouver, BC V6Z 1Y6, Canada

⁶ Toronto General Research Institute, University Health Network, University of Toronto, Toronto, ON M5G 2M9, Canada

⁷ The Canadian Co-Infection Study Investigators (see Appendix)

Int. J. Mol. Sci. 2015, 16(3), 6496-6512; https://doi.org/10.3390/ijms16036496 - 20 Mar 2015

Cited by 6 | Viewed by 6720

Abstract

Canadian Aboriginals are reported to clear Hepatitis C (HCV) more frequently. We tested the association of spontaneous clearance and three single nucleotide polymorphisms (SNPs) near the Interferon-lambda 3 (IFNL3) gene (rs12979860, rs8099917, functional variant rs8103142) and compared the SNP frequencies between HIV-HCV co-infected [...] Read more.

Canadian Aboriginals are reported to clear Hepatitis C (HCV) more frequently. We tested the association of spontaneous clearance and three single nucleotide polymorphisms (SNPs) near the Interferon-lambda 3 (IFNL3) gene (rs12979860, rs8099917, functional variant rs8103142) and compared the SNP frequencies between HIV-HCV co-infected whites and Aboriginals from the Canadian Co-infection Cohort. HCV treatment-naïve individuals with at least two HCV RNA tests were included (n = 538). A spontaneous clearance case was defined as someone with two consecutive HCV RNA-negative tests, at least six months apart. Data were analyzed using Cox proportional hazards adjusted for sex and ethnicity. Advantageous variants and haplotypes were more common in Aboriginals than Caucasians: 57% vs. 46% had the rs12979860 CC genotype, respectively; 58% vs. 48%, rs8103142 TT; 74% vs. 67%, the rs12979860 C allele; and 67% vs. 64% the TCT haplotype with three favourable alleles. The adjusted Hazard Ratios (95% CI) for spontaneous clearance were: rs12979860: 3.80 (2.20, 6.54); rs8099917: 5.14 (2.46, 10.72); and rs8103142: 4.36 (2.49, 7.62). Even after adjusting for rs12979860, Aboriginals and females cleared HCV more often, HR (95% CI) = 1.53 (0.89, 2.61) and 1.42 (0.79, 2.53), respectively. Our results suggest that favourable IFNL3 genotypes are more common among Aboriginals than Caucasians, and may partly explain the higher HCV clearance rates seen among Aboriginals. Full article

(This article belongs to the Special Issue Viral Hepatitis Research)

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19 pages, 2092 KiB

Open AccessReview

Recent Developments of Engineered Translational Machineries for the Incorporation of Non-Canonical Amino Acids into Polypeptides

by Naohiro Terasaka¹, Yoshihiko Iwane¹, Anna-Skrollan Geiermann¹, Yuki Goto¹ and Hiroaki Suga^1,2,*

¹ Department of Chemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

² Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Int. J. Mol. Sci. 2015, 16(3), 6513-6531; https://doi.org/10.3390/ijms16036513 - 20 Mar 2015

Cited by 30 | Viewed by 12419

Abstract

Genetic code expansion and reprogramming methodologies allow us to incorporate non-canonical amino acids (ncAAs) bearing various functional groups, such as fluorescent groups, bioorthogonal functional groups, and post-translational modifications, into a desired position or multiple positions in polypeptides both in vitro and in vivo [...] Read more.

Genetic code expansion and reprogramming methodologies allow us to incorporate non-canonical amino acids (ncAAs) bearing various functional groups, such as fluorescent groups, bioorthogonal functional groups, and post-translational modifications, into a desired position or multiple positions in polypeptides both in vitro and in vivo. In order to efficiently incorporate a wide range of ncAAs, several methodologies have been developed, such as orthogonal aminoacyl-tRNA-synthetase (AARS)–tRNA pairs, aminoacylation ribozymes, frame-shift suppression of quadruplet codons, and engineered ribosomes. More recently, it has been reported that an engineered translation system specifically utilizes an artificially built genetic code and functions orthogonally to naturally occurring counterpart. In this review we summarize recent advances in the field of ribosomal polypeptide synthesis containing ncAAs. Full article

(This article belongs to the Special Issue Functions of Transfer RNAs)

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13 pages, 1741 KiB

Open AccessArticle

Discovery of Benzo[f]indole-4,9-dione Derivatives as New Types of Anti-Inflammatory Agents

by You-Ren Chen¹, Chih-Hua Tseng²

, Yeh-Long Chen¹, Tsong-Long Hwang^3,4,*

and Cherng-Chyi Tzeng^1,*

¹ Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan

² School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

³ Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan

⁴ Immunology Consortium, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan

Int. J. Mol. Sci. 2015, 16(3), 6532-6544; https://doi.org/10.3390/ijms16036532 - 23 Mar 2015

Cited by 21 | Viewed by 5975

Abstract

Certain benzo[f]indole-4,9-dione derivatives were synthesized and evaluated for their inhibitory effects on superoxide anion generation and neutrophil elastase (NE) release in formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils. Results indicated that (Z)-1-benzyl-4-(hydroxyimino)-1H-benzo[f]indol-9(4H)-one (10) showed [...] Read more.

