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Total 133 results found since Jan 2013.

Suppression of Antiapoptotic Bcl-2 Expression in Human Bladder Tumor Cells Exposed to Hypoxic Environment is Regulated by Caveolin-1-dependent AMPK Activity
CONCLUSIONS: We suggest a new finding for the first time that AMPK activation can regulate Hif-1α induction as well as Hif-1α-induced Cav-1 expression, and the inhibitory effect of anti-apoptotic pathway on the exposure of RT4 cells to hypoxic environment is due to Cav-1-dependent AMPK activity.PMID:33752282 | DOI:10.5213/inj.2040444.222
Source: International Neurourology Journal - March 23, 2021 Category: Urology & Nephrology Authors: Tae Jin Cho Da-Hyun Lee Bo-Hwa Choi Helen K Shinn Chang-Shin Park Source Type: research

Cancers, Vol. 13, Pages 739: Metformin Reduces Histone H3K4me3 at the Promoter Regions of Positive Cell Cycle Regulatory Genes in Lung Cancer Cells
This study aimed at understanding the effect of metformin on histone H3 methylation, DNA methylation, and chromatin accessibility in lung cancer cells. Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8. Eighty-eight genes involved in cell cycle showed reduced H3K4me3 levels in response to metformin, and 27% of them showed mRNA downregulation. Metformin suppressed the expression of H3K4 methyltransferases MLL1, MLL2, and WDR82. The siRNA-mediated knockdown of MLL2 significantly downregulated global H3K4me3 level and inhibited lung cance...
Source: Cancers - February 10, 2021 Category: Cancer & Oncology Authors: Dongho Kim Yujin Kim Bo Bin Lee Eun Yoon Cho Joungho Han Young Mog Shim Duk-Hwan Kim Tags: Article Source Type: research

AMPK inhibits Smad3-mediated autoinduction of TGF- β1 in gastric cancer cells.
AMPK inhibits Smad3-mediated autoinduction of TGF-β1 in gastric cancer cells. J Cell Mol Med. 2021 Feb 03;: Authors: Zou J, Li C, Jiang S, Luo L, Yan X, Huang D, Luo Z Abstract We have previously shown that adenine monophosphate-activated protein kinase (AMPK) regulates transforming growth factor β (TGF-β)-triggered Smad3 phosphorylation. Here we report that AMPK inhibits TGF-β1 production. First, metformin reduced mRNA levels of TGF-β1 in gastric cancer cells, in parallel to the decrease of its protein abundance. The effects were more prominent in the cells containing LKB1, an upstream kinase of...
Source: J Cell Mol Med - February 3, 2021 Category: Molecular Biology Authors: Zou J, Li C, Jiang S, Luo L, Yan X, Huang D, Luo Z Tags: J Cell Mol Med Source Type: research

Metformin-conjugated micellar system with intratumoral pH responsive de-shielding for co-delivery of doxorubicin and nucleic acid.
Abstract A novel PMet-P(cdmPEG2K) polymeric micellar carrier was developed for tumor-targeted co-delivery of DOX and nucleic acids (NA), based on polymetformin and a structure designed to lose the PEG shell in response to the acidic extracellular tumor environment. NA/DOX co-loaded micelleplexes exhibited enhanced inhibition of cell proliferation compared to DOX-loaded micelles, and displayed a higher level of cytotoxicity at an acidic pH (6.8) which mimicks the tumor microenvironment. The PMet-P(cdmPEG2K) micelles achieved significantly improved transfection with either a reporter plasmid or Cy3-siRNA, and enhanc...
Source: Biochemical Pharmacology - February 2, 2021 Category: Drugs & Pharmacology Authors: Liu Y, Sun J, Huang Y, Chen Y, Li J, Liang L, Xu J, Wan Z, Zhang B, Li Z, Li S Tags: Biochem Pharmacol Source Type: research

Coordinated regulation of miR-27 by insulin/CREB/Hippo contributes to insulin resistance.
In this study, we attempted to identify the mechanism by which miR-27 was regulated in the context of insulin resistance, a predisposed metabolic disorder in NAFLD. With cell culture experiments and animal studies, our results showed that miR-27 was coordinately regulated by insulin, CREB, and Hippo signalings. First, miR-27 was upregulated in palmitate-treated cells and high fat diet-fed mouse livers, both of which exhibited insulin resistance and increased CREB expression. Second, miR-27 was peaked in mouse liver at post-absorptive phase when CREB activity was increased. Also, miR-27 was increased rapidly in insulin-trea...
Source: Cellular Signalling - January 27, 2021 Category: Cytology Authors: Chen YJ, Chueh LY, Lee SY, Ma PF, Chen PC, Hsu SH Tags: Cell Signal Source Type: research

