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Total 281 results found since Jan 2013.
Hypercholesterolemia and 27-Hydroxycholesterol Increase S100A8 and RAGE Expression in the Brain: a Link Between Cholesterol, Alarmins, and Neurodegeneration
We report that a high-fat/high-cholesterol diet leads to an i ncrease in S100A8 production in the brain. In CYP27Tg, we report an increase of S100A8 and its receptor RAGE in the hippocampus under elevated 27-OH in the brain. Using siRNA, we found that 27-OH upregulation of RAGE in astrocytes and neurons is mediated by the nuclear receptor RXRγ. Silencing RXRγ in neurons prevented 27-OH-mediated upregulation of RAGE. These results show that S100A8 alarmin and RAGE respond to high levels of 27-OH in the brain in both neurons and astrocytes through RXRγ. Our study supports the notion that 27-OH mediates detrimental effects...
Source: Molecular Neurobiology - August 27, 2021 Category: Neurology Source Type: research
Thymosin beta 4 alleviates non-alcoholic fatty liver by inhibiting ferroptosis via up-regulation of GPX4
This study revealed that Tβ4 protects hepatocytes by inhibiting the GPX4-mediated ferroptosis pathway, which provides a new strategy and target for the treatment of NAFLD.PMID:34280397 | DOI:10.1016/j.ejphar.2021.174351
Source: European Journal of Pharmacology - July 19, 2021 Category: Drugs & Pharmacology Authors: Zixin Zhu Ya Zhang Xinhao Huang Li Can Xueke Zhao Yinghui Wang Jing Xue Mingliang Cheng Lili Zhu Source Type: research
Silencing of RSPO1 mitigates obesity-related renal fibrosis in mice by deactivating Wnt/ β-catenin pathway
Exp Cell Res. 2021 Jun 25:112713. doi: 10.1016/j.yexcr.2021.112713. Online ahead of print.ABSTRACTObesity, a global epidemic, is one of the critical causes of chronic kidney disease (CKD). R-spondin1 (RSPO1) possessing the potential to activate Wnt/β-catenin pathway was reported to be elevated in circulation of obesity objects. However, the function of RSPO1 and the latent mechanism in obesity-related CKD are still left to be revealed. In the present study, renal RSPO1 expression was increased in mice fed on high-fat diet (HFD) for 12 weeks. Lentivirus-mediated RSPO1 knockdown partly recovered obesity-related metabolic sy...
Source: Experimental Cell Research - June 28, 2021 Category: Cytology Authors: Xuesong Su Guangyu Zhou Mi Tian Si Wu Yanqiu Wang 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
Research Articles Hepatocyte TLR4 triggers inter-hepatocyte Jagged1/Notch signaling to determine NASH-induced fibrosis
Aberrant hepatocyte Notch activity is critical to the development of nonalcoholic steatohepatitis (NASH)–induced liver fibrosis, but mechanisms underlying Notch reactivation in developed liver are unclear. Here, we identified that increased expression of the Notch ligand Jagged1 (JAG1) tracked with Notch activation and nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in human liver biopsy specimens and mouse NASH models. The increase in Jag1 was mediated by hepatocyte Toll-like receptor 4 (TLR4)–nuclear factor B (NF-B) signaling in pericentral hepatocytes. Hepatocyte-specific Jag1 overexpression ex...
Source: Science Translational Medicine - June 23, 2021 Category: Biomedical Science Authors: Yu, J., Zhu, C., Wang, X., Kim, K., Bartolome, A., Dongiovanni, P., Yates, K. P., Valenti, L., Carrer, M., Sadowski, T., Qiang, L., Tabas, I., Lavine, J. E., Pajvani, U. B. Tags: Research Articles Source Type: research
Inhibition of CDK9 attenuates atherosclerosis by inhibiting inflammation and phenotypic switching of vascular smooth muscle cells
CONCLUSION: These results indicate that inhibition of CDK9 may be a novel therapeutic target for the prevention of atherosclerosis.PMID:34102609 | DOI:10.18632/aging.202998
Source: Aging - June 8, 2021 Category: Biomedical Science Authors: Shushi Huang Wu Luo Gaojun Wu Qirui Shen Zaishou Zhuang Daona Yang Jinfu Qian Xiang Hu Yan Cai Nipon Chattipakorn Weijian Huang Guang Liang Source Type: research
Patchouli alcohol improves wound healing in high fat diet-fed mice through AMPK-mediated suppression of inflammation and TGFb1 signaling
Biochem Biophys Res Commun. 2021 May 20;561:136-142. doi: 10.1016/j.bbrc.2021.05.036. Online ahead of print.ABSTRACTObesity impairs wound healing with substantial alterations in skin inflammation. Patchouli alcohol (PA), extracted from patchouli, has been reported to ameliorate inflammation in various cell types. However, the effects of PA on inflammation and wound healing have not been reported to date. In the present study, we examined whether PA affects cutaneous wound healing in high fat diet (HFD)-fed mice and explored PA-mediated molecular mechanisms through in vitro experiments. We found that PA administration accel...
Source: Biochemical and Biophysical Research communications - May 23, 2021 Category: Biochemistry Authors: Tae Jin Kim Do Hyeon Pyun Seung Yeon Park Hyun Jung Lee A M Abd El-Aty Jin-Ho Song Yong Kyoo Shin Ji Hoon Jeong Tae Woo Jung Source Type: research
Lipotoxicity reduces DDX58/Rig-1 expression and activity leading to impaired autophagy and cell death
This study uncovers the unexpected role of immune surveillance protein DDX58/Rig-1 (DExD/H box helicase 58) in activating macroautophagy/autophagy and protecting from lipotoxicity associated with NAFLD. Here we show for the first time that DDX58 protein is significantly reduced in nonalcoholic steatohepatitis (NASH) mouse model, an aggressive form of NAFLD characterized by inflammation and fibrosis of the liver. In addition to decreased expression of DDX58, we found that DDX58 activity can be attenuated by treatments with palmitic acid (PA), a saturated fatty acid. To investigate whether PA inhibition of DDX58 is harmful t...
Source: Autophagy - May 10, 2021 Category: Cytology Authors: Karla K Frietze Alyssa M Brown Dividutta Das Raymond G Franks Jessie Lee Cunningham Michael Hayward Joseph T Nickels Source Type: research
NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway
Diabetes increases the risk of stroke, exacerbates neurological deficits, and increases mortality. Non-mitogenic fibroblast growth factor 1 (nmFGF1) is a powerful neuroprotective factor that is also regarded as a metabolic regulator. The present study aimed to investigate the effect of nmFGF1 on the improvement of functional recovery in a mouse model of type 2 diabetic (T2D) stroke. We established a mouse model of T2D stroke by photothrombosis in mice that were fed a high-fat diet and injected with streptozotocin (STZ). We found that nmFGF1 reduced the size of the infarct and attenuated neurobehavioral deficits in our mous...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research
A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation
This study aimed to investigate if CCL4 could be a potential target to improve blood sugar control in different experimental DM models. Streptozotocin-induced diabetic mice, Leprdb/JNarl diabetic mice, and C57BL/6 mice fed a high fat diet were used as the type 1 DM, type 2 DM, and metabolic syndrome model individually. Mice were randomly assigned to receive an anti-CCL4 neutralizing monoclonal antibody. The pancreatic β-cells were treated with streptozotocin for in vitro experiments. In streptozotocin-induced diabetic mice, inhibition of CCL4 controlled blood sugar, increased serum insulin levels, increased islet cell pro...
Source: Frontiers in Immunology - April 23, 2021 Category: Allergy & Immunology Source Type: research
