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Total 445 results found since Jan 2013.

Endothelial HMGB1 Is a Critical Regulator of LDL Transcytosis via an SREBP2-SR-BI Axis.
CONCLUSIONS: Endothelial HMGB1 regulates LDL transcytosis by prolonging the half-life of SREBP2, enhancing SR-BI expression. Translocation of HMGB1 to the nucleus in response to LDL requires SR-BI. PMID: 33054399 [PubMed - as supplied by publisher]
Source: Arteriosclerosis, Thrombosis and Vascular Biology - October 15, 2020 Category: Cardiology Authors: Ghaffari S, Jang E, Nabi FN, Sanwal R, Khosraviani N, Wang C, Steinberg BE, Goldenberg NM, Ikeda J, Lee WL Tags: Arterioscler Thromb Vasc Biol Source Type: research

SCAP Mediated GDF15-Induced Invasion and EMT of Esophageal Cancer
Conclusions: We demonstrated that SCAP mediated GDF15-induced the invasion and metastasis of EC by regulating cholesterol metabolism. In addition, GDF15 was shown to be a direct target of miR-1324.
Source: Frontiers in Oncology - October 5, 2020 Category: Cancer & Oncology Source Type: research

Caspase-11/4 and gasdermin D-mediated pyroptosis contributes to podocyte injury in mouse diabetic nephropathy.
In this study we investigated whether pyroptosis, a newly discovered cell death pathway was involved in DN. Diabetic mice were generated by high-fat diet/STZ injections. We showed that the expression levels of caspase-11 and cleavage of gasdermin D (GSDMD-N) in podocytes were significantly elevated, accompanied by reduced expression of podocyte makers nephrin and podocin, loss and fusion in podocyte foot processes, increased inflammatory cytokines NF-κB, IL-1β, and IL-18, macrophage infiltration, glomerular matrix expansion and increased urinary albumin to creatinine ratio (UACR). All these changes in diabetic mice were ...
Source: Acta Pharmacologica Sinica - September 22, 2020 Category: Drugs & Pharmacology Authors: Cheng Q, Pan J, Zhou ZL, Yin F, Xie HY, Chen PP, Li JY, Zheng PQ, Zhou L, Zhang W, Liu J, Lu LM Tags: Acta Pharmacol Sin Source Type: research

Kalirin-7 contributes to type 2 diabetic neuropathic pain via the postsynaptic density-95/N-methyl-D-aspartate receptor 2B-dependent N-methyl-D-aspartate receptor 2B phosphorylation in the spinal cord in rats.
CONCLUSIONS: Our findings suggest that spinally expressed Kalirin-7 likely contributes to type 2 diabetic neuropathic pain through regulating the PSD-95/NR2B interaction-dependent NR2B phosphorylation in the spinal cord. PMID: 32913553 [PubMed]
Source: American Journal of Translational Research - September 13, 2020 Category: Research Tags: Am J Transl Res Source Type: research

Improved Glucose Intolerance Through a Distinct Mouse Olfactory Receptor 23 ‐Induced Signaling Pathway Mediating Glucose Uptake In Myotubes and Adipocytes
ConclusionsThese findings suggest that MOR23 is a novel factor for the regulation of glucose uptake and whole ‐body glucose homeostasis and has therapeutic potential for diabetes treatment.This article is protected by copyright. All rights reserved
Source: Molecular Nutrition and Food Research - September 10, 2020 Category: Food Science Authors: Wesuk Kang, Kelun Zhang, Tao Tong, Taesun Park Tags: Research Article Source Type: research

Thioredoxin-interacting protein: a critical link between autophagy disorders and pancreatic β-cell dysfunction
This study aimed to elucidate the influence of TXNIP on the autophagy of β-cell. In this study, C57BL/6 mice and TXNIP−/− mice were fed with a standard diet (SD) or a high-fat and high-sugar diet (HFSD), and then we analysed biochemical and autophagy related indexes in the mice. We infected MIN6 cells with LV-TXNIP and siRNA TXNIP, then the cells were treated with free fatty acid (FFA), autophagic activator rapamycin (RAP), inhibitors of autophagy chloroquine (CQ) and bafilomycin A1(BAF), finally, we examined the changes of autophagy in MIN6 cells. The results showed that HFSD led to β-cell dysfunction and autophagy ...
Source: Endocrine - September 5, 2020 Category: Endocrinology Source Type: research

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1 –SIRT1–PGC-1α
Conclusions/interpretationOur findings showed that the APPL1 –SIRT1–PGC-1α pathway regulates the production and/or secretion of skeletal muscle MOTS-c by mediating adiponectin signalling. Our study provides an insight into the cellular and molecular pathways underlying the pathogenesis of diabetes and shows that MOTS-c is a potential novel therapeutic ta rget in the treatment of diabetes.Graphical abstract
Source: Diabetologia - September 2, 2020 Category: Endocrinology Source Type: research

GPR120 regulates pancreatic polypeptide secretion from male mouse islets via PLC-mediated calcium mobilization.
In this study, GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhance green fluorescence proteins (EGFP). EGFP-positive cells collected from the KI mouse islets by flow cytometry had significantly higher expression of pancreatic polypeptide (PP) evidenced by RT-qPCR. Single cell RT-PCR and immunocytochemical double staining also demonstrated the co-expression of GPR120 with PP in mouse islets. GPR120 specific agonist, TUG-891, significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR1...
Source: Endocrinology - September 1, 2020 Category: Endocrinology Authors: Zhao YF, Li XC, Liang XY, Zhao YY, Xie R, Zhang LJ, Zhang XC, Chen C Tags: Endocrinology Source Type: research

Nanoparticle-based "Two-pronged" approach to regress atherosclerosis by simultaneous modulation of cholesterol influx and efflux.
Abstract Reduction of lipoprotein uptake by macrophages and stimulation of cholesterol efflux are two essential steps required for atherosclerotic plaque regression. We used the optimized mannose-functionalized dendrimeric nanoparticle (mDNP)-based platform for macrophage-specific delivery of therapeutics to simultaneously deliver SR-A siRNA (to reduce LDL uptake) and LXR ligand (LXR-L, to stimulate cholesterol efflux) - a novel "Two-pronged" approach to facilitate plaque regression. mDNP-mediated delivery of SR-A siRNA led to a significant reduction in SR-A expression with a corresponding decrease in uptake of ox...
Source: Biomaterials - August 14, 2020 Category: Materials Science Authors: He H, Wang J, Yannie PJ, Korzun WJ, Yang H, Ghosh S Tags: Biomaterials Source Type: research

Endothelial Deficiency of Insulin-like Growth Factor -1 Receptor Reduces Endothelial Barrier Function and Promotes Atherosclerosis in Apoe-Deficient Mice.
Abstract Insulin-like growth factor-1 (IGF-1) decreases atherosclerosis in Apolipoprotein E (Apoe) -deficient mice when administered systemically. However, mechanisms for its atheroprotective effect are not fully understood. We generated endothelium-specific IGF-1 receptor (IGF1R) deficient mice on Apoe-deficient background to assess effects of IGF-1 on the endothelium in the context of hyperlipidemia-induced atherosclerosis. Endothelial deficiency of IGF1R promoted atherosclerotic burden, when animals were fed on high-fat diet for 12 weeks or normal chow for 12 months. Under normal chow feeding condition, the vas...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 13, 2020 Category: Physiology Authors: Higashi Y, Sukhanov S, Shai SY, Danchuk S, Snarski P, Li Z, Hou X, Hamblin MH, Woods TC, Wang M, Wang D, Yu H, Korthuis RJ, Yoshida T, Delafontaine P Tags: Am J Physiol Heart Circ Physiol Source Type: research

Geniposide alleviates diabetic nephropathy of mice through AMPK/SIRT1/NF- κB pathway.
The objective of this study was to explore the antidiabetic nephropathy effects of GE both in high fat diet/streptozotocin-induced DN mice and in high glucose-induced podocyte model. Renal function in DN mice was evaluated by levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Renal inflammation was appraised by pro-inflammatory cytokines: Tumor necrosis factor α (TNF-α), Interleukin 6 (IL-6) and IL-1β via ELISA assay. Renal histopathology analysis was conducted via hematoxylin and eosin, Masson and periodic acid-silver metheramine staining. Cellular viability was measured by Terminal deoxynucleotidyl transf...
Source: European Journal of Pharmacology - August 2, 2020 Category: Drugs & Pharmacology Authors: Li F, Chen Y, Li Y, Huang M, Zhao W Tags: Eur J Pharmacol Source Type: research

CoenzymeQ10-Induced Activation of AMPK-YAP-OPA1 Pathway Alleviates Atherosclerosis by Improving Mitochondrial Function, Inhibiting Oxidative Stress and Promoting Energy Metabolism
This study provides a possible new mechanism for CoQ10 in the treatment of AS and may bring a new hope for the prevention and treatment of AS in the future.
Source: Frontiers in Pharmacology - July 21, 2020 Category: Drugs & Pharmacology Source Type: research

Research Articles siRNA nanoparticles targeting CaMKII{gamma} in lesional macrophages improve atherosclerotic plaque stability in mice
Atherosclerotic lesional macrophages express molecules that promote plaque progression, but lack of mechanisms to therapeutically target these molecules represents a major gap in translational cardiovascular research. Here, we tested the efficacy of a small interfering RNA (siRNA) nanoparticle (NP) platform targeting a plaque-destabilizing macrophage molecule—Ca2+/calmodulin-dependent protein kinase (CaMKII). CaMKII becomes activated in advanced human and mouse plaque macrophages and drives plaque necrosis by suppressing the expression of the efferocytosis receptor MerTK. When macrophage-targeted siCamk2g NPs were ad...
Source: Science Translational Medicine - July 21, 2020 Category: Biomedical Science Authors: Tao, W., Yurdagul, A., Kong, N., Li, W., Wang, X., Doran, A. C., Feng, C., Wang, J., Islam, M. A., Farokhzad, O. C., Tabas, I., Shi, J. Tags: Research Articles Source Type: research

MAPK-interacting kinase 2 (MNK2) regulates adipocyte metabolism independently of its catalytic activity.
Abstract The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are serine/threonine protein kinases that are activated by the ERK1/2 (extracellular-regulated kinase) and p38α/β MAPK pathways. The MNKs have previously been implicated in metabolic disease and shown to mediate diet-induced obesity. In particular, knockout of MNK2 in mice protects from the weight gain induced by a high-fat diet. These and other data suggest that MNK2 regulates expansion of adipose tissue, a stable, long-term energy reserve that plays an important role in regulating whole-body energy homeostasis. Using the well-estab...
Source: The Biochemical Journal - July 9, 2020 Category: Biochemistry Authors: Merrett J, Xie J, Psaltis PJ, Proud CG Tags: Biochem J Source Type: research

Stimulatory Role of SPAK Signaling in the Regulation of Large Conductance Ca2+-Activated Potassium (BK) Channel Protein Expression in Kidney
In this study, we investigated the effect of SPAK on renal BK protein expression in both HEK293 cells and mouse kidney. In HEK293 cells, siRNA-mediated knockdown of SPAK expression significantly reduced BK protein expression and increased ERK1/2 phosphorylation, whereas overexpression of SPAK significantly enhanced BK expression and decreased ERK1/2 phosphorylation in a dose-dependent manner. Knockdown of ERK1/2 prevented SPAK siRNA-mediated inhibition of BK expression. Similarly, pretreatment of HEK293 cells with either the lysosomal inhibitor bafilomycin A1 or the proteasomal inhibitor MG132 reversed the inhibitory effec...
Source: Frontiers in Physiology - July 1, 2020 Category: Physiology Source Type: research