المؤلفون: Cong Zhao, Jing Zhao, Pengling Ge, Yi Zheng, Kai Li, Xinyu Wu, Yuchi Zhang

المصدر: Medicinal Chemistry. 16:635-642

مصطلحات موضوعية: Candidate gene, Gene regulatory network, Computational biology, Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Drug Discovery, medicine, Animals, Gene Regulatory Networks, Gene, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, 0303 health sciences, Leptin receptor, Gene Expression Profiling, medicine.disease, Fold change, Gene expression profiling, 030220 oncology & carcinogenesis, Receptors, Leptin, Insulin Resistance, DNA microarray, Biomarkers

الوصف: Background: Molecular characterization of insulin resistance, a growing health issue worldwide, will help to develop novel strategies and accurate biomarkers for disease diagnosis and treatment. Objective: Integrative analysis of gene expression profiling and gene regulatory network was exploited to identify potential biomarkers early in the development of insulin resistance. Methods: RNA was isolated from livers of animals at three weeks of age, and whole-genome expression profiling was performed and analyzed with Agilent mouse 4×44K microarrays. Differentially expressed genes were subsequently validated by qRT-PCR. Functional characterizations of genes and their interactions were performed by Gene Ontology (GO) analysis and gene regulatory network (GRN) analysis. Results: A total of 197 genes were found to be differentially expressed by fold change ≥2 and P < 0.05 in BKS-db +/+ mice relative to sex and age-matched controls. Functional analysis suggested that these differentially expressed genes were enriched in the regulation of phosphorylation and generation of precursor metabolites which are closely associated with insulin resistance. Then a gene regulatory network associated with insulin resistance (IRGRN) was constructed by integration of these differentially expressed genes and known human protein-protein interaction network. The principal component analysis demonstrated that 67 genes in IRGRN could clearly distinguish insulin resistance from the non-disease state. Some of these candidate genes were further experimentally validated by qRT-PCR, highlighting the predictive role as biomarkers in insulin resistance. Conclusions: Our study provides new insight into the pathogenesis and treatment of insulin resistance and also reveals potential novel molecular targets and diagnostic biomarkers for insulin resistance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46be9d898dcf7047607629d7ee077852Test
https://doi.org/10.2174/1573406415666191004135450Test

المؤلفون: Haixue Kuang, Ji Li, Nannan Xing, Pengling Ge, Dongwei Han, Lei Zhu

المصدر: BioMed Research International, Vol 2015 (2015)
BioMed Research International

مصطلحات موضوعية: medicine.medical_specialty, Vinyl Compounds, Article Subject, endocrine system diseases, media_common.quotation_subject, Panax, lcsh:Medicine, Ovary, 12E7 Antigen, Primary Ovarian Insufficiency, Dinoprostone, General Biochemistry, Genetics and Molecular Biology, Follicle-stimulating hormone, Western blot, Antigens, CD, Internal medicine, Cyclohexenes, medicine, Animals, Humans, Ovulation, American ginseng, media_common, General Immunology and Microbiology, medicine.diagnostic_test, biology, Plant Extracts, lcsh:R, General Medicine, Luteinizing Hormone, medicine.disease, biology.organism_classification, female genital diseases and pregnancy complications, Rats, Premature ovarian failure, medicine.anatomical_structure, Endocrinology, Gene Expression Regulation, Female, Follicle Stimulating Hormone, Human, Luteinizing hormone, Cell Adhesion Molecules, Research Article, Hormone

