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Hyperglycaemia aggravates periodontal inflamm-aging by promoting SETDB1-mediated LINE-1 de-repression in macrophages
CONCLUSIONS: The findings of this study show that SETDB1 regulates senescence-like phenotypical switching of macrophages and is a potential candidate for the treatment of diabetes-induced periodontal inflamm-aging.PMID:37661095 | DOI:10.1111/jcpe.13871
Source: Journal of Clinical Periodontology - September 3, 2023 Category: Dentistry Authors: Ziqi Yue Luningxiao Nie Ning Ji Yuezhang Sun Kangjian Zhu Haonan Zou Xiuxiu Song Jiao Chen Qi Wang Source Type: research

Metformin protects against retinal ischemia/reperfusion injury through AMPK-mediated mitochondrial fusion
This study aims to evaluate the protective effect of metformin against retinal I/R injury and its underlying mechanism. I/R induced reduction in retina thickness and cell number in ganglion cell layer, and metformin alleviated I/R-induced retinal injury. Both retinal I/R and simulated ischemia/reperfusion (SIR) in R28 cells down-regulated expression of mitochondrial fusion protein Mfn2 and OPA1, which led to mitochondrial fission. Metformin also alleviated damage in R28 cells, and reversed the alteration in Mfn2 and OPA1, mitochondrial fission and mitochondrial membrane potential (MMP) disruption-induced by I/R or SIR as w...
Source: Free Radical Biology and Medicine - May 30, 2023 Category: Biology Authors: Kun Zhang Tao Wang Gui-Feng Sun Jin-Xing Xiao Li-Ping Jiang Fang-Fang Tou Xin-Hui Qu Xiao-Jian Han Source Type: research

Effects of metformin on Sonic hedgehog subgroup medulloblastoma progression: In vitro and in vivo studies
Metformin is a first-line drug for type 2 diabetes, and its anticancer effects have also been widely studied in recent years. The Sonic hedgehog (Shh) signaling pathway is involved in the initiation and progression of medulloblastoma. In order to develop a new treatment strategy for medulloblastoma (MB), this study investigated the inhibitory effect of metformin on MB and the underlying mechanism of metformin on the Shh signaling pathway. The effect of metformin on proliferation was evaluated by the cell counting kit-8 (CCK-8) test and colony formation experiment. The effect of metformin on metastasis was assessed by the s...
Source: Frontiers in Pharmacology - October 7, 2022 Category: Drugs & Pharmacology Source Type: research

Metformin Improves the Senescence of Renal Tubular Epithelial Cells in a High-Glucose State Through E2F1
In this study, we explored whether metformin improves a high-glucose-induced senescence and fibrosis of renal tubular epithelial cells through cell cycle-related protein E2F1. In the in vivo experiments, the recombinant adeno-associated virus (AAV-shE2F1) knockdown E2F1 gene was injected into the tail vein of 16-weeks-old db/db mice for 8 weeks. The 16-week-old db/db mice were administered metformin (260 mg/kg/d) continuously for 8 weeks. The normal control group (NC) and diabetic model group (DM) were set up simultaneously. Mice renal tubular epithelial cells (mRTECs) were cultured in vitro. The cells were randomly div...
Source: Frontiers in Pharmacology - June 23, 2022 Category: Drugs & Pharmacology Source Type: research

Acute Administration of Metformin Protects Against Neuronal Apoptosis Induced by Cerebral Ischemia-Reperfusion Injury via Regulation of the AMPK/CREB/BDNF Pathway
Metformin is a first-line anti-diabetic agent with a powerful hypoglycemic effect. Several studies have reported that metformin can improve the prognosis of stroke patients and that this effect is independent of its hypoglycemic effect; however, the specific mechanism remains unclear. In this research, we explored the effect and specific mechanism of metformin in cerebral ischemia-reperfusion (I/R) injury by constructing a transient middle cerebral artery occlusion model in vivo and a glucose and oxygen deprivation/reoxygenation (OGD/R) model in vitro. The results of the in vivo experiments showed that acute treatment with...
Source: Frontiers in Pharmacology - April 1, 2022 Category: Drugs & Pharmacology Source Type: research

Dapagliflozin alleviates cardiac fibrosis through suppressing EndMT and fibroblast activation via AMPK α/TGF-β/Smad signalling in type 2 diabetic rats
This study aimed to evaluate the effect of SGLT2 inhibitor dapagliflozin (DAPA) on DCM especially for cardiac fibrosis and explore the underlying mechanism. In vivo, the model of type 2 diabetic rats was built with high-fat feeding and streptozotocin injection. Untreated diabetic rats showed cardiac dysfunction, increased myocardial fibrosis and EndMT, which was attenuated after treatment with DAPA and metformin. In vitro, HUVECs and primary cardiac fibroblasts were treated with DAPA and exposed to high glucose (HG). HG-induced EndMT in HUVECs and collagen secretion of fibroblasts were markedly inhibited by DAPA. Up-regula...
Source: J Cell Mol Med - June 25, 2021 Category: Molecular Biology Authors: Jingjing Tian Mingjun Zhang Mengying Suo Dian Liu Xuyang Wang Ming Liu Jinyu Pan Tao Jin Fengshuang An 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 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

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

Resveratrol attenuates diabetes-associated cell centrosome amplification via inhibiting the PKC α-p38 to c-myc/c-jun pathway.
In conclusion, our results suggest that PKCα-p38 to c-myc/c-jun is the signaling pathway of the diabetes-associated centrosome amplification, and resveratrol attenuates the centrosome amplification by inhibiting this signaling pathway. PMID: 31844893 [PubMed - as supplied by publisher]
Source: Acta Biochimica et Biophysica Sinica - December 15, 2019 Category: Biochemistry Authors: Wu Q, Chen X, He Q, Lang L, Xu P, Wang P, Lee SC Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research

RasGRP1 is a target for VEGF to induce angiogenesis and involved in the endothelial ‐protective effects of metformin under high glucose in HUVECs
AbstractImpaired angiogenesis in endothelial cells is a hallmark of diabetes vascular complications. Ras guanine ‐releasing protein 1 (RasGRP1) is a guanine nucleotide exchange factor for Ras, and its role in endothelial angiogenesis has not been investigated. Given the importance of Ras in vascular endothelial growth factor (VEGF)‐induced angiogenesis, we hypothesized that RasGRP1 may be a critical pathwa y downstream of VEGF and involved in endothelial angiogenesis. Furthermore, we investigate whether RasGRP1‐dependent VEGF signaling was downregulated under high glucose conditions mimicking diabetes and required fo...
Source: IUBMB Life - May 22, 2019 Category: Research Authors: Jing Xu, Miao Liu, Muqiao Yu, Jiayi Shen, Jiecan Zhou, Jinglei Hu, Yong Zhou, Wei Zhang Tags: Research Communication Source Type: research

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