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Int. J. Mol. Sci., Volume 19, Issue 12 (December 2018)

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Open AccessArticle The Arabidopsis Ca2+-Dependent Protein Kinase CPK12 Is Involved in Plant Response to Salt Stress
Int. J. Mol. Sci. 2018, 19(12), 4062; https://doi.org/10.3390/ijms19124062 (registering DOI)
Received: 1 December 2018 / Revised: 11 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
CDPKs (Ca2+-Dependent Protein Kinases) are very important regulators in plant response to abiotic stress. The molecular regulatory mechanism of CDPKs involved in salt stress tolerance remains unclear, although some CDPKs have been identified in salt-stress signaling. Here, we investigated the function
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CDPKs (Ca2+-Dependent Protein Kinases) are very important regulators in plant response to abiotic stress. The molecular regulatory mechanism of CDPKs involved in salt stress tolerance remains unclear, although some CDPKs have been identified in salt-stress signaling. Here, we investigated the function of an Arabidopsis CDPK, CPK12, in salt-stress signaling. The CPK12-RNA interference (RNAi) mutant was much more sensitive to salt stress than the wild-type plant GL1 in terms of seedling growth. Under NaCl treatment, Na+ levels in the roots of CPK12-RNAi plants increased and were higher than levels in GL1 plants. In addition, the level of salt-elicited H2O2 production was higher in CPK12-RNAi mutants than in wild-type GL1 plants after NaCl treatment. Collectively, our results suggest that CPK12 is required for plant adaptation to salt stress. Full article
(This article belongs to the Special Issue Salinity Tolerance in Plants)
Open AccessArticle Histone H3 lysine 9 acetylation is downregulated in GDM Placentas and Calcitriol supplementation enhanced this effect
Int. J. Mol. Sci. 2018, 19(12), 4061; https://doi.org/10.3390/ijms19124061 (registering DOI)
Received: 9 November 2018 / Revised: 7 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
Despite the ever-rising incidence of Gestational Diabetes Mellitus (GDM) and its implications for long-term health of mothers and offspring, the underlying molecular mechanisms remain to be elucidated. To contribute to this, the present study’s objectives are to conduct a sex-specific analysis of active
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Despite the ever-rising incidence of Gestational Diabetes Mellitus (GDM) and its implications for long-term health of mothers and offspring, the underlying molecular mechanisms remain to be elucidated. To contribute to this, the present study’s objectives are to conduct a sex-specific analysis of active histone modifications in placentas affected by GDM and to investigate the effect of calcitriol on trophoblast cell’s transcriptional status. The expression of Histone H3 lysine 9 acetylation (H3K9ac) and Histone H3 lysine 4 trimethylation (H3K4me3) was evaluated in 40 control and 40 GDM (20 male and 20 female each) placentas using immunohistochemistry and immunofluorescence. The choriocarcinoma cell line BeWo and primary human villous trophoblast cells were treated with calcitriol (48 h). Thereafter, western blots were used to quantify concentrations of H3K9ac and the transcription factor FOXO1. H3K9ac expression was downregulated in GDM placentas, while H3K4me3 expression was not significantly different. Cell culture experiments showed a slight downregulation of H3K9ac after calcitriol stimulation at the highest concentration. FOXO1 expression showed a dose-dependent increase. Our data supports previous research suggesting that epigenetic dysregulations play a key role in gestational diabetes mellitus. Insufficient transcriptional activity may be part of its pathophysiology and this cannot be rescued by calcitriol. Full article
(This article belongs to the Special Issue Epigenetics in Metabolic and Neurological Disorders)
Open AccessReview Deciphering Auxin-Ethylene Crosstalk at a Systems Level
Int. J. Mol. Sci. 2018, 19(12), 4060; https://doi.org/10.3390/ijms19124060 (registering DOI)
Received: 13 November 2018 / Revised: 10 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
The auxin and ethylene pathways cooperatively regulate a variety of developmental processes in plants. Growth responses to ethylene are largely dependent on auxin, the key regulator of plant morphogenesis. Auxin, in turn, is capable of inducing ethylene biosynthesis and signaling, making the interaction
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The auxin and ethylene pathways cooperatively regulate a variety of developmental processes in plants. Growth responses to ethylene are largely dependent on auxin, the key regulator of plant morphogenesis. Auxin, in turn, is capable of inducing ethylene biosynthesis and signaling, making the interaction of these hormones reciprocal. Recent studies discovered a number of molecular events underlying auxin-ethylene crosstalk. In this review, we summarize the results of fine-scale and large-scale experiments on the interactions between the auxin and ethylene pathways in Arabidopsis. We integrate knowledge on molecular crosstalk events, their tissue specificity, and associated phenotypic responses to decipher the crosstalk mechanisms at a systems level. We also discuss the prospects of applying systems biology approaches to study the mechanisms of crosstalk between plant hormones. Full article
(This article belongs to the Special Issue Auxins and Cytokinins in Plant Development)
Open AccessArticle Expression Characteristics and Functional Analysis of the ScWRKY3 Gene from Sugarcane
Int. J. Mol. Sci. 2018, 19(12), 4059; https://doi.org/10.3390/ijms19124059 (registering DOI)
Received: 26 October 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
PDF Full-text (1547 KB) | Supplementary Files
Abstract
The plant-specific WRKY transcriptional regulatory factors have been proven to play vital roles in plant growth, development, and responses to biotic and abiotic stresses. However, there are few studies on the WRKY gene family in sugarcane (Saccharum spp.). In the present study,
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The plant-specific WRKY transcriptional regulatory factors have been proven to play vital roles in plant growth, development, and responses to biotic and abiotic stresses. However, there are few studies on the WRKY gene family in sugarcane (Saccharum spp.). In the present study, the characterization of a new subgroup, IIc WRKY protein ScWRKY3, from a Saccharum hybrid cultivar is reported. The ScWRKY3 protein was localized in the nucleus of Nicotiana benthamiana leaves and showed no transcriptional activation activity and no toxic effects on the yeast strain Y2HGold. An interaction between ScWRKY3 and a reported sugarcane protein ScWRKY4, was confirmed in the nucleus. The ScWRKY3 gene had the highest expression level in sugarcane stem pith. The transcript of ScWRKY3 was stable in the smut-resistant Saccharum hybrid cultivar Yacheng05-179, while it was down-regulated in the smut-susceptible Saccharum hybrid cultivar ROC22 during inoculation with the smut pathogen (Sporisorium scitamineum) at 0–72 h. ScWRKY3 was remarkably up-regulated by sodium chloride (NaCl), polyethylene glycol (PEG), and plant hormone abscisic acid (ABA), but it was down-regulated by salicylic acid (SA) and methyl jasmonate (MeJA). Moreover, transient overexpression of the ScWRKY3 gene in N. benthamiana indicated a negative regulation during challenges with the fungal pathogen Fusarium solani var. coeruleum or the bacterial pathogen Ralstonia solanacearum in N. benthamiana. The findings of the present study should accelerate future research on the identification and functional characterization of the WRKY family in sugarcane. Full article