الوصف: Premature ovarian failure (POF) is defined as lost ovarian functions before the age of 40. Three possible molecular markers (PLA2G4A,miR-29a, andmiR-144) have been identified in our previous study by integrated analysis of mRNA and miRNA expression profiles. The present study aimed to evaluate American ginseng root’s protective potential against POF by studying transcriptional and protein variations between American ginseng treatments and controls in rats. 4-Vinylcyclohexene diepoxide (VCD) was administered to rats for 14 days to induce POF. Additionally, American ginseng was administered to POF rats for one month, andPLA2G4A,miR-29a, andmiR-144expressions were measured in rat ovaries by qRT-PCR. PLA2G4A protein expression was examined by Western Blot, and PGE2, LH, FSH, and E2 serum levels were detected by ELISA.PLA2G4AmRNA and protein were downregulated in American ginseng-treated rats,miR-29aandmiR-144levels increased, and PGE2serum levels decreased, while LH, FSH, and E2 increased compared to POF induction alone. Analysis of transcriptional and protein variations suggested that American ginseng protects the ovary against POF by regulating prostaglandin biosynthesis, ovulation, and preventing ovarian aging. High hormone levels (PGE2, FSH, and LH) were reduced, and E2 secretion approached normal levels, leading to improved POF symptoms and abnormal ovulation.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aff4adfb6eb81bd8a4f9655655b0d263Test
https://doi.org/10.1155/2015/767124Test

المؤلفون: Pengling Ge, Nannan Xing, Ji Li, Yanhai Ren, Dongwei Han, Haixue Kuang, Lei Zhu

المصدر: Drug Development Research. 75:521-528

مصطلحات موضوعية: medicine.medical_specialty, endocrine system diseases, biology, business.industry, H&E stain, CCL2, biology.organism_classification, medicine.disease, Endometrium, PLA2G4A, female genital diseases and pregnancy complications, Premature ovarian failure, Ginseng, Endocrinology, medicine.anatomical_structure, Internal medicine, Drug Discovery, medicine, biology.protein, business, American ginseng, Hormone

الوصف: Preclinical Research Premature ovarian failure (POF) is defined by the WHO as the loss of physiological ovarian function before the age of 40. The effect of American ginseng and its underlying mechanisms in preventing and treating premature ovarian failure (POF) was studied in female Sprague-Dawley rats where POF was induced by ip administration of 4-vinylcyclohexene diepoxide (VCD). Rat behavior, serum hormone levels, ovarian and uterine size, pathological features, and ovarian tissue expression of genes associated with POF were assessed in controls, untreated POF model rats, and POF model rats treated with low- (1.125 g/kg), medium- (2.25 g/kg), and high-dose (4.5 g/kg) American ginseng. Compared with untreated POF model rats, those treated with medium- and high-dose American ginseng had more stable behavior and better coat appearance as well as serum hormone levels closer to those in control rats. Moreover, treatment with medium- or high-dose American ginseng increased ovarian and uterine size. Hematoxylin and eosin-staining revealed mature follicles and endometrium with an alternating concave/convex surface structure with visible capillaries and glands in ginseng- treated POF rats. PLA2G4A expression was positively correlated with POF, while the expression levels of PAPPA, STC2, CCL2, and NELL1 were negatively correlated with POF. Our study showed that American ginseng may effectively prevent POF and alleviate POF symptoms by regulating serum hormone levels and altering the expression levels of genes related to POF in ovarian tissue.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::35f278b3c5ee5c347710bbbc28f3db3bTest
https://doi.org/10.1002/ddr.21234Test

المؤلفون: Pengling Ge, Dongwei Han, Yuchi Zhang, Qijing Huang, Pengyang Yu

المصدر: Experimental and therapeutic medicine. 13(3)

مصطلحات موضوعية: 0301 basic medicine, Genetics, Cancer Research, Messenger RNA, Microarray, General Medicine, Articles, Biology, medicine.disease, Molecular medicine, Molecular biology, law.invention, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), Downregulation and upregulation, law, 030220 oncology & carcinogenesis, Diabetes mellitus, Gene expression, medicine, Gene, Polymerase chain reaction

