المؤلفون: Pengling Ge, Junzhi Wang, Jiaxin Li, Siqi Chen, Bo Wang, Jiaming Xie, Xinyu Wu, Xinying Hu, Jing Liu, Yi Zhang

المصدر: Letters in Drug Design & Discovery. 20

مصطلحات موضوعية: Drug Discovery, Pharmaceutical Science, Molecular Medicine

الوصف: Background: Ginseng is one of the top-selling natural products worldwide and has been shown to have significant effects. Nonetheless, there is limited research on American ginseng when compared to Asian ginseng. A small number of studies have demonstrated the therapeutic benefits of American ginseng, which include antioxidant, anti-inflammatory, and immune-stimulating activities. Objective: The objective of our research is to predict the molecular mechanism by which American ginseng combats Type 2 diabetes mellitus (T2DM) using Network Pharmacology and Molecular Docking techniques. By doing so, we aim to reveal one of the comprehensive mechanisms through which American ginseng exerts its therapeutic effects. Methods: We conducted a search for related compounds in American ginseng using the TCMSP database, which we then utilized to classify potential targets for the major ingredients. We obtained targets associated with Type 2 diabetes mellitus (T2DM) from various databases, including PharmGKB, OMIM, TTD, GeneCards, and DrugBank. Using STRING and Cytoscape software, we constructed PPI networks. We subsequently performed GO and KEGG analysis on the targets using the R programming language. Ligand and target structures were acquired from PubChem and PDB databases, respectively. Chem3D and AutoDock software was used to process the structures, while PyMoL was employed for molecular docking analysis. Results: Several investigations have indicated that PTGS2, NFKBIA, PRKCA, IL1B, NCOA2, and LPL targets are significantly associated with American ginseng's effectiveness in treating T2DM. Molecular docking analysis further validated these findings. We discovered three active components with high-affinity, namely papaverine, ginsenoside-rh2, and beta-sitosterol. Conclusion: The outcomes of our predictions could contribute to the development of American ginseng or its active constituents as an alternative therapy for T2DM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b322f373c1e6e205c6886fd863c06551Test
https://doi.org/10.2174/1570180820666230518095837Test

المؤلفون: Yuchi, Zhang, Dongwei, Han, Xiaoyan, Yu, Xinyu, Shao, Chuju, Zong, Manyu, Zhang, Junzhi, Wang, Jingwen, Liang, Pengling, Ge

المصدر: Frontiers in Genetics. 13

مصطلحات موضوعية: Genetics, Molecular Medicine, Genetics (clinical)

الوصف: We previously screened 6 differentially expressed miRNAs in ovarian tissues of 4-vinylcyclohexene diepoxide (VCD)-treated premature ovarian failure (POF) model in SD rats, including miRNA-190a-5p, miRNA-98-5p, miRNA-29a-3p, miRNA-144-5p, miRNA-27b-3p, miRNA-151-5p. In this study, to investigate the mechanisms causing the onset of POF, we first identified miRNAs with earlier differential expression at consecutive time points in the VCD-treated rat POF model and explored the mechanisms by which the target miRNAs promote POF. The SD rats were injected with VCD for 15 days to induce POF. Additionally, we collected rat blood and ovaries at the same time every day for 15 consecutive days, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), Anti-Mullerian hormone (AMH), and estradiol (E2) serum levels were detected by ELISA. Six miRNAs expression were measured in rat ovaries by qRT-PCR. Dual-luciferase reporter gene assays were employed to predict and verify the target gene (PHLPP1) of target miRNAs (miRNA-190a-5p). Western blot was examined to detect the expression levels of PHLPP1, AKT, p-AKT, FOXO3a, p-FOXO3a, and LHR proteins on the target gene PHLPP1 and its participation in the primordial follicular hyperactivation-related pathways (AKT-FOXO3a and AKT-LH/LHR). During the VCD modeling POF rat ovaries, miRNA-190a-5p was the first to show significant differential expression, i.e., 6th of VCD treating, and PHLPP1 was verified to be a direct downstream target of it. Starting from the 6th of VCD treatment, the more significant the up-regulation trend of miRNA-190a-5p expression, the more obvious the down-regulation trend of PHLPP1 and LHR mRNA and protein expression, accompanied by the more severe phosphorylation of AKT and FOXO3a proteins, thus continuously over-activating the rat primordial follicle to promote the development of POF. In conclusion, miRNA-190a-5p may become a potential biomarker for early screening of POF, and it can continuously activate primordial follicles in rats by targeting the expression of PHLPP1 and key proteins in the AKT-FOXO3a and AKT-LH/LHR pathways.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7d5541b5b32cc56a4ca28605a41d60dTest
https://doi.org/10.3389/fgene.2022.1034832Test

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