(This article belongs to the Special Issue Plant Genetics and Molecular Breeding)
Open AccessReview The Complex Interplay between Lipids, Immune System and Interleukins in Cardio-Metabolic Diseases
Int. J. Mol. Sci. 2018, 19(12), 4058; https://doi.org/10.3390/ijms19124058 (registering DOI)
Received: 30 November 2018 / Accepted: 10 December 2018 / Published: 14 December 2018
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Abstract
Lipids and inflammation regulate each other. Early studies on this topic focused on the systemic effects that the acute inflammatory response—and interleukins—had on lipid metabolism. Today, in the era of the obesity epidemic, whose primary complications are cardio-metabolic diseases, attention has moved to
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Lipids and inflammation regulate each other. Early studies on this topic focused on the systemic effects that the acute inflammatory response—and interleukins—had on lipid metabolism. Today, in the era of the obesity epidemic, whose primary complications are cardio-metabolic diseases, attention has moved to the effects that the nutritional environment and lipid derangements have on peripheral tissues, where lipotoxicity leads to organ damage through an imbalance of chronic inflammatory responses. After an overview of the effects that acute inflammation has on the systemic lipid metabolism, this review will describe the lipid-induced immune responses that take place in peripheral tissues and lead to chronic cardio-metabolic diseases. Moreover, the anti-inflammatory effects of lipid lowering drugs, as well as the possibility of using anti-inflammatory agents against cardio-metabolic diseases, will be discussed. Full article
(This article belongs to the Special Issue The Interleukins in Health and Disease)
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Open AccessArticle RrGT2, A Key Gene Associated with Anthocyanin Biosynthesis in Rosa rugosa, Was Identified Via Virus-Induced Gene Silencing and Overexpression
Int. J. Mol. Sci. 2018, 19(12), 4057; https://doi.org/10.3390/ijms19124057 (registering DOI)
Received: 21 November 2018 / Revised: 6 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
PDF Full-text (1441 KB) | Supplementary Files
Abstract
In this study, a gene with a full-length cDNA of 1422 bp encoding 473 amino acids, designated RrGT2, was isolated from R. rugosa ‘Zizhi’ and then functionally characterized. RrGT2 transcripts were detected in various tissues and were proved that their expression patterns
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In this study, a gene with a full-length cDNA of 1422 bp encoding 473 amino acids, designated RrGT2, was isolated from R. rugosa ‘Zizhi’ and then functionally characterized. RrGT2 transcripts were detected in various tissues and were proved that their expression patterns corresponded with anthocyanins accumulation. Functional verification of RrGT2 in R. rugosa was performed via VIGS. When RrGT2 was silenced, the Rosa plants displayed a pale petal color phenotype. The detection results showed that the expression of RrGT2 was significantly downregulated, which was consistent with the decrease of all anthocyanins; while the expression of six key upstream structural genes was normal. Additionally, the in vivo function of RrGT2 was investigated via its overexpression in tobacco. In transgenic tobacco plants expressing RrGT2, anthocyanin accumulation was induced in the flowers, indicating that RrGT2 could encode a functional GT protein for anthocyanin biosynthesis and could function in other species. The application of VIGS in transgenic tobacco resulted in the treated tobacco plants presenting flowers whose phenotypes were lighter in color than those of normal plants. These results also validated and affirmed previous conclusions. Therefore, we speculated that glycosylation of RrGT2 plays a crucial role in anthocyanin biosynthesis in R. rugosa. Full article
(This article belongs to the Special Issue Plant Genetics and Molecular Breeding)
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Open AccessReview Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis
Int. J. Mol. Sci. 2018, 19(12), 4056; https://doi.org/10.3390/ijms19124056 (registering DOI)
Received: 8 November 2018 / Revised: 8 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
PDF Full-text (1785 KB)
Abstract
Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling
[...] Read more.
Over the past three-decades, Janus kinase (Jak) and signal transducer and activator of transcription (STAT) signaling has emerged as a paradigm to understand the involvement of signal transduction in development and disease pathology. At the molecular level, cytokines and interleukins steer Jak/STAT signaling to transcriptional regulation of target genes, which are involved in cell differentiation, migration, and proliferation. Jak/STAT signaling is involved in various types of blood cell disorders and cancers in humans, and its activation is associated with carcinomas that are more invasive or likely to become metastatic. Despite immense information regarding Jak/STAT regulation, the signaling network has numerous missing links, which is slowing the progress towards developing drug therapies. In mammals, many components act in this cascade, with substantial cross-talk with other signaling pathways. In Drosophila, there are fewer pathway components, which has enabled significant discoveries regarding well-conserved regulatory mechanisms. Work across species illustrates the relevance of these regulators in humans. In this review, we showcase fundamental Jak/STAT regulation mechanisms in blood cells, stem cells, and cell motility. We examine the functional relevance of key conserved regulators from Drosophila to human cancer stem cells and metastasis. Finally, we spotlight less characterized regulators of Drosophila Jak/STAT signaling, which stand as promising candidates to be investigated in cancer biology. These comparisons illustrate the value of using Drosophila as a model for uncovering the roles of Jak/STAT signaling and the molecular means by which the pathway is controlled. Full article
(This article belongs to the Special Issue Drosophila Model and Human Disease)
Open AccessReview Molecular Mechanisms Underlying the Link between Diet and DNA Methylation
Int. J. Mol. Sci. 2018, 19(12), 4055; https://doi.org/10.3390/ijms19124055 (registering DOI)
Received: 5 November 2018 / Revised: 7 December 2018 / Accepted: 10 December 2018 / Published: 14 December 2018
PDF Full-text (491 KB)
Abstract
DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation—both hypomethylation and hypermethylation—has been associated with improper gene expression, leading to several disorders.
[...] Read more.
DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation—both hypomethylation and hypermethylation—has been associated with improper gene expression, leading to several disorders. Two types of risk factors can alter the epigenetic regulation of methylation pathways: genetic factors and modifiable factors. Nutrition is one of the strongest modifiable factors, which plays a direct role in DNA methylation pathways. Large numbers of studies have investigated the effects of nutrition on DNA methylation pathways, but relatively few have focused on the biochemical mechanisms. Understanding the biological mechanisms is essential for clarifying how nutrients function in epigenetics. It is believed that nutrition affects the epigenetic regulations of DNA methylation in several possible epigenetic pathways: mainly, by altering the substrates and cofactors that are necessary for proper DNA methylation; additionally, by changing the activity of enzymes regulating the one-carbon cycle; and, lastly, through there being an epigenetic role in several possible mechanisms related to DNA demethylation activity. The aim of this article is to review the potential underlying biochemical mechanisms that are related to diet modifications in DNA methylation and demethylation. Full article
Open AccessArticle Resistance to Spot Blotch in Two Mapping Populations of Common Wheat Is Controlled by Multiple QTL of Minor Effects
Int. J. Mol. Sci. 2018, 19(12), 4054; https://doi.org/10.3390/ijms19124054 (registering DOI)
Received: 8 October 2018 / Revised: 27 November 2018 / Accepted: 7 December 2018 / Published: 14 December 2018
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Abstract
Spot blotch (SB) is an important fungal disease of wheat in South Asia and South America. Host resistance is regarded as an economical and environmentally friendly approach of controlling SB, and the inheritance of resistance is mostly quantitative. In order to gain a
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Spot blotch (SB) is an important fungal disease of wheat in South Asia and South America. Host resistance is regarded as an economical and environmentally friendly approach of controlling SB, and the inheritance of resistance is mostly quantitative. In order to gain a better understanding on the SB resistance mechanism in CIMMYT germplasm, two bi-parental mapping populations were generated, both comprising 232 F2:7 progenies. Elite CIMMYT breeding lines, BARTAI and WUYA, were used as resistant parents, whereas CIANO T79 was used as susceptible parent in both populations. The two populations were evaluated for field SB resistance at CIMMYT’s Agua Fria station for three consecutive years, from the 2012–2013 to 2014–2015 cropping seasons. Phenological traits like plant height (PH) and days to heading (DH) were also determined. Genotyping was performed using the DArTSeq genotyping-by-sequencing (GBS) platform, and a few D-genome specific SNPs and those for phenological traits were integrated for analysis. The most prominent quantitative trait locus (QTL) in both populations was found on chromosome 5AL at the Vrn-A1 locus, explaining phenotypic variations of 7–27%. Minor QTL were found on chromosomes 1B, 3A, 3B, 4B, 4D, 5B and 6D in BARTAI and on chromosomes 1B, 2A, 2D and 4B in WUYA, whereas minor QTL contributed by CIANO T79 were identified on chromosome 1B, 1D, 3A, 4B and 7A. In summary, resistance to SB in the two mapping populations was controlled by multiple minor QTL, with strong influence from Vrn-A1. Full article
(This article belongs to the Section Molecular Plant Sciences)
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Open AccessReview Store-Operated Ca2+ Entry in Breast Cancer Cells: Remodeling and Functional Role
Int. J. Mol. Sci. 2018, 19(12), 4053; https://doi.org/10.3390/ijms19124053 (registering DOI)
Received: 14 November 2018 / Revised: 3 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
Breast cancer is the most common type of cancer in women. It is a heterogeneous disease that ranges from the less undifferentiated luminal A to the more aggressive basal or triple negative breast cancer molecular subtype. Ca2+ influx from the extracellular medium,
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Breast cancer is the most common type of cancer in women. It is a heterogeneous disease that ranges from the less undifferentiated luminal A to the more aggressive basal or triple negative breast cancer molecular subtype. Ca2+ influx from the extracellular medium, but more specifically store-operated Ca2+ entry (SOCE), has been reported to play an important role in tumorigenesis and the maintenance of a variety of cancer hallmarks, including cell migration, proliferation, invasion or epithelial to mesenchymal transition. Breast cancer cells remodel the expression and functional role of the molecular components of SOCE. This review focuses on the functional role and remodeling of SOCE in breast cancer cells. The current studies suggest the need to deepen our understanding of SOCE in the biology of the different breast cancer subtypes in order to develop new and specific therapeutic strategies. Full article
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Open AccessReview Perspectives of RAS and RHEB GTPase Signaling Pathways in Regenerating Brain Neurons
Int. J. Mol. Sci. 2018, 19(12), 4052; https://doi.org/10.3390/ijms19124052 (registering DOI)
Received: 14 November 2018 / Revised: 5 December 2018 / Accepted: 13 December 2018 / Published: 14 December 2018
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Abstract
Cellular activation of RAS GTPases into the GTP-binding “ON” state is a key switch for regulating brain functions. Molecular protein structural elements of rat sarcoma (RAS) and RAS homolog protein enriched in brain (RHEB) GTPases involved in this switch are discussed including their
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Cellular activation of RAS GTPases into the GTP-binding “ON” state is a key switch for regulating brain functions. Molecular protein structural elements of rat sarcoma (RAS) and RAS homolog protein enriched in brain (RHEB) GTPases involved in this switch are discussed including their subcellular membrane localization for triggering specific signaling pathways resulting in regulation of synaptic connectivity, axonal growth, differentiation, migration, cytoskeletal dynamics, neural protection, and apoptosis. A beneficial role of neuronal H-RAS activity is suggested from cellular and animal models of neurodegenerative diseases. Recent experiments on optogenetic regulation offer insights into the spatiotemporal aspects controlling RAS/mitogen activated protein kinase (MAPK) or phosphoinositide-3 kinase (PI3K) pathways. As optogenetic manipulation of cellular signaling in deep brain regions critically requires penetration of light through large distances of absorbing tissue, we discuss magnetic guidance of re-growing axons as a complementary approach. In Parkinson’s disease, dopaminergic neuronal cell bodies degenerate in the substantia nigra. Current human trials of stem cell-derived dopaminergic neurons must take into account the inability of neuronal axons navigating over a large distance from the grafted site into striatal target regions. Grafting dopaminergic precursor neurons directly into the degenerating substantia nigra is discussed as a novel concept aiming to guide axonal growth by activating GTPase signaling through protein-functionalized intracellular magnetic nanoparticles responding to external magnets. Full article
(This article belongs to the Special Issue Small GTPases)
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Open AccessArticle Supraoptimal Cytokinin Content Inhibits Rice Seminal Root Growth by Reducing Root Meristem Size and Cell Length via Increased Ethylene Content
Int. J. Mol. Sci. 2018, 19(12), 4051; https://doi.org/10.3390/ijms19124051 (registering DOI)
Received: 30 October 2018 / Revised: 30 November 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Cytokinins (CKs), a class of phytohormone, regulate root growth in a dose-dependent manner. A certain threshold content of CK is required for rapid root growth, but supraoptimal CK content inhibits root growth, and the mechanism of this inhibition remains unclear in rice. In
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Cytokinins (CKs), a class of phytohormone, regulate root growth in a dose-dependent manner. A certain threshold content of CK is required for rapid root growth, but supraoptimal CK content inhibits root growth, and the mechanism of this inhibition remains unclear in rice. In this study, treatments of lovastatin (an inhibitor of CK biosynthesis) and kinetin (KT; a synthetic CK) were found to inhibit rice seminal root growth in a dose-dependent manner, suggesting that endogenous CK content is optimal for rapid growth of the seminal root in rice. KT treatment strongly increased ethylene level by upregulating the transcription of ethylene biosynthesis genes. Ethylene produced in response to exogenous KT inhibited rice seminal root growth by reducing meristem size via upregulation of OsIAA3 transcription and reduced cell length by downregulating transcription of cell elongation-related genes. Moreover, the effects of KT treatment on rice seminal root growth, root meristem size and cell length were rescued by treatment with aminoethoxyvinylglycine (an inhibitor of ethylene biosynthesis), which restored ethylene level and transcription levels of OsIAA3 and cell elongation-related genes. Supraoptimal CK content increases ethylene level by promoting ethylene biosynthesis, which in turn inhibits rice seminal root growth by reducing root meristem size and cell length. Full article
(This article belongs to the Special Issue Auxins and Cytokinins in Plant Development)
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Open AccessArticle Fucoidan Alleviates Acetaminophen-Induced Hepatotoxicity via Oxidative Stress Inhibition and Nrf2 Translocation
Int. J. Mol. Sci. 2018, 19(12), 4050; https://doi.org/10.3390/ijms19124050 (registering DOI)
Received: 25 November 2018 / Revised: 9 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have
[...] Read more.