الوصف: Diabetes mellitus is one of the primary diseases that pose a threat to human health. The focus of the present study is type II diabetes (T2D), which is caused by obesity and is the most prevalent type of diabetes. However, genome-scale transcriptional analysis of diabetic liver in the development process of T2D is yet to be further elucidated. Microassays were performed on liver tissue samples from three-, six- and nine-week-old db/db mice with diabetes and db/m mice to investigate differentially expressed mRNA. Based on the results of genome-scale transcriptional analysis, five genes were screened in the present study: chromobox 8 (CBX8), de-etiolated homolog 1 and damage specific DNA binding protein 1 associated 1 (DDA1), Phosphoinositide-3-kinase regulatory subunit 6 (PIK3R6), WD repeat domain 41 (WDR41) and Glycine Amidinotransferase (GATM). At three weeks of age, no significant differences in levels or ratios of expression were observed. However, at six and nine weeks, expression of CBX8, DDA1, PIK3R6 and WDR41 was significantly upregulated (P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::688c05ccd07b42d1d3eda9569cdae0e8Test
https://pubmed.ncbi.nlm.nih.gov/28450939Test

المؤلفون: Haixue Kuang, Jiaming Xie, Yuan Jiang, Jing Zhao, Pengling Ge, Yuna Kan

المصدر: Molecular medicine reports. 12(2)

مصطلحات موضوعية: Male, Cancer Research, medicine.medical_specialty, Biology, Diet, High-Fat, Biochemistry, Pathogenesis, Phosphatidylinositol 3-Kinases, Insulin resistance, Western blot, Diabetes mellitus, Internal medicine, Genetics, medicine, Hyperinsulinemia, Animals, Insulin, RNA, Messenger, Rats, Wistar, Receptor, Muscle, Skeletal, Molecular Biology, PI3K/AKT/mTOR pathway, medicine.diagnostic_test, Body Weight, medicine.disease, Rats, Endocrinology, Oncology, Gene Expression Regulation, Liver, Molecular Medicine, Calcium-sensing receptor, Insulin Resistance, Proto-Oncogene Proteins c-akt, Receptors, Calcium-Sensing, Signal Transduction

الوصف: A high-fat diet not only leads to obesity, but also leads to a predisposition towards insulin resistance (IR), which is characterized by hyperinsulinemia and reduced glucose tolerance. However, the etiology of IR remains to be fully elucidated. The present study investigated whether calcium-sensing receptor (CaSR) is involved in the development of IR in rats fed a high-fat diet. IR was induced in the rats by feeding with a fat emulsion via gavage for 2, 4, 6 or 8 weeks. Reverse transcription-quantitative polymerase chain reaction (RT-q-PCR) and western blot analysis were performed to investigate whether CaSR-associated proteins were affected. The gavage of fat emulsion for 8 weeks induced a notable decline in the insulin sensitivity index (ISI) between -4.98 and -5.60. With 6 weeks of gavage, a significant difference in the ISI was observed between the IR and control groups. The results of the RT-qPCR and western blot analysis demonstrated that phosphatidylinositol 3-kinase/Akt pathway, which is a pathway closely associated with the CaSR signaling pathway, was significantly inhibited in the rats with IR. The results of the present study provided evidence that CaSR is associated with the development of IR in rats fed a high-fat diet and suggested that CaSR may be important in the pathogenesis of diabetes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e434576a6ffb5d3eabfbdf5342a475ceTest
https://pubmed.ncbi.nlm.nih.gov/25892159Test

المؤلفون: Jiaming Xie, Ji Li, Pengling Ge, Dongwei Han, Shengjun Fan, Haixue Kuang

المصدر: Experimental and molecular pathology. 97(3)

مصطلحات موضوعية: endocrine system diseases, Clinical Biochemistry, Enzyme-Linked Immunosorbent Assay, Biology, Primary Ovarian Insufficiency, Pathology and Forensic Medicine, Rats, Sprague-Dawley, Complementary DNA, Gene expression, medicine, Animals, Cluster Analysis, Gene Regulatory Networks, RNA, Messenger, Molecular Biology, Transcription factor, Gene, Oligonucleotide Array Sequence Analysis, Genetics, Messenger RNA, Principal Component Analysis, Gene Expression Profiling, Computational Biology, medicine.disease, female genital diseases and pregnancy complications, Premature ovarian failure, Rats, Gene expression profiling, Disease Models, Animal, Female, Signal transduction

الوصف: Premature ovarian failure (POF) remains one of the major gynecological problems worldwide which affected 1% of women. Even though tremendous achievements had been acquired as opposed to years past, molecular pathogenesis associated with POF is still unclear and needs to be well-defined. The aim of this study was to analyze the gene expression profiles in the POF rat model. To predict potential regulating factors, we firstly treated female Sprague Dawley (SD) rat with 4-vinylcyclohexene diepoxide (VCD). Total RNA from ovarian tissue was converted to cDNA and hybridized to mRNA Chip array. The differentially expressed genes (DEGs) were identified by two-sample t test and assessed using hierarchical clustering and Principal Component Analysis methods. Potential regulatory targets associated with these DEGs were constructed using BisoGenet in Cytoscape. Gene Ontology (GO) and functional enrichment analysis were performed using BiNGO and DAVID, respectively. As the results, 25 DEGs were found to be closely associated with POF initiation. Hierarchical clustering and Principal Component Analysis on the transcriptional profiles revealed an excellent separation of the vehicle and POF compartments. Pathway enrichment analysis based on the disease-gene interaction network analysis led to the identification of two core signaling pathways that were strongly affected during POF initiation and progression: immune response and cardiovascular disorders. In conclusion, we constructed a gene regulatory network associated with POF using the microarray gene expression profiling, and screened out some genes or transcription factors that may be used as potential molecular therapeutic targets for POF.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee4e7e6e84aa552ddf9841447d66c95aTest
https://pubmed.ncbi.nlm.nih.gov/25445499Test

المؤلفون: Haixue Kuang, Pengling Ge, Ji Li, Jiaming Xie, Dongwei Han, Yongxin Yan

المصدر: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 30(1)

مصطلحات موضوعية: endocrine system diseases, Endocrinology, Diabetes and Metabolism, CCL2, Primary Ovarian Insufficiency, Bioinformatics, Rats, Sprague-Dawley, Endocrinology, microRNA, medicine, Animals, Humans, Gene Regulatory Networks, biology, Microarray analysis techniques, Gene Expression Profiling, Obstetrics and Gynecology, medicine.disease, Microarray Analysis, PLA2G4A, female genital diseases and pregnancy complications, Premature ovarian failure, Rats, Gene expression profiling, Disease Models, Animal, MicroRNAs, Cancer research, biology.protein, Female, DNA microarray, Hormone

الوصف: Premature ovarian failure (POF) contributes to amenorrhoea, infertility, early onset of menostasia and osteoporosis. This study profiled differentially expressed miRNAs for association with POF development. Ovarian tissue samples from 4-vinylcyclohexene diepoxide (VCD)-induced rat POF and normal rats were profiled for differentially expressed miRNAs using miRNA microarrays. A total of 63 miRNAs were up-regulated and 20 miRNAs were down-regulated in rat POF tissues versus the control tissues. qRT-PCR verified some of these altered miRNAs, i.e. miR-29a and miR-144 were down-regulated in POF tissues, which may target expression of PLA2G4A that is involved in prostaglandin biosynthesis, whereas miR-27b and miR-190 were up-regulated in POF tissues by negative control of PAPPA and CCL2 expression, respectively, both of which have been shown to relate to response to hormone stimulus. Moreover, the up-regulated miR-151 and miR-672 can also target expression of TNFSF10 and FNDC1, which have been shown to positively regulate cell apoptosis. Profiling of differentially expressed miRNAs in POF provided a novel insight into the molecular events involving the role of miRNAs in POF development with specific emphasis upon miR-27b, miR-190, miR-151, miR-672, miR-29a and miR-144.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44ef5eba10a988bf3bea1a700102d234Test
https://pubmed.ncbi.nlm.nih.gov/24188450Test