Certain benzo[f]indole-4,9-dione derivatives were synthesized and evaluated for their inhibitory effects on superoxide anion generation and neutrophil elastase (NE) release in formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils. Results indicated that (Z)-1-benzyl-4-(hydroxyimino)-1H-benzo[f]indol-9(4H)-one (10) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC₅₀ value of 2.78 and 2.74 μM respectively. The action mechanisms of 10 in human neutrophils were further investigated. Our results showed that compound 10 did not alter fMLF-induced phosphorylation of Src (Src family Y416). Notably, phosphorylation of Akt (S473) and mobilization of [Ca²⁺]_i caused by fMLF was inhibited by compound 10. Further structural optimization of 10 is ongoing. Full article

(This article belongs to the Section Biochemistry)

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12 pages, 1382 KiB

Open AccessReview

The Potential of the Combination of CRISPR/Cas9 and Pluripotent Stem Cells to Provide Human Organs from Chimaeric Pigs

by Wanyou Feng¹, Yifan Dai², Lisha Mou^1,*, David K. C. Cooper³, Deshun Shi⁴ and Zhiming Cai^1,*

¹ Shenzhen Key Laboratory of Xenotransplantaton, State and Local Joint Cancer Genome Clinical Application of Key Technology Laboratory, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518039, China

² Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 210029, China

³ Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA

⁴ State Key Laboratory of Conservation & Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China

Int. J. Mol. Sci. 2015, 16(3), 6545-6556; https://doi.org/10.3390/ijms16036545 - 23 Mar 2015

Cited by 31 | Viewed by 16819

Abstract

Clinical organ allotransplantation is limited by the availability of deceased human donors. However, the transplantation of human organs produced in other species would provide an unlimited number of organs. The pig has been identified as the most suitable source of organs for humans [...] Read more.

Clinical organ allotransplantation is limited by the availability of deceased human donors. However, the transplantation of human organs produced in other species would provide an unlimited number of organs. The pig has been identified as the most suitable source of organs for humans as organs of any size would be available. Genome editing by RNA-guided endonucleases, also known as clustered regularly interspaced short palindromic repeat (CRISPR/Cas9), in combination with induced pluripotent stem cells (iPSC), may have the potential to enable the creation of human organs from genetically-modified chimaeric pigs. These could potentially provide an unlimited supply of organs that would not be rejected by the recipient’s immune system. However, substantial research is needed to prove that this approach will work. Genetic modification of chimaeric pigs could also provide useful models for developing therapies for various human diseases, especially in relation to drug development. Full article

(This article belongs to the Special Issue Genome Editing)

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14 pages, 2215 KiB

Open AccessReview

Amniotic Fluid Embolism Pathophysiology Suggests the New Diagnostic Armamentarium: β-Tryptase and Complement Fractions C3-C4 Are the Indispensable Working Tools

by Francesco Paolo Busardò¹, Paola Frati^1,2, Simona Zaami¹ and Vittorio Fineschi^1,*

¹ Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy

² Neuromed, Istituto Mediterraneo Neurologico (IRCCS), Via Atinense 18, Pozzilli, 86077 Isernia, Italy

Int. J. Mol. Sci. 2015, 16(3), 6557-6570; https://doi.org/10.3390/ijms16036557 - 23 Mar 2015

Cited by 40 | Viewed by 17891

Abstract

Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving pregnant women during labor or in the initial stages after delivery. Its incidence is estimated to be around 5.5 cases per 100,000 deliveries. Therefore, this paper investigated the pathophysiological mechanism, which underlies AFE, [...] Read more.

