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HMG coA reductase

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https://www.readbyqxmd.com/read/28916945/simvastatin-enhances-radiation-sensitivity-of-colorectal-cancer-cells
#1
Georgios Karagkounis, Jennifer DeVecchio, Sylvain Ferrandon, Matthew F Kalady
INTRODUCTION: Neoadjuvant chemoradiation (CRT) for rectal cancer induces variable responses, and better response has been associated with improved oncologic outcomes. Our group has previously shown that the administration of HMG-CoA reductase inhibitors, commonly known as statins, is associated with improved response to neoadjuvant CRT in rectal cancer patients. The purpose of this study was to study the effects of simvastatin on colorectal cancer cells and explore its potential as a radiation-sensitizer in vitro...
September 15, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28903412/acute-atorvastatin-treatment-restores-the-cardioprotective-effects-of-ischemic-postconditioning-in-hyperlipidemic-rats
#2
Tao Sun, Hong-Ju Zhang, Chayakrit Krittanawong, Su Wang, Ying Tao, Zhao Li, Qiancheng Yin, Donghua Zhang, Qian Wang, Ji Huang, Jingmei Zhang, Zhizhong Li, Yutong Cheng
BACKGROUND: Ischemic Postconditioning (IPC) reduces ischemia/reperfusion (I/R) injury under normal conditions. HMG-CoA reductase inhibitors (statins), which inhibit the synthesis of mevalonate, can interfere with the cardioprotective effect of IPC. However, the beneficial role of IPC in hyperlipidemic patients, post-acute administration of statins remains unknown. This study was to determine if acute administration of atorvastatin affect the infarct size-limiting effect of IPC in hyperlipidemic rats...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881801/a-screen-for-inducers-of-bhlh-activity-identifies-pitavastatin-as-a-regulator-of-p21-rb-phosphorylation-and-e2f-target-gene-expression-in-pancreatic-cancer
#3
Nicholas Villarino, Lia Signaevskaia, Jaco van Niekerk, Rachel Medal, Heejung Kim, Reyhaneh Lahmy, Kathleen Scully, Anthony Pinkerton, Sangwun Kim, Andrew Lowy, Pamela Itkin-Ansari
The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875055/pilot-algorithm-designed-to-help-early-detection-of-hmg-coa-reductase-inhibitor-induced-hepatotoxicity
#4
Joo Young Hong, Hun-Sung Kim, In Young Choi
OBJECTIVES: To enable early detection of adverse drug reactions (ADRs) in patients using HMG-CoA reductase inhibitors (statins), we developed an algorithm that automatically detects liver injury caused by statins from Electronic Medical Record (EMR) data. We verified the performance of our algorithm through manual ADR assessment and a direct chart review. METHODS: The subjects in this study were patients who had been prescribed a statin for the first time among outpatients in Seoul St...
July 2017: Healthcare Informatics Research
https://www.readbyqxmd.com/read/28869702/the-prevalence-and-preventability-of-potentially-relevant-drug-drug-interactions-in-patients-admitted-for-cardiovascular-diseases-a-cross-sectional-study
#5
Milena Kovačević, Sandra Vezmar Kovačević, Branislava Miljković, Slavica Radovanović, Predrag Stevanović
AIM: The aim was to describe the type and prevalence of potentially relevant drug-drug interactions (pDDIs) in a population of patients admitted for cardiovascular diseases (CVD), and management strategies for reducing the occurrence of pDDIs. METHODS: A retrospective cross-sectional study was performed on Cardiology ward of University Clinical Hospital Center in Belgrade, Serbia. A total of 527 patients, with more than one prescription during hospital stay, were enrolled in this study...
September 4, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28864210/inhibition-of-the-mevalonate-pathway-by-simvastatin-interferes-with-mast-cell-degranulation-by-disrupting-the-interaction-between-rab27a-and-double-c2-alpha-proteins
#6
Muhammad Novrizal Abdi Sahid, Shuang Liu, Takeshi Kiyoi, Kazutaka Maeyama
Statins are well-known inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which block the mevalonate pathway. The activity of statins not only decreases cholesterol levels but also ameliorates inflammation and modulates the immune system. In this study, we investigated the effects of simvastatin on histamine release using rat basophilic leukaemia (RBL-2H3) cells, and examined its interaction with proteins involved in the exocytosis process. Treatment with simvastatin for 24h inhibited histamine release in RBL-2H3 cells in a concentration-dependent manner after stimulation with dinitrophenylated bovine serum albumin (DNP-BSA, as an antigen), ionomycin (a calcium ion [Ca(2+)] ionophore), and thapsigargin (an inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum)...
August 29, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28859294/ccaat-enhancer-binding-protein-delta-promotes-intracellular-lipid-accumulation-in-m1-macrophages-of-vascular-lesions
#7
Hong-Yue Lai, Ling-Wei Hsu, Hsin-Hwa Tsai, Yu-Chih Lo, Shang-Hsun Yang, Ping-Yen Liu, Ju-Ming Wang
Aims: Lipid homeostasis is reprogrammed in the presence of inflammation, which results in excessive lipid accumulation in macrophages, and leads to the formation of lipid-laden foam cells. We aimed to link an inflammation-responsive transcription factor CCAAT/enhancer-binding protein delta (CEBPD) with polarized macrophages and dissect its contribution to lipid accumulation. Methods and results: We found that CEBPD protein colocalized with macrophages in human and mouse (C57BL/6, Apoe-/-) atherosclerotic plaques and that Cebpd deficiency in bone marrow cells suppressed atherosclerotic lesions in hyperlipidemic Apoe-/- mice...
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28846702/association-between-statin-use-the-vaginal-microbiome-and-gardnerella-vaginalis-vaginolysin-mediated-cytotoxicity
#8
Abdallah A Abdelmaksoud, Philippe H Girerd, Erin M Garcia, J Paul Brooks, Lauren M Leftwich, Nihar U Sheth, Steven P Bradley, Myrna G Serrano, Jennifer M Fettweis, Bernice Huang, Jerome F Strauss, Gregory A Buck, Kimberly K Jefferson
BACKGROUND: Bacterial vaginosis (BV) is the leading dysbiosis of the vaginal microbiome. The pathways leading towards the development of BV are not well understood. Gardnerella vaginalis is frequently associated with BV. G. vaginalis produces the cholesterol-dependent cytolysin (CDC), vaginolysin, which can lyse a variety of human cells and is thought to play a role in pathogenesis. Because membrane cholesterol is required for vaginolysin to function, and because HMG-CoA reductase inhibitors (statins) affect not only serum levels of cholesterol but membrane levels as well, we hypothesized that statins might affect the vaginal microbiome...
2017: PloS One
https://www.readbyqxmd.com/read/28845666/regeneration-of-nadph-coupled-with-hmg-coa-reductase-activity-increases-squalene-synthesis-in-saccharomyces-cerevisiae
#9
Kalaivani Paramasivan, Sarma Mutturi
Although overexpression of the tHMG1 gene is a well-known strategy for terpene synthesis in Saccharomyces cerevisiae, the optimal level for tHMG1p has not been established. In the present study, it was observed that two copies of the tHMG1 gene on a dual gene expression cassette improved squalene synthesis in laboratory strain by 16.8-fold in comparison to single-copy expression. It was also observed that tHMG1p is limited by its cofactor (NADPH), as the overexpression of NADPH regenerating genes', viz., ZWF1 and POS5 (full length and without mitochondrial presequence), has led to its increased enzyme activity...
September 6, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28843826/zoledronic-acid-an-fpps-inhibitor-ameliorates-liver-steatosis-through-inhibiting-hepatic-de-novo-lipogenesis
#10
Qiaoli Tang, Shan Jiang, Wenjun Jia, Di Shen, Yudong Qiu, Yue Zhao, Bin Xue, Chaojun Li
Currently, there is no standard therapy for non-alcoholic fatty liver disease (NAFLD), and statins have been developed as a first-line pharmaceutical therapeutic option for NAFLD-associated dyslipidemia. However, prolonged statins therapy has side effects, as statins inhibit HMG-CoA reductase, an enzyme at the very beginning of the mevalonate pathway. Here, we found that zoledronic acid (ZA), an inhibitor of farnesyl diphosphate synthase in the downstream mevalonate pathway, could attenuate hepatic lipid accumulation and improve liver injury in both high-fat diet-induced C57BL/6J mice and ob/ob mice...
August 24, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28840430/mevastatin-promotes-neuronal-survival-against-a%C3%AE-induced-neurotoxicity-through-ampk-activation
#11
Edy Kornelius, Hsin-Hua Li, Chiung-Huei Peng, Hui-Wen Hsiao, Yi-Sun Yang, Chien-Ning Huang, Chih-Li Lin
Statins or HMG-CoA reductase inhibitors have been shown to be effective at lowering cholesterol levels, and the application of these molecules has gradually emerged as an attractive therapeutic strategy for neurodegenerative diseases. Epidemiological studies suggest that statin use is associated with a decreased incidence of Alzheimer's disease (AD). Thus, statins may play a beneficial role in reducing amyloid β (Aβ) toxicity, the most relevant pathological feature and pathogenesis of AD. However, the precise mechanisms involved in statin-inhibited Aβ toxicity remain unclear...
August 24, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28820396/the-role-of-mtor-inhibitors-and-hmg-coa-reductase-inhibitors-on-young-and-old-endothelial-cell-functions-critical-for-re-endothelialisation-after-percutaneous-coronary-intervention-an-in-vitro-study
#12
K Korybalska, E Kawka, A Breborowicz, J Witowski
Percutaneous coronary intervention (PCI) has become a standard treatment in patients with acute coronary syndrome. However, it is associated with endothelial cell denudation, which may predispose to in-stent thrombosis and restenosis. Pharmacological methods which prevent restenosis can delay post-PCI re-endothelialisation. We have therefore examined how atorvastatin (HMG-CoA reductase inhibitor), sirolimus and everolimus (mTOR inhibitors) affect young and old endothelial cell functions which are responsible for wound healing after PCI...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28812326/effect-of-dietary-components-from-antarctic-krill-on-atherosclerosis-in-apoe-deficient-mice
#13
Cinzia Parolini, Bodil Bjorndal, Marco Busnelli, Stefano Manzini, Giulia S Ganzetti, Federica Dellera, Marie Ramsvik, Inge Bruheim, Rolf Kristian Berge, Giulia Chiesa
SCOPE: Antarctic krill is a great source of n-3 fatty acids and high-quality proteins. Aim of the study was to evaluate the effect of Antarctic krill components on plasma lipids and atherosclerosis development. METHODS AND RESULTS: Sixty apoEKO mice were divided into four groups and fed Western diet (CONTROL) or Western-like diets, differing for protein or fat content. Specifically, casein or fat in CONTROL was partially replaced by krill proteins (PRO), krill oil (KRILL OIL), or both (KRILL OIL+PRO)...
August 15, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28808476/bark-extracts-of-ceylon-cinnamon-possess-antilipidemic-activities-and-bind-bile-acids-in-vitro
#14
Walimuni Prabhashini Kaushalya Mendis Abeysekera, Sirimal Premakumara Galbada Arachchige, Wanigasekera Daya Ratnasooriya
Ethanol (95%) and dichloromethane : methanol (1 : 1) bark extracts of authenticated Ceylon cinnamon were investigated for range of antilipidemic activities (ALA): HMG-CoA reductase, lipase, cholesterol esterase, and cholesterol micellization inhibitory activities and bile acids binding in vitro. Individual compounds in bark extracts were also evaluated. Bark extracts showed ALA in all the assays studied. The IC50 (μg/mL) values ranged within 153.07 ± 8.38-277.13 ± 32.18, 297.57 ± 11.78-301.09 ± 4...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28796249/rho-inhibition-by-lovastatin-affects-apoptosis-and-dsb-repair-of-primary-human-lung-cells-in-vitro-and-lung-tissue-in-vivo-following-fractionated-irradiation
#15
Verena Ziegler, Christian Henninger, Ioannis Simiantonakis, Marcel Buchholzer, Mohammad Reza Ahmadian, Wilfried Budach, Gerhard Fritz
Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28771594/patients-experiencing-statin-induced-myalgia-exhibit-a-unique-program-of-skeletal-muscle-gene-expression-following-statin-re-challenge
#16
Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago R Vera, Hannah Fish-Trotter, Robert W Williams, Richard D Childress, Rajendra Raghow
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls...
2017: PloS One
https://www.readbyqxmd.com/read/28745862/glcnac-conjugated-atorvastatin-with-enhanced-water-solubility-and-cellular-internalization
#17
Xinfu Zhang, Xiaofang Chen, Weiyu Zhao, Chunxi Zeng, Xiao Luo, Wenqing Li, Bin Li, Justin Jiang, Yizhou Dong
Targeting ligands facilitate cell specific drug delivery and improve pharmaceutical properties. Herein, we designed two ligand drug conjugates by conjugating GlcNAc (N-acetylglucosamine) with atorvastatin. These two conjugates, termed G-AT and G-K-AT, exhibited enhanced water solubility and cellular uptake. Moreover, both G-AT and G-K-AT were able to release atorvastatin and consequently achieve significant inhibition against 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase.
August 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28732362/acute-atorvastatin-treatment-restores-the-cardioprotective-effects-of-ischemic-postconditioning-in-hyperlipidemic-rats
#18
Tao Sun, Hong-Ju Zhang, Chayakrit Krittanawong, Su Wang, Ying Tao, Zhao Li, Qiancheng Yin, Donghua Zhang, Qian Wang, Ji Huang, Jingmei Zhang, Zhizhong Li, Yutong Cheng
BACKGROUND: Ischemic Postconditioning (IPC) reduces ischemia/reperfusion (I/R) injury under normal conditions. HMG-CoA reductase inhibitors (statins), which inhibit the synthesis of mevalonate, can interfere with the cardioprotective effect of IPC. However, the beneficial role of IPC in hyperlipidemic patients, post-acute administration of statins remains unknown. This study was to determine if acute administration of atorvastatin affect the infarct size-limiting effect of IPC in hyperlipidemic rats...
July 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731315/hypocholesterolemic-activity-of-cornelian-cherry-cornus-mas-l-fruits
#19
Fatemeh Hosseinpour, Tahoora Shomali, Mahmoud Rafieian-Kopaei
Background Lipid profile disturbances are important risk factors for cardiovascular events in patients with diabetes mellitus and finding safe and multifaceted agents is persuaded in this regard. This study aimed to evaluate the effect of cornelian cherry dried powder (CCDP) on serum lipid profile as well as liver antioxidant capacity, HMG-CoA reductase level and activity, and LDL receptor level in streptozotocin-induced diabetic rats. Methods Forty-eight male adult Wistar rats were randomly allocated into eight equal groups and were treated for 4 weeks as follows: negative control (normal rats, basic diet); positive control (diabetic rats, basic diet), T1 to T4 groups: diabetic rats fed with basic diet containing 0...
June 1, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28729731/anti-asthmatic-effect-of-pitavastatin-through-aerosol-inhalation-is-associated-with-cd4-cd25-foxp3-t-cells-in-an-asthma-mouse-model
#20
Songquan Wu, Ruhui Yang, Guangli Wang
Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-A) reductase, and studies have shown that statins also have anti-inflammatory and immunomodulatory properties. The purpose of this study was to investigate the anti-asthmatic effects of pitavastatin, a type of statin, in an asthma mouse model. Mice were sensitized and challenged with ovalbumin (OVA) to establish the asthma model. These mice were then treated with inhaled pitavastatin (5 mg/kg) or dexamethasone (2 mg/kg), the latter of which served as a positive control...
July 20, 2017: Scientific Reports
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