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Int. J. Mol. Sci., Volume 16, Issue 3 (March 2015) – 128 articles , Pages 4362-6620

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798 KiB  
Review
Coronary Artery Calcium Screening: Does it Perform Better than Other Cardiovascular Risk Stratification Tools?
by Irfan Zeb and Matthew Budoff
Int. J. Mol. Sci. 2015, 16(3), 6606-6620; https://doi.org/10.3390/ijms16036606 - 23 Mar 2015
Cited by 32 | Viewed by 6601
Abstract
Coronary artery calcium (CAC) has been advocated as one of the strongest cardiovascular risk prediction markers. It performs better across a wide range of Framingham risk categories (6%–10% and 10%–20% 10-year risk categories) and also helps in reclassifying the risk of these subjects [...] Read more.
Coronary artery calcium (CAC) has been advocated as one of the strongest cardiovascular risk prediction markers. It performs better across a wide range of Framingham risk categories (6%–10% and 10%–20% 10-year risk categories) and also helps in reclassifying the risk of these subjects into either higher or lower risk categories based on CAC scores. It also performs better among population subgroups where Framingham risk score does not perform well, especially young subjects, women, family history of premature coronary artery disease and ethnic differences in coronary risk. The absence of CAC is also associated with excellent prognosis, with 10-year event rate of 1%. Studies have also compared with other commonly used markers of cardiovascular disease risk such as Carotid intima-media thickness and highly sensitive C-reactive protein. CAC also performs better compared with carotid intima-media thickness and highly sensitive C-reactive protein in prediction of coronary heart disease and cardiovascular disease events. CAC scans are associated with relatively low radiation exposure (0.9–1.1 mSv) and provide information that can be used not only for risk stratification but also can be used to track the progression of atherosclerosis and the effects of statins. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)
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1891 KiB  
Article
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
Int. J. Mol. Sci. 2015, 16(3), 6595-6605; https://doi.org/10.3390/ijms16036595 - 23 Mar 2015
Cited by 5 | Viewed by 5596
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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Review
Aminoacyl-tRNA Synthetase Complexes in Evolution
by Svitlana Havrylenko and Marc Mirande
Int. J. Mol. Sci. 2015, 16(3), 6571-6594; https://doi.org/10.3390/ijms16036571 - 23 Mar 2015
Cited by 47 | Viewed by 10448
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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Review
Amniotic Fluid Embolism Pathophysiology Suggests the New Diagnostic Armamentarium: β-Tryptase and Complement Fractions C3-C4 Are the Indispensable Working Tools
by Francesco Paolo Busardò, Paola Frati, Simona Zaami and Vittorio Fineschi
Int. J. Mol. Sci. 2015, 16(3), 6557-6570; https://doi.org/10.3390/ijms16036557 - 23 Mar 2015
Cited by 27 | Viewed by 15593
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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Review
The Potential of the Combination of CRISPR/Cas9 and Pluripotent Stem Cells to Provide Human Organs from Chimaeric Pigs
by Wanyou Feng, Yifan Dai, Lisha Mou, David K. C. Cooper, Deshun Shi and Zhiming Cai
Int. J. Mol. Sci. 2015, 16(3), 6545-6556; https://doi.org/10.3390/ijms16036545 - 23 Mar 2015
Cited by 29 | Viewed by 15198
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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Article
Discovery of Benzo[f]indole-4,9-dione Derivatives as New Types of Anti-Inflammatory Agents
by You-Ren Chen, Chih-Hua Tseng, Yeh-Long Chen, Tsong-Long Hwang and Cherng-Chyi Tzeng
Int. J. Mol. Sci. 2015, 16(3), 6532-6544; https://doi.org/10.3390/ijms16036532 - 23 Mar 2015
Cited by 15 | Viewed by 5290
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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2092 KiB  
Review
Recent Developments of Engineered Translational Machineries for the Incorporation of Non-Canonical Amino Acids into Polypeptides
by Naohiro Terasaka, Yoshihiko Iwane, Anna-Skrollan Geiermann, Yuki Goto and Hiroaki Suga
Int. J. Mol. Sci. 2015, 16(3), 6513-6531; https://doi.org/10.3390/ijms16036513 - 20 Mar 2015
Cited by 29 | Viewed by 11184
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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Article
Favourable IFNL3 Genotypes Are Associated with Spontaneous Clearance and Are Differentially Distributed in Aboriginals in Canadian HIV-Hepatitis C Co-Infected Individuals
by Nasheed Moqueet, Claire Infante-Rivard, Robert W. Platt, Jim Young, Curtis Cooper, Mark Hull, Sharon Walmsley, Marina B. Klein and The Canadian Co-Infection Study Investigators
Int. J. Mol. Sci. 2015, 16(3), 6496-6512; https://doi.org/10.3390/ijms16036496 - 20 Mar 2015
Cited by 5 | Viewed by 6086
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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Article
High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders
by Merlin G. Butler, Syed K. Rafi and Ann M. Manzardo
Int. J. Mol. Sci. 2015, 16(3), 6464-6495; https://doi.org/10.3390/ijms16036464 - 20 Mar 2015
Cited by 41 | Viewed by 15802
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
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Article
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
Int. J. Mol. Sci. 2015, 16(3), 6447-6463; https://doi.org/10.3390/ijms16036447 - 20 Mar 2015
Cited by 10 | Viewed by 6303
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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786 KiB  
Review
Primary Biliary Cirrhosis Is a Generalized Autoimmune Epithelitis
by Jun Gao, Liang Qiao and Bingyuan Wang
Int. J. Mol. Sci. 2015, 16(3), 6432-6446; https://doi.org/10.3390/ijms16036432 - 20 Mar 2015
Cited by 7 | Viewed by 8847
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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Review
Wilson’s Disease: A Comprehensive Review of the Molecular Mechanisms
by Fei Wu, Jing Wang, Chunwen Pu, Liang Qiao and Chunmeng Jiang
Int. J. Mol. Sci. 2015, 16(3), 6419-6431; https://doi.org/10.3390/ijms16036419 - 20 Mar 2015
Cited by 81 | Viewed by 21368
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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Article
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
Int. J. Mol. Sci. 2015, 16(3), 6402-6418; https://doi.org/10.3390/ijms16036402 - 19 Mar 2015
Cited by 36 | Viewed by 7059
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 (ΔEorb) is dominant (ca. 67%–75%) towards the total attraction energy associated with the Si-Ng bond, whereas the electrostatic term (ΔEelstat) 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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Article
Characterization and Antihyperglycemic Activity of a Polysaccharide from Dioscorea opposita Thunb Roots
by Yijun Fan, Qinyi He, Aoshuang Luo, Miaoyu Wang and Aoxue Luo
Int. J. Mol. Sci. 2015, 16(3), 6391-6401; https://doi.org/10.3390/ijms16036391 - 19 Mar 2015
Cited by 49 | Viewed by 6588
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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Article
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
Int. J. Mol. Sci. 2015, 16(3), 6373-6390; https://doi.org/10.3390/ijms16036373 - 19 Mar 2015
Cited by 11 | Viewed by 5568
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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Review
The Role of Hypoxia-Induced miR-210 in Cancer Progression
by Kyvan Dang and Kenneth A. Myers
Int. J. Mol. Sci. 2015, 16(3), 6353-6372; https://doi.org/10.3390/ijms16036353 - 19 Mar 2015
Cited by 136 | Viewed by 8312
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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Article
Supramolecular Cationic Assemblies against Multidrug-Resistant Microorganisms: Activity and Mechanism of Action
by Letícia Dias De Melo Carrasco, Jorge Luiz Mello Sampaio and Ana Maria Carmona-Ribeiro
Int. J. Mol. Sci. 2015, 16(3), 6337-6352; https://doi.org/10.3390/ijms16036337 - 19 Mar 2015
Cited by 26 | Viewed by 6365
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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843 KiB  
Review
Mitochondria as Key Targets of Cardioprotection in Cardiac Ischemic Disease: Role of Thyroid Hormone Triiodothyronine
by Francesca Forini, Giuseppina Nicolini and Giorgio Iervasi
Int. J. Mol. Sci. 2015, 16(3), 6312-6336; https://doi.org/10.3390/ijms16036312 - 19 Mar 2015
Cited by 44 | Viewed by 9650
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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Article
Genotyping Test with Clinical Factors: Better Management of Acute Postoperative Pain?
by Aline Hajj, Katell Peoc'h, Jean-Louis Laplanche, Hicham Jabbour, Nicole Naccache, Hicham Abou Zeid, Patricia Yazbeck and Lydia Rabbaa Khabbaz
Int. J. Mol. Sci. 2015, 16(3), 6298-6311; https://doi.org/10.3390/ijms16036298 - 19 Mar 2015
Cited by 12 | Viewed by 5783
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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Review
Role of Pancreatic Transcription Factors in Maintenance of Mature β-Cell Function
by Hideaki Kaneto and Taka-aki Matsuoka
Int. J. Mol. Sci. 2015, 16(3), 6281-6297; https://doi.org/10.3390/ijms16036281 - 18 Mar 2015
Cited by 54 | Viewed by 9654
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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Article
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, Xiangyun Chen, Xiaofang Tang, Chundong Zhang, La Wang, Peng Chen, Minhui Pan and Cheng Lu
Int. J. Mol. Sci. 2015, 16(3), 6266-6280; https://doi.org/10.3390/ijms16036266 - 18 Mar 2015
Cited by 11 | Viewed by 6810
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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Article
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 Lee, Young-Min Park, Seung-Hwan Lee and Miseon Shim
Int. J. Mol. Sci. 2015, 16(3), 6251-6265; https://doi.org/10.3390/ijms16036251 - 18 Mar 2015
Cited by 30 | Viewed by 6117
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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Article
Abortive Infection of Snakehead Fish Vesiculovirus in ZF4 Cells Was Associated with the RLRs Pathway Activation by Viral Replicative Intermediates
by Wenwen Wang, Muhammad Asim, Lizhu Yi, Abeer M. Hegazy, Xianqin Hu, Yang Zhou, Taoshan Ai and Li Lin
Int. J. Mol. Sci. 2015, 16(3), 6235-6250; https://doi.org/10.3390/ijms16036235 - 18 Mar 2015
Cited by 25 | Viewed by 7161
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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Article
Molecular Dynamics Simulations of Acylpeptide Hydrolase Bound to Chlorpyrifosmethyl Oxon and Dichlorvos
by Hanyong Jin, Zhenhuan Zhou, Dongmei Wang, Shanshan Guan and Weiwei Han
Int. J. Mol. Sci. 2015, 16(3), 6217-6234; https://doi.org/10.3390/ijms16036217 - 18 Mar 2015
Cited by 19 | Viewed by 6258
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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Article
Effect of Chemical Treatments on Flax Fibre Reinforced Polypropylene Composites on Tensile and Dome Forming Behaviour
by Wentian Wang, Adrian Lowe and Shankar Kalyanasundaram
Int. J. Mol. Sci. 2015, 16(3), 6202-6216; https://doi.org/10.3390/ijms16036202 - 17 Mar 2015
Cited by 9 | Viewed by 4389
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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Review
DNA Damage: A Sensible Mediator of the Differentiation Decision in Hematopoietic Stem Cells and in Leukemia
by Cary N. Weiss and Keisuke Ito
Int. J. Mol. Sci. 2015, 16(3), 6183-6201; https://doi.org/10.3390/ijms16036183 - 17 Mar 2015
Cited by 26 | Viewed by 8982
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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Review
New Therapies for Dedifferentiated Papillary Thyroid Cancer
by Poupak Fallahi, Valeria Mazzi, Roberto Vita, Silvia Martina Ferrari, Gabriele Materazzi, David Galleri, Salvatore Benvenga, Paolo Miccoli and Alessandro Antonelli
Int. J. Mol. Sci. 2015, 16(3), 6153-6182; https://doi.org/10.3390/ijms16036153 - 17 Mar 2015
Cited by 44 | Viewed by 9070
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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Article
Polyoxygenated Cembrane Diterpenoids from the Soft Coral Sarcophyton ehrenbergi
by Shi-Yie Cheng, Shang-Kwei Wang, Mu-Keng Hsieh and Chang-Yih Duh
Int. J. Mol. Sci. 2015, 16(3), 6140-6152; https://doi.org/10.3390/ijms16036140 - 17 Mar 2015
Cited by 14 | Viewed by 4956
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 15 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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Review
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
Int. J. Mol. Sci. 2015, 16(3), 6124-6139; https://doi.org/10.3390/ijms16036124 - 17 Mar 2015
Cited by 38 | Viewed by 8252
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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Article
In Vitro Corrosion and Cytocompatibility Properties of Nano-Whisker Hydroxyapatite Coating on Magnesium Alloy for Bone Tissue Engineering Applications
by Huawei Yang, Xueyu Yan, Min Ling, Zuquan Xiong, Caiwen Ou and Wei Lu
Int. J. Mol. Sci. 2015, 16(3), 6113-6123; https://doi.org/10.3390/ijms16036113 - 17 Mar 2015
Cited by 20 | Viewed by 6206
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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