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https://www.readbyqxmd.com/read/28089347/virtual-screening-and-experimental-validation-identify-novel-modulators-of-nuclear-receptor-rxr%C3%AE-from-drugbank-database
#1
Dan Xu, Lijun Cai, Shangjie Guo, Lei Xie, Meimei Yin, Ziwen Chen, Hu Zhou, Ying Su, Zhiping Zeng, Xiaokun Zhang
Retinoid X receptor alpha (RXRα), an important ligand-dependent transcription factor, plays a critical role in the development of various cancers and metabolic and neurodegenerative diseases. Therefore, RXRα represents one of the most important targets in modern drug discovery. In this study, Drugbank 2.0 with 1280 old drugs were virtually screened by Glide according to the crystal structure of ligand-binding domain (LBP) of RXRα. 15 compounds selected were tested for their binding and transcriptional activity toward RXRα by Biacore and reporter gene assay, respectively...
December 26, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28073164/protective-role-of-endogenous-plasmalogens-against-hepatic-steatosis-and-steatohepatitis
#2
Jung Eun Jang, Han-Sol Park, Hyun Ju Yoo, In-Jeoung Baek, Ji Eun Yoon, Myoung Seok Ko, Ah-Ram Kim, Hyoun Sik Kim, Hye-Sun Park, Seung Eun Lee, Seung-Whan Kim, Su Jung Kim, Jaechan Leem, Yu Mi Kang, Min Kyo Jung, Chan-Gi Pack, Chong Jai Kim, Chang Ohk Sung, In-Kyu Lee, Joong-Yeol Park, José C Fernández-Checa, Eun Hee Koh, Ki-Up Lee
: Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear. In this study, we found that hepatic levels of docosahexaenoic acid (DHA)-containing plasmalogens, expression of glyceronephosphate O-acyltransferase (Gnpat, the rate-limiting enzyme in plasmalogen biosynthesis), and expression of Pparα were lower in mice with NASH caused by accumulation of free cholesterol (FC) in the liver...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28013371/the-effect-of-fluvastatin-on-cardiac-fibrosis-and-angiotensin-converting-enzyme-2-expression-in-glucose-controlled-diabetic-rat-hearts
#3
Young Hee Shin, Jeong Jin Min, Jong-Hwan Lee, Eun-Hee Kim, Go Eun Kim, Myