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Simvastatin  treatment promotes proliferation of human dental pulp stem cells via modulating PI3K/AKT/miR-9/KLF5 signalling pathway
J Cell Mol Med. 2021 Nov 19. doi: 10.1111/jcmm.16973. Online ahead of print.ABSTRACTSimvastatin serves as an effective therapeutic potential in the treatment of dental disease via alternating proliferation of dental pulp stem cells. First, western-blot and real-time quantitative PCR were used to detect the effect of simvastatin or LY294002 on the expression levels of AKT, miR-9 and KLF5, or determine the effect of miR-9. Simvastatin, KLF5 and AKT significantly enhanced the proliferation of pulp stem cells, whilst this effect induced by simvastatin was suppressed by LY294002, AKT siRNA, KLF5 siRNA and miR-9, and simvastatin...
Source: J Cell Mol Med - November 20, 2021 Category: Molecular Biology Authors: Jing-Hui Wang Dang-En He Source Type: research

Fight Aging! Newsletter, April 3rd 2023
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - April 2, 2023 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Inclisiran-Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9
Pharmaceutics. 2023 Jan 18;15(2):323. doi: 10.3390/pharmaceutics15020323.ABSTRACTDyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis of lipid-lowering therapy. Nevertheless, these drugs are often insufficient due to their side effects and restrictive criteria for achieving the recommended LDL-C values. Even the addition of other drugs, i.e., ezetimibe, does not help one achieve th...
Source: Atherosclerosis - February 25, 2023 Category: Cardiology Authors: Łukasz Wołowiec Joanna Osiak Anna Wo łowiec Aleksandra Wijata El żbieta Grześk Mariusz Kozakiewicz Joanna Banach Alicja Nowaczyk Jacek Nowaczyk Grzegorz Grze śk Source Type: research

New cholesterol drug shows promise
Conclusion Media headlines reporting on this phase I trial concentrated on the secondary outcome (that ALN-PCS reduced LDL cholesterol levels). However, these results will need to be confirmed during phase II and phase III clinical trials, which will involve more participants who would normally receive cholesterol-lowering treatment. While it is tempting to focus on the results of the cholesterol levels, phase I clinical trials are designed to test the safety of a new drug to make sure it is safe enough to test further. They also aim to determine what the highest tolerable dose is, so the appropriate one can be used in la...
Source: NHS News Feed - October 3, 2013 Category: Consumer Health News Tags: Heart/lungs Medical practice Medication Source Type: news

Simvastatin prevents neuroinflammation by inhibiting N‐methyl‐D‐aspartic acid receptor 1 in 6‐hydroxydopamine‐treated PC12 cells
This study investigates the impact of simvastatin on neuroinflammation in experimental parkinsonian cell models. 6‐Hydroxydopamine (6‐OHDA)‐treated pheochromocytoma‐12 (PC12) cells were used to investigate the neuroprotective nature of simvastatin. After incubation with 6‐OHDA, simvastatin, and/or N‐methyl‐D‐aspartic acid receptor 1 (NMDAR1) siRNA for 24 hr, test kits were used to detect the levels of lactate dehydrogenase (LDH) and glutamate released from PC12 cells exposed to different culture media. The mRNA levels of tumor necrosis factor (TNF)‐α, interleukin (IL)−1β, and IL‐6 were determined by...
Source: Journal of Neuroscience Research - January 31, 2014 Category: Neuroscience Authors: Junqiang Yan, Jiachun Sun, Lina Huang, Qizhi Fu, Ganqin Du Tags: Research Article Source Type: research

New CETP Inhibitor K-312 Reduces PCSK9 Expression: A Potential Effect on LDL Cholesterol Metabolism.
Abstract Despite significant reduction of cardiovascular events by statin treatment, substantial residual risk persists, driving emerging needs for the development of new therapies. We identified a novel cholesteryl ester transfer protein (CETP) inhibitor, K-312, that raises HDL- and lowers LDL-cholesterol levels in animals. K-312 also suppresses hepatocyte expression of proprotein convertase subtilisin/kexin 9 (PCSK9), a molecule that increases LDL cholesterol. We explored the underlying mechanism for the reduction of PCSK9 expression by K-312. K-312 inhibited in vitro human plasma CETP activity (IC50: 0.06 μM)....
Source: Am J Physiol Endocri... - May 26, 2015 Category: Endocrinology Authors: Miyosawa K, Watanabe Y, Murakami K, Murakami T, Shibata H, Iwashita M, Yamazaki H, Yamazaki K, Ohgiya T, Shibuya K, Mizuno K, Tanabe S, Singh SA, Aikawa M Tags: Am J Physiol Endocrinol Metab Source Type: research

New CETP inhibitor K-312 reduces PCSK9 expression: a potential effect on LDL cholesterol metabolism
Despite significant reduction of cardiovascular events by statin treatment, substantial residual risk persists, driving emerging needs for the development of new therapies. We identified a novel cholesteryl ester transfer protein (CETP) inhibitor, K-312, that raises HDL and lowers LDL cholesterol levels in animals. K-312 also suppresses hepatocyte expression of proprotein convertase subtilisin/kexin 9 (PCSK9), a molecule that increases LDL cholesterol. We explored the underlying mechanism for the reduction of PCSK9 expression by K-312. K-312 inhibited in vitro human plasma CETP activity (IC50; 0.06 μM). Administration o...
Source: AJP: Endocrinology and Metabolism - July 15, 2015 Category: Endocrinology Authors: Miyosawa, K., Watanabe, Y., Murakami, K., Murakami, T., Shibata, H., Iwashita, M., Yamazaki, H., Yamazaki, K., Ohgiya, T., Shibuya, K., Mizuno, K., Tanabe, S., Singh, S. A., Aikawa, M. Tags: Articles Source Type: research

Fight Aging! Newsletter, November 8th 2021
In conclusion, in less common and visible cardiovascular diseases, it is crucial to recognize substantial progress and achievement, given that penetration of such information into clinical practice and the patient community can be inconsistent. Diseases such as hypertrophic cardiomyopathy, pulmonary arterial hypertension, and ATTR cardiac amyloidosis, once linked to a uniformly adverse prognosis, are now associated with the opportunity for patients to experience satisfactory quality of life and extended longevity. VitaDAO, a Novel Approach to Crowdfunding Life Science Research https://www.fightaging.org/archive...
Source: Fight Aging! - November 7, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Inclisiran: A Novel Small Interfering RNA Drug for LDL Reduction
This article is protected by copyright. All rights reserved.PMID:35279835 | DOI:10.1002/jcph.2045
Source: The Journal of Clinical Pharmacology - March 13, 2022 Category: Drugs & Pharmacology Authors: Kimberly W Smith C Michael White Source Type: research

Estrogen receptor mediates simvastatin-stimulated osteogenic effects in bone marrow mesenchymal stem cells.
In this study, we hypothesize that the estrogen receptor (ER) mediates simvastatin-induced osteogenic differentiation. ER antagonists and siRNA were used to determine the involvement of the ER in simvastatin-induced osteogenesis in mouse bone marrow mesenchymal stem cells (D1 cells). Osteogenesis was evaluated by mRNA expression, protein level/activity of osteogenic markers, and mineralization. The estrogen response element (ERE) promoter activity and the ER-simvastatin binding affinity were examined. Our results showed that the simvastatin-induced osteogenic effects were decreased by treatment with ERα antagonists and ER...
Source: Biochemical Pharmacology - September 24, 2015 Category: Drugs & Pharmacology Authors: Chuang SC, Chen CH, Fu YC, Tai IC, Li CJ, Chang LF, Ho ML, Chang JK Tags: Biochem Pharmacol Source Type: research

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch.
Abstract MURC (muscle-restricted coiled-coil protein) is a hypertrophy-related gene. Hypertrophy can be induced by mechanical stress. The purpose of this research was to investigate the hypothesis that MURC mediates hypertrophy in cardiomyocytes under mechanical stress. We used the in vivo model of an aortocaval shunt (AV shunt) in adult Wistar rats to induce myocardial hypertrophy. We also used the in vitro model of cyclic stretch in rat neonatal cardiomyocytes to clarify MURC expression and the molecular regulation mechanism. The flexible membrane culture plate seeding with cardiomyocytes Cardiomyocytes seeded o...
Source: J Cell Mol Med - December 3, 2018 Category: Molecular Biology Authors: Cheng WP, Lo HM, Wang BW, Chua SK, Shyu KG Tags: J Cell Mol Med Source Type: research

Combination simvastatin and metformin synergistically inhibits endometrial cancer cell growth.
CONCLUSIONS: MET+SIM treatment synergistically inhibits endometrial cancer cell viability. This may be mediated by apoptosis and mTOR pathway inhibition. Our results provide preclinical evidence that the combination of these well-tolerated drugs may warrant further clinical investigation for endometrial cancer treatment. PMID: 31178149 [PubMed - as supplied by publisher]
Source: Gynecologic Oncology - June 5, 2019 Category: Cancer & Oncology Authors: Kim JS, Turbov J, Rosales R, Thaete LG, Rodriguez GC Tags: Gynecol Oncol Source Type: research

Novel function of fluvastatin in attenuating oxidized low-density lipoprotein-induced endothelial cell ferroptosis in a glutathione peroxidase4- and cystine-glutamate antiporter-dependent manner
Exp Ther Med. 2021 Nov;22(5):1275. doi: 10.3892/etm.2021.10710. Epub 2021 Sep 8.ABSTRACTOxidized low-density lipoprotein (ox-LDL) induces endothelial cell apoptosis and dysfunction. Statins are drugs that are clinically used to lower serum cholesterol levels, and they have been shown to exert vascular protective effects. In the present study, human umbilical vein endothelial cells were transfected with scramble control siRNA or siRNA specific for glutathione peroxidase (GPx)4 or cystine-glutamate antiporter (xCT). MTT, Matrigel and Transwell assays were used to evaluate cell proliferation, tube formation and migration, res...
Source: Experimental and Therapeutic Medicine - October 1, 2021 Category: General Medicine Authors: Qing Li Chang Liu Liang Deng Enrui Xie Nishant Yadav Yuanyuan Tie Zheng Cheng Jie Deng Source Type: research