Metformin alleviates hydrogen peroxide-induced inflammation and oxidative stress via inhibiting P2X7R signaling in spinal cord tissue cells neurons.
In conclusion, our results show that metformin can alleviate H2O2-induced inflammation and oxidative stress via modulating the P2X7R signaling pathway. PMID: 33201730 [PubMed - as supplied by publisher]
Source: Canadian Journal of Physiology and Pharmacology - November 17, 2020 Category: Drugs & Pharmacology Authors: Wang G, Chen S, Shao Z, Li Y, Wang W, Mao L, Li J, Mei X Tags: Can J Physiol Pharmacol Source Type: research

Sirtuin-1 Inhibits Endothelin-2 Expression in Human Granulosa-Lutein Cells via HIF1A and Epigenetic Modifications †.
Sirtuin-1 Inhibits Endothelin-2 Expression in Human Granulosa-Lutein Cells via HIF1A and Epigenetic Modifications†. Biol Reprod. 2020 Oct 28;: Authors: Szymanska M, Manthe S, Shrestha K, Girsh E, Harlev A, Kisliouk T, Meidan R Abstract Endothelin-2 (EDN2) expression in granulosa cells was previously shown to be highly dependent on the hypoxic mediator, HIF1A. Here we investigated whether sirtuin-1 (SIRT1), by deacetylating HIF1A and class III histones, modulates EDN2 in human granulosa-lutein cells (hGLCs). We found that HIF1A was markedly suppressed in the presence of resveratrol or a specific SIRT...
Source: Biology of Reproduction - October 28, 2020 Category: Reproduction Medicine Authors: Szymanska M, Manthe S, Shrestha K, Girsh E, Harlev A, Kisliouk T, Meidan R Tags: Biol Reprod Source Type: research

Metformin Mitigates Cartilage Degradation by Activating AMPK/SIRT1-Mediated Autophagy in a Mouse Osteoarthritis Model
Chondrocyte dysfunction is a key mechanism underlying osteoarthritis. Metformin has shown protective effects in many diseases. The present study aimed to investigate the effects of metformin on autophagy and apoptosis in the process of osteoarthritis. A mouse osteoarthritis model was set up by surgically destabilizing medial meniscus in the knee. Intraarticular injection of metformin or vehicle was applied in the right knee for eight weeks. Mouse articular chondrocytes were isolated and passaged for in vitro experiments. Small interfering RNA (siRNA) transfection was used to silence target genes. Western blotting, immunohi...
Source: Frontiers in Pharmacology - July 23, 2020 Category: Drugs & Pharmacology Source Type: research

Identification and validation of metformin protects against PM2.5-induced macrophages cytotoxicity by targeting toll like receptor pathway.
Abstract Fine particle matter (PM2.5) has been extensively reported to contribute to the pathogenesis of pulmonary diseases. Recently, metformin has been reported to attenuate PM2.5 associated respiratory and cardiovascular injury, but the underling mechanism has not been discovered. Here, we performed comprehensively bioinformatics analysis and fully validation experiment to investigate the protection role of metformin and underling mechanism with RNAseq profile in GEO database. A combination of various bioinformatics tools including edgeR, principal component analysis (PCA), K-Means clustering, Gene Set Enrichme...
Source: Chemosphere - May 25, 2020 Category: Chemistry Authors: Shi Y, Batibawa JW, Maiga M, Sun B, Li Y, Duan J, Sun Z Tags: Chemosphere Source Type: research

Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation.
Abstract Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and impr...
Source: Cell Metabolism - May 4, 2020 Category: Cytology Authors: Bharath LP, Agrawal M, McCambridge G, Nicholas DA, Hasturk H, Liu J, Jiang K, Liu R, Guo Z, Deeney J, Apovian CM, Snyder-Cappione J, Hawk GS, Fleeman RM, Pihl RMF, Thompson K, Belkina AC, Cui L, Proctor EA, Kern PA, Nikolajczyk BS Tags: Cell Metab Source Type: research