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have not been sufficiently addressed. In the present study, male Institute of Cancer Research (ICR) mice aged 6 weeks were subjected to a single APAP (500 mg/kg) intraperitoneal injection after 7 days of fucoidan (100 or 200 mg/kg/day) or bicyclol intragastric administration. The mice continued to be administered fucoidan or bicyclol once per day, and were sacrificed at an indicated time. The indexes evaluated included liver pathological changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in the liver, and related proteins levels (CYP2E1, pJNK and Bax). Furthermore, human hepatocyte HL-7702 cell line was used to elucidate the potential molecular mechanism of fucoidan. The mitochondrial membrane potential (MMP) and nuclear factor-erythroid 2-related factor (Nrf2) translocation in HL-7702 cells were determined. The results showed that fucoidan pretreatment reduced the levels of ALT, AST, ROS, and MDA, while it enhanced the levels of GSH, SOD, and CAT activities. Additionally, oxidative stress-induced phosphorylated c-Jun N-terminal protein kinase (JNK) and decreased MMP were attenuated by fucoidan. Although the nuclear Nrf2 was induced after APAP incubation, fucoidan further enhanced Nrf2 in cell nuclei and total expression of Nrf2. These results indicated that fucoidan ameliorated APAP hepatotoxicity, and the mechanism might be related to Nrf2-mediated oxidative stress. Full article
(This article belongs to the Special Issue Plant Natural Products for Human Health)
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Open AccessArticle Facile Preparation of Gold-Decorated Fe3O4 Nanoparticles for CT and MR Dual-Modal Imaging
Int. J. Mol. Sci. 2018, 19(12), 4049; https://doi.org/10.3390/ijms19124049 (registering DOI)
Received: 16 November 2018 / Revised: 2 December 2018 / Accepted: 4 December 2018 / Published: 14 December 2018
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Abstract
The development of a multifunctional nanoprobe capable of non-invasive multimodal imaging is crucial for precise tumour diagnosis. Herein, we report a facile polymer-assisted method to produce Au-Fe3O4 nanocomposites (NCPs) for the dual-modal magnetic resonance (MR) and X-ray computed tomography (CT)
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The development of a multifunctional nanoprobe capable of non-invasive multimodal imaging is crucial for precise tumour diagnosis. Herein, we report a facile polymer-assisted method to produce Au-Fe3O4 nanocomposites (NCPs) for the dual-modal magnetic resonance (MR) and X-ray computed tomography (CT) imaging of tumours. In this approach, amino-functionalized Au nanospheres were first obtained by surface modification of the bifunctional polymer SH-PEG-NH2. Hydrophilic and carboxyl-functionalized Fe3O4 nanoparticles were produced by phase transfer of reverse micelle oxidation in our previous work. The Au nanoparticles were conjugated with hydrophilic Fe3O4 nanoparticles through an amide reaction. The obtained Au-Fe3O4 nanocomposites display a high r2 relativity (157.92 mM−1 s−1) and a Hounsfield units (HU) value (270 HU) at Au concentration of 8 mg/mL and could be applied as nanoprobes for the dual-modal MR/CT imaging of a xenografted tumour model. Our work provides a facile method to prepare Au-Fe3O4 nanocomposites for dual-modal MR/CT imaging, and this method can be extended to prepare other multifunctional nanoparticles for multimodal bioimaging. Full article
(This article belongs to the Special Issue Translating Gold Nanoparticles to Diagnostics and Therapeutics)
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Open AccessReview Pharmacological Utilization of Bergamottin, Derived from Grapefruits, in Cancer Prevention and Therapy
Int. J. Mol. Sci. 2018, 19(12), 4048; https://doi.org/10.3390/ijms19124048 (registering DOI)
Received: 21 November 2018 / Revised: 11 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Cancer still remains one of the leading causes of death worldwide. In spite of significant advances in treatment options and the advent of novel targeted therapies, there still remains an unmet need for the identification of novel pharmacological agents for cancer therapy. This
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Cancer still remains one of the leading causes of death worldwide. In spite of significant advances in treatment options and the advent of novel targeted therapies, there still remains an unmet need for the identification of novel pharmacological agents for cancer therapy. This has led to several studies evaluating the possible application of natural agents found in vegetables, fruits, or plant-derived products that may be useful for cancer treatment. Bergamottin is a furanocoumarin derived from grapefruits and is also a well-known cytochrome P450 inhibitor. Recent studies have demonstrated potent anti-oxidative, anti-inflammatory, and anti-cancer properties of grapefruit furanocoumarin both in vitro and in vivo. The present review focuses on the potential anti-neoplastic effects of bergamottin in different tumor models and briefly describes the molecular targets affected by this agent. Full article
(This article belongs to the Special Issue Feature Annual Reviews in Molecular Sciences 2019)
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Open AccessReview Multiple Links between HD-Zip Proteins and Hormone Networks
Int. J. Mol. Sci. 2018, 19(12), 4047; https://doi.org/10.3390/ijms19124047
Received: 31 October 2018 / Revised: 6 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
HD-Zip proteins are unique to plants, and contain a homeodomain closely linked to a leucine zipper motif, which are involved in dimerization and DNA binding. Based on homology in the HD-Zip domain, gene structure and the presence of additional motifs, HD-Zips are divided
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HD-Zip proteins are unique to plants, and contain a homeodomain closely linked to a leucine zipper motif, which are involved in dimerization and DNA binding. Based on homology in the HD-Zip domain, gene structure and the presence of additional motifs, HD-Zips are divided into four families, HD-Zip I–IV. Phylogenetic analysis of HD-Zip genes using transcriptomic and genomic datasets from a wide range of plant species indicate that the HD-Zip protein class was already present in green algae. Later, HD-Zips experienced multiple duplication events that promoted neo- and sub-functionalizations. HD-Zip proteins are known to control key developmental and environmental responses, and a growing body of evidence indicates a strict link between members of the HD-Zip II and III families and the auxin machineries. Interactions of HD-Zip proteins with other hormones such as brassinolide and cytokinin have also been described. More recent data indicate that members of different HD-Zip families are directly involved in the regulation of abscisic acid (ABA) homeostasis and signaling. Considering the fundamental role of specific HD-Zip proteins in the control of key developmental pathways and in the cross-talk between auxin and cytokinin, a relevant role of these factors in adjusting plant growth and development to changing environment is emerging. Full article