Amniotic fluid embolism (AFE) is an uncommon obstetric condition involving pregnant women during labor or in the initial stages after delivery. Its incidence is estimated to be around 5.5 cases per 100,000 deliveries. Therefore, this paper investigated the pathophysiological mechanism, which underlies AFE, in order to evaluate the role of immune response in the development of this still enigmatic clinical entity. The following databases (from 1956 to September 2014) Medline, Cochrane Central, Scopus, Web of Science and Science Direct were used, searching the following key words: AFE, pathophysiology, immune/inflammatory response, complement and anaphylaxis. The main key word “AFE” was searched singularly and associated individually to each of the other keywords. Of the 146 sources found, only 19 were considered appropriate for the purpose of this paper. The clinical course is characterized by a rapid onset of symptoms, which include: acute hypotension and/or cardiac arrest, acute hypoxia (with dyspnoea, cyanosis and/or respiratory arrest), coagulopathies (disseminated intravascular coagulation and/or severe hemorrhage), coma and seizures. The pathology still determines a significant morbidity and mortality and potential permanent neurological sequelae for surviving patients. At this moment, numerous aspects involving the pathophysiology and clinical development are still not understood and several hypotheses have been formulated, in particular the possible role of anaphylaxis and complement. Moreover, the detection of serum tryptase and complement components and the evaluation of fetal antigens can explain several aspects of immune response. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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24 pages, 2025 KiB

Open AccessReview

Aminoacyl-tRNA Synthetase Complexes in Evolution

by Svitlana Havrylenko^1,† and Marc Mirande^1,2,*

¹ Laboratoire d'Enzymologie et Biochimie Structurales (LEBS), CNRS, Université Paris-Sud, 1 avenue de la Terrasse, 91190 Gif-sur-Yvette, France

² Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, 1 avenue de la Terrasse, 91190 Gif-sur-Yvette, France

^† Present address: Institut Curie, CNRS UMR 168, Université Pierre et Marie Curie, 75248 Paris, France

Int. J. Mol. Sci. 2015, 16(3), 6571-6594; https://doi.org/10.3390/ijms16036571 - 23 Mar 2015

Cited by 53 | Viewed by 11970

Abstract

Aminoacyl-tRNA synthetases are essential enzymes for interpreting the genetic code. They are responsible for the proper pairing of codons on mRNA with amino acids. In addition to this canonical, translational function, they are also involved in the control of many cellular pathways essential [...] Read more.

Aminoacyl-tRNA synthetases are essential enzymes for interpreting the genetic code. They are responsible for the proper pairing of codons on mRNA with amino acids. In addition to this canonical, translational function, they are also involved in the control of many cellular pathways essential for the maintenance of cellular homeostasis. Association of several of these enzymes within supramolecular assemblies is a key feature of organization of the translation apparatus in eukaryotes. It could be a means to control their oscillation between translational functions, when associated within a multi-aminoacyl-tRNA synthetase complex (MARS), and nontranslational functions, after dissociation from the MARS and association with other partners. In this review, we summarize the composition of the different MARS described from archaea to mammals, the mode of assembly of these complexes, and their roles in maintenance of cellular homeostasis. Full article

(This article belongs to the Special Issue Functions of Transfer RNAs)

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11 pages, 1891 KiB

Open AccessArticle

Activity Analysis and Preliminary Inducer Screening of the Chicken DAZL Gene Promoter

by Lei Zhang^†, Rui Zhu^†, Qisheng Zuo, Dong Li, Chao Lian, Beibei Tang, Tianrong Xiao, Yani Zhang and Bichun Li^*

¹ College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, Jiangsu, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(3), 6595-6605; https://doi.org/10.3390/ijms16036595 - 23 Mar 2015

Cited by 6 | Viewed by 6244

Abstract

This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter [...] Read more.

This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase^® Reporter Assay System was used to identify the activity of the DAZL gene under different inducers. Our studies showed that the DAZL core promoter region for the Suqin yellow chicken was −383 to −39 bp. The dual-luciferase^® reporter showed that all-trans retinoic acid (ATRA), a retinoic acid receptor alpha agonist (tamibarotene/Am80), or estradiol (E₂) could significantly enhance DAZL transcription. The in vitro inductive culture of chicken ESCs demonstrated that, with ATRA treatment, DAZL transcription peaked at 6 days and then decreased slowly; whereas, DAZL transcription was continuous and peaked at 10 days with Am80 treatment. E₂ treatment significantly increased DAZL expression after 8 days. All three treatments were associated with the appearance of male germ cell (MGC)-like cells on day 10. These results provide the optimum inducer screening of the DAZL gene and lay the foundation for further screening of compounds that can induce the differentiation of ESCs into MGCs in vitro. Full article

(This article belongs to the Section Biochemistry)

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Int. J. Mol. Sci., Volume 16, Issue 3 (March 2015) – 128 articles , Pages 4362-6620

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