(This article belongs to the Special Issue Auxins and Cytokinins in Plant Development)
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Open AccessArticle Knockout of SlSBPASE Suppresses Carbon Assimilation and Alters Nitrogen Metabolism in Tomato Plants
Int. J. Mol. Sci. 2018, 19(12), 4046; https://doi.org/10.3390/ijms19124046
Received: 23 November 2018 / Revised: 11 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
Sedoheptulose-1,7-bisphosphatase (SBPase) is an enzyme in the Calvin–Benson cycle and has been documented to be important in carbon assimilation, growth and stress tolerance in plants. However, information on the impact of SBPase on carbon assimilation and nitrogen metabolism in tomato plants (Solanum
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Sedoheptulose-1,7-bisphosphatase (SBPase) is an enzyme in the Calvin–Benson cycle and has been documented to be important in carbon assimilation, growth and stress tolerance in plants. However, information on the impact of SBPase on carbon assimilation and nitrogen metabolism in tomato plants (Solanum lycopersicum) is rather limited. In the present study, we investigated the role of SBPase in carbon assimilation and nitrogen metabolism in tomato plants by knocking out SBPase gene SlSBPASE using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology. Compared with wild-type plants, slsbpase mutant plants displayed severe growth retardation. Further analyses showed that knockout of SlSBPASE led to a substantial reduction in SBPase activity and as a consequence, ribulose-1,5-bisphosphate (RuBP) regeneration and carbon assimilation rate were dramatically inhibited in slsbpase mutant plants. It was further observed that much lower levels of sucrose and starch were accumulated in slsbpase mutant plants than their wild-type counterparts during the photoperiod. Intriguingly, mutation in SlSBPASE altered nitrogen metabolism as demonstrated by changes in levels of protein and amino acids and activities of nitrogen metabolic enzymes. Collectively, our data suggest that SlSBPASE is required for optimal growth, carbon assimilation and nitrogen metabolism in tomato plants. Full article
(This article belongs to the Section Molecular Plant Sciences)
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Open AccessReview Role of Cytokinins in Senescence, Antioxidant Defence and Photosynthesis
Int. J. Mol. Sci. 2018, 19(12), 4045; https://doi.org/10.3390/ijms19124045
Received: 24 October 2018 / Revised: 5 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Cytokinins modulate a number of important developmental processes, including the last phase of leaf development, known as senescence, which is associated with chlorophyll breakdown, photosynthetic apparatus disintegration and oxidative damage. There is ample evidence that cytokinins can slow down all these senescence-accompanying changes.
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Cytokinins modulate a number of important developmental processes, including the last phase of leaf development, known as senescence, which is associated with chlorophyll breakdown, photosynthetic apparatus disintegration and oxidative damage. There is ample evidence that cytokinins can slow down all these senescence-accompanying changes. Here, we review relationships between the various mechanisms of action of these regulatory molecules. We highlight their connection to photosynthesis, the pivotal process that generates assimilates, however may also lead to oxidative damage. Thus, we also focus on cytokinin induction of protective responses against oxidative damage. Activation of antioxidative enzymes in senescing tissues is described as well as changes in the levels of naturally occurring antioxidative compounds, such as phenolic acids and flavonoids, in plant explants. The main goal of this review is to show how the biological activities of cytokinins may be related to their chemical structure. New links between molecular aspects of natural cytokinins and their synthetic derivatives with antisenescent properties are described. Structural motifs in cytokinin molecules that may explain why these molecules play such a significant regulatory role are outlined. Full article
(This article belongs to the Special Issue Auxins and Cytokinins in Plant Development)
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Open AccessArticle Evolution from Natural β-Carboline Alkaloids to Obtain 1,2,4,9-tetrahydro-3-thia-9-aza-fluorene Derivatives as Potent Fungicidal Agents against Rhizoctonia solani
Int. J. Mol. Sci. 2018, 19(12), 4044; https://doi.org/10.3390/ijms19124044 (registering DOI)
Received: 5 November 2018 / Revised: 5 December 2018 / Accepted: 10 December 2018 / Published: 14 December 2018
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Abstract
Rice sheath blight, caused by Rhizoctonia solani, is a globally important rice disease and the increasing resistance of this pathogen highlights the need for new active compounds against rice sheath blight. In this study, natural β-carboline alkaloids were optimized to obtain
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Rice sheath blight, caused by Rhizoctonia solani, is a globally important rice disease and the increasing resistance of this pathogen highlights the need for new active compounds against rice sheath blight. In this study, natural β-carboline alkaloids were optimized to obtain a series of 1,2,4,9-tetrahydro-3-thia-9-aza-fluorene derivatives and evaluated for their fungicidal activity and mode of action against R. solani. Of these compounds, 18 exhibited significant in vitro fungicidal activity against R. solani, with an EC50 value of 2.35 μg/mL, and was more active than validamycin A. In vivo bioassay also demonstrated that 18 displayed superior protective and curative activities as compared to validamycin A. Mechanistically, 18 not only induced the loss of mitochondrial membrane potential and accumulation of reactive oxygen species, but also interfered with DNA synthesis. Therefore, compound 18 displayed pronounced in vitro and in vivo fungicidal activity against R. solani and could be used as a potential candidate for the control of rice sheath blight. Full article
(This article belongs to the Section Molecular Plant Sciences)
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Open AccessArticle Association between Plasma HMGB-1 and Silicosis: A Case-Control Study
Int. J. Mol. Sci. 2018, 19(12), 4043; https://doi.org/10.3390/ijms19124043
Received: 23 November 2018 / Accepted: 10 December 2018 / Published: 14 December 2018
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Abstract
High-mobility group box-1 (HMGB-1) has been associated with fibrotic diseases. However, the role of HMGB-1 in silicosis is still uncertain. In this study, we conducted a case-control study involving 74 patients with silicosis and 107 age/gender-matched healthy controls in China. An Enzyme-linked immunosorbent
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High-mobility group box-1 (HMGB-1) has been associated with fibrotic diseases. However, the role of HMGB-1 in silicosis is still uncertain. In this study, we conducted a case-control study involving 74 patients with silicosis and 107 age/gender-matched healthy controls in China. An Enzyme-linked immunosorbent assay (ELISA) was used to examine the concentrations of plasma HMGB-1 among all subjects. A logistic regression model and receiver operating characteristic curve (ROC) analysis were performed to assess the relationships between HMGB-1 and silicosis. We observed that plasma HMGB-1 concentrations were significantly increased in silicosis patients when compared with healthy controls (p < 0.05). Each 1 ng/mL increase in plasma HMGB-1 was positively associated with increased odds of silicosis, and the odds ratio (OR) (95% confidence interval) was 1.86 (1.52, 2.27). Additionally, compared with subjects with lower HMGB-1 concentrations, increased odds of silicosis were observed in those with higher HMGB-1 concentrations, and the OR was 15.33 (6.70, 35.10). Nonlinear models including a natural cubic spline function of continuous HMGB-1 yielded similar results. In ROC analyses, we found that plasma HMGB-1 >7.419 ng/mL had 81.6% sensitivity and 80.4% specificity for silicosis, and the area under the curve (AUC) was 0.84. Our results demonstrated that elevated plasma HMGB-1 was positivity associated with increased OR of silicosis. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessArticle Selenium-Enriched Brushite: A Novel Biomaterial for Potential Use in Bone Tissue Engineering
Int. J. Mol. Sci. 2018, 19(12), 4042; https://doi.org/10.3390/ijms19124042
Received: 18 November 2018 / Revised: 7 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
In this study, a novel biomaterial, i.e., brushite containing 0.67 wt% of selenium (Se-Bru) was synthesized via a wet precipitation method. Pure, unsubstituted brushite (Bru) was synthesized via the same method and used as a reference material. Different techniques of instrumental analysis were
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In this study, a novel biomaterial, i.e., brushite containing 0.67 wt% of selenium (Se-Bru) was synthesized via a wet precipitation method. Pure, unsubstituted brushite (Bru) was synthesized via the same method and used as a reference material. Different techniques of instrumental analysis were applied to investigate and compare physicochemical properties of both materials. Fourier-Transform Infrared Spectroscopy confirmed the chemical identity of both materials. Scanning Electron Microscopy (SEM) was used to study the morphology and indicated that both samples (Bru and Se-Bru) consisted of plate-like microcrystals. Powder X-ray Diffraction (PXRD) showed that Bru, as well as Se-Bru were crystallographically homogenous. What is more, the data obtained from PXRD studies revealed that the substitution of selenite ions into the crystal structure of the material had clearly affected its lattice parameters. The incorporation of selenium was also confirmed by solid-state 1H→31P CP MAS kinetics experiments. Additionally, studies on the release kinetics of the elements forming Se-Bru and preliminary cytotoxicity tests were conducted. This preliminary research will favor a better understanding of ionic substitution in calcium phosphates and may be a starting point for the development of selenium-doped brushite cements for potential use in bone tissue impairments treatment. Full article
(This article belongs to the Special Issue Biomaterials for Musculoskeletal System)
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Open AccessReview Rac GTPases in Hematological Malignancies
Int. J. Mol. Sci. 2018, 19(12), 4041; https://doi.org/10.3390/ijms19124041
Received: 11 November 2018 / Revised: 11 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
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Abstract
Emerging evidence suggests that crosstalk between hematologic tumor cells and the tumor microenvironment contributes to leukemia and lymphoma cell migration, survival, and proliferation. The supportive tumor cell-microenvironment interactions and the resulting cellular processes require adaptations and modulations of the cytoskeleton. The Rac subfamily
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Emerging evidence suggests that crosstalk between hematologic tumor cells and the tumor microenvironment contributes to leukemia and lymphoma cell migration, survival, and proliferation. The supportive tumor cell-microenvironment interactions and the resulting cellular processes require adaptations and modulations of the cytoskeleton. The Rac subfamily of the Rho family GTPases includes key regulators of the cytoskeleton, with essential functions in both normal and transformed leukocytes. Rac proteins function downstream of receptor tyrosine kinases, chemokine receptors, and integrins, orchestrating a multitude of signals arising from the microenvironment. As such, it is not surprising that deregulation of Rac expression and activation plays a role in the development and progression of hematological malignancies. In this review, we will give an overview of the specific contribution of the deregulation of Rac GTPases in hematologic malignancies. Full article
(This article belongs to the Special Issue Small GTPases)
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Open AccessEditorial Skin Pigmentation: Is the Control of Melanogenesis a Target within Reach?
Int. J. Mol. Sci. 2018, 19(12), 4040; https://doi.org/10.3390/ijms19124040
Received: 10 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
Skin pigmentation represents one of the most peculiar traits of human beings and its alteration as a consequence of pathological conditions has a dramatic impact on the wellness of individuals and their social relationships. [...] Full article
(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)
Open AccessArticle Evolutionary Analysis of Plastid Genomes of Seven Lonicera L. Species: Implications for Sequence Divergence and Phylogenetic Relationships
Int. J. Mol. Sci. 2018, 19(12), 4039; https://doi.org/10.3390/ijms19124039
Received: 10 November 2018 / Revised: 7 December 2018 / Accepted: 11 December 2018 / Published: 14 December 2018
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Abstract
Plant plastomes play crucial roles in species evolution and phylogenetic reconstruction studies due to being maternally inherited and due to the moderate evolutionary rate of genomes. However, patterns of sequence divergence and molecular evolution of the plastid genomes in the horticulturally- and economically-important
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Plant plastomes play crucial roles in species evolution and phylogenetic reconstruction studies due to being maternally inherited and due to the moderate evolutionary rate of genomes. However, patterns of sequence divergence and molecular evolution of the plastid genomes in the horticulturally- and economically-important Lonicera L. species are poorly understood. In this study, we collected the complete plastomes of seven Lonicera species and determined the various repeat sequence variations and protein sequence evolution by comparative genomic analysis. A total of 498 repeats were identified in plastid genomes, which included tandem (130), dispersed (277), and palindromic (91) types of repeat variations. Simple sequence repeat (SSR) elements analysis indicated the enriched SSRs in seven genomes to be mononucleotides, followed by tetra-nucleotides, dinucleotides, tri-nucleotides, hex-nucleotides, and penta-nucleotides. We identified 18 divergence hotspot regions (rps15, rps16, rps18, rpl23, psaJ, infA, ycf1, trnN-GUU-ndhF, rpoC2-rpoC1, rbcL-psaI, trnI-CAU-ycf2, psbZ-trnG-UCC, trnK-UUU-rps16, infA-rps8, rpl14-rpl16, trnV-GAC-rrn16, trnL-UAA intron, and rps12-clpP) that could be used as the potential molecular genetic markers for the further study of population genetics and phylogenetic evolution of Lonicera species. We found that a large number of repeat sequences were distributed in the divergence hotspots of plastid genomes. Interestingly, 16 genes were determined under positive selection, which included four genes for the subunits of ribosome proteins (rps7, rpl2, rpl16, and rpl22), three genes for the subunits of photosystem proteins (psaJ, psbC, and ycf4), three NADH oxidoreductase genes (ndhB, ndhH, and ndhK), two subunits of ATP genes (atpA and atpB), and four other genes (infA, rbcL, ycf1, and ycf2). Phylogenetic analysis based on the whole plastome demonstrated that the seven Lonicera species form a highly-supported monophyletic clade. The availability of these plastid genomes provides important genetic information for further species identification and biological research on Lonicera. Full article
(This article belongs to the Special Issue Chloroplast 2.0)
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Open AccessArticle Zebrafish Mutants Carrying Leptin a (lepa) Gene Deficiency Display Obesity, Anxiety, Less Aggression and Fear, and Circadian Rhythm and Color Preference Dysregulation
Int. J. Mol. Sci. 2018, 19(12), 4038; https://doi.org/10.3390/ijms19124038
Received: 9 November 2018 / Revised: 5 December 2018 / Accepted: 11 December 2018 / Published: 13 December 2018
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Abstract
Leptin, a hormone secreted by peripheral adipose tissues, regulates the appetite in animals. Recently, evidence has shown that leptin also plays roles in behavioral response in addition to controlling appetite. In this study, we examined the potential function of leptin on non-appetite behaviors
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Leptin, a hormone secreted by peripheral adipose tissues, regulates the appetite in animals. Recently, evidence has shown that leptin also plays roles in behavioral response in addition to controlling appetite. In this study, we examined the potential function of leptin on non-appetite behaviors in zebrafish model. By using genome editing tool of Transcription activator-like effector nuclease (TALEN), we successfully knocked out leptin a (lepa) gene by deleting 4 bp within coding region to create a premature-translation stop. Morphological and appetite analysis showed the lepa KO fish display a phenotype with obese, good appetite and elevation of Agouti-related peptide (AgRP) and Ghrelin hormones, consistent with the canonical function of leptin in controlling food intake. By multiple behavior endpoint analyses, including novel tank, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm, and color preference assay, we found the lepa KO fish display an anxiogenic phenotype showing hyperactivity with rapid swimming, less freezing time, less fear to predator, loose shoaling area forming, and circadian rhythm and color preference dysregulations. Using biochemical assays, melatonin, norepinephrine, acetylcholine and serotonin levels in the brain were found to be significantly reduced in lepa KO fish, while the levels of dopamine, glycine and cortisol in the brain were significantly elevated. In addition, the brain ROS level was elevated, and the anti-oxidative enzyme catalase level was reduced. Taken together, by performing loss-of-function multiple behavior endpoint testing and biochemical analysis, we provide strong evidence for a critical role of lepa gene in modulating anxiety, aggression, fear, and circadian rhythm behaviors in zebrafish for the first time. Full article
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Open AccessArticle Glucosinolate Profiling and Expression Analysis of Glucosinolate Biosynthesis Genes Differentiate White Mold Resistant and Susceptible Cabbage Lines
Int. J. Mol. Sci. 2018, 19(12), 4037; https://doi.org/10.3390/ijms19124037
Received: 24 October 2018 / Revised: 7 December 2018 / Accepted: 11 December 2018 / Published: 13 December 2018
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Abstract
Sclerotinia stem rot (white mold), caused by the fungus Sclerotinia sclerotiorum, is a serious disease of Brassica crops worldwide. Despite considerable progress in investigating plant defense mechanisms against this pathogen, which have revealed the involvement of glucosinolates, the host–pathogen interaction between cabbage
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Sclerotinia stem rot (white mold), caused by the fungus Sclerotinia sclerotiorum, is a serious disease of Brassica crops worldwide. Despite considerable progress in investigating plant defense mechanisms against this pathogen, which have revealed the involvement of glucosinolates, the host–pathogen interaction between cabbage (Brassica oleracea) and S. sclerotiorum has not been fully explored. Here, we investigated glucosinolate profiles and the expression of glucosinolate biosynthesis genes in white-mold-resistant (R) and -susceptible (S) lines of cabbage after infection with S. sclerotiorum. The simultaneous rise in the levels of the aliphatic glucosinate glucoiberverin (GIV) and the indolic glucosinate glucobrassicin (GBS) was linked to white mold resistance in cabbage. Principal component analysis showed close association between fungal treatment and cabbage GIV and GBS contents. The correlation analysis showed significant positive associations between GIV content and expression of the glucosinolate biosynthesis genes ST5b-Bol026202 and ST5c-Bol030757, and between GBS content and the expression of the glucosinolate biosynthesis genes ST5a-Bol026200 and ST5a-Bol039395. Our results revealed that S. sclerotiorum infection of cabbage induces the expression of glucosinolate biosynthesis genes, altering the content of individual glucosinolates. This relationship between the expression of glucosinolate biosynthesis genes and accumulation of the corresponding glucosinolates and resistance to white mold extends the molecular understanding of glucosinolate-negotiated defense against S. sclerotiorum in cabbage. Full article
(This article belongs to the Section Molecular Plant Sciences)
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Open AccessReview Targeting Cancer Stem Cells to Overcome Chemoresistance
Int. J. Mol. Sci. 2018, 19(12), 4036; https://doi.org/10.3390/ijms19124036
Received: 20 November 2018 / Revised: 8 December 2018 / Accepted: 10 December 2018 / Published: 13 December 2018
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Abstract
Cancers are heterogeneous at the cell level, and the mechanisms leading to cancer heterogeneity could be clonal evolution or cancer stem cells. Cancer stem cells are resistant to most anti-cancer treatments and could be preferential targets to reverse this resistance, either targeting stemness
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Cancers are heterogeneous at the cell level, and the mechanisms leading to cancer heterogeneity could be clonal evolution or cancer stem cells. Cancer stem cells are resistant to most anti-cancer treatments and could be preferential targets to reverse this resistance, either targeting stemness pathways or cancer stem cell surface markers. Gold nanoparticles have emerged as innovative tools, particularly for photo-thermal therapy since they can be excited by laser to induce hyperthermia. Gold nanoparticles can be functionalized with antibodies to specifically target cancer stem cells. Preclinical studies using photo-thermal therapy have demonstrated the feasibility of targeting chemo-resistant cancer cells to reverse clinical chemoresistance. Here, we review the data linking cancer stem cells and chemoresistance and discuss the way to target them to reverse resistance. We particularly focus on the use of functionalized gold nanoparticles in the treatment of chemo-resistant metastatic cancers. Full article
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Open AccessReview DA-9701 (Motilitone): A Multi-Targeting Botanical Drug for the Treatment of Functional Dyspepsia
Int. J. Mol. Sci. 2018, 19(12), 4035; https://doi.org/10.3390/ijms19124035
Received: 9 November 2018 / Revised: 7 December 2018 / Accepted: 7 December 2018 / Published: 13 December 2018
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Abstract
Functional dyspepsia (FD) is the most common functional gastrointestinal disorder (FGID). FD is characterized by bothersome symptoms such as postprandial fullness, early satiety, and epigastric pain or burning sensations in the upper abdomen. The complexity and heterogeneity of FD pathophysiology, which involves multiple
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Functional dyspepsia (FD) is the most common functional gastrointestinal disorder (FGID). FD is characterized by bothersome symptoms such as postprandial fullness, early satiety, and epigastric pain or burning sensations in the upper abdomen. The complexity and heterogeneity of FD pathophysiology, which involves multiple mechanisms, make both treatment and new drug development for FD difficult. Current medicines for FD targeting a single pathway have failed to show satisfactory efficacy and safety. On the other hand, multicomponent herbal medicines that act on multiple targets may be a promising alternative treatment for FD. DA-9701 (Motilitone), a botanical drug consisting of Corydalis Tuber and Pharbitidis Semen, has been prescribed for FD since it was launched in Korea in 2011. It has multiple mechanisms of action such as prokinetic effects, fundus relaxation, and visceral analgesia, which are mediated by dopamine D2 and several serotonin receptors involved in gastrointestinal (GI) functions. In clinical studies, DA-9701 has been found to be beneficial for improvement of FD symptoms and GI functions in FD patients, while showing better safety compared to that associated with conventional medicines. In this review, we provide updated information on the pharmacological effects, safety, and clinical results of DA-9701 for the treatment of FGIDs. Full article
(This article belongs to the Special Issue Health Promoting Effects of Phytochemicals)
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Open AccessReview Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy
Int. J. Mol. Sci. 2018, 19(12), 4034; https://doi.org/10.3390/ijms19124034
Received: 28 September 2018 / Revised: 7 December 2018 / Accepted: 11 December 2018 / Published: 13 December 2018
PDF Full-text (1911 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Diabetic retinopathy (DR) is the most common diabetic microvascular complication and major cause of blindness in working-age adults. According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in
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Diabetic retinopathy (DR) is the most common diabetic microvascular complication and major cause of blindness in working-age adults. According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in the disease etiology and pathogenesis, molecular understanding of end-stage PDR, characterized by ischemia- and inflammation-associated neovascularization and fibrosis, remains incomplete due to the limited availability of ideal clinical samples and experimental research models. Since a great portion of patients do not benefit from current treatments, improved therapies are essential. DR is known to be a complex and multifactorial disease featuring the interplay of microvascular, neurodegenerative, metabolic, genetic/epigenetic, immunological, and inflammation-related factors. Particularly, deeper knowledge on the mechanisms and pathophysiology of most advanced PDR is critical. Lymphatic-like vessel formation coupled with abnormal endothelial differentiation and progenitor cell involvement in the neovascularization associated with PDR are novel recent findings which hold potential for improved DR treatment. Understanding the underlying mechanisms of PDR pathogenesis is therefore crucial. To this goal, multidisciplinary approaches and new ex vivo models have been developed for a more comprehensive molecular, cellular and tissue-level understanding of the disease. This is the first step to gain the needed information on how PDR can be better evaluated, stratified, and treated. Full article
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Open AccessArticle Influence of Implant Material and Surface on Differentiation and Proliferation of Human Adipose-Derived Stromal Cells
Int. J. Mol. Sci. 2018, 19(12), 4033; https://doi.org/10.3390/ijms19124033
Received: 20 November 2018 / Revised: 5 December 2018 / Accepted: 12 December 2018 / Published: 13 December 2018
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Abstract
For the guided regeneration of periimplant hard and soft tissues, human adipose-derived stromal cells (hADSC) seem to be a promising source for mesenchymal stromal cells. For this, the proliferation and differentiation of hADSC were evaluated on titanium and zirconia dental implants with different
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For the guided regeneration of periimplant hard and soft tissues, human adipose-derived stromal cells (hADSC) seem to be a promising source for mesenchymal stromal cells. For this, the proliferation and differentiation of hADSC were evaluated on titanium and zirconia dental implants with different surface treatments. Results were compared to edaphic cells as human osteoblasts (hOB) and human gingival fibroblasts (HGF). Primary cells were cultured on (1) titanium implants with a polished surface (Ti-PT), (2) sandblasted and acid-etched titanium (Ti-SLA), (3) sandblasted and alkaline etched zirconia (ZrO2-ZLA) and (4) machined zirconia (ZrO2-M). The cell proliferation and differentiation on osteogenic lineage were assessed after 1, 7 and 14 days. Statistical analysis was performed by one-way ANOVA and a modified Levene test with a statistical significance at p = 0.05. PostHoc tests were performed by Bonferroni-Holm. Zirconia dental implants with rough surface (ZrO2-ZLA) showed the highest proliferation rates (p = 0.048). The osteogenic differentiation occurred early for zirconia and later for titanium implants, and it was enhanced for rough surfaces in comparison to polished/machined surfaces. Zirconia was more effective to promote the proliferation and differentiation of hADSCs in comparison to titanium. Rough surfaces were able to improve the biological response for both zirconia and titanium. Full article
(This article belongs to the Special Issue Molecular Research on Dental Materials and Biomaterials 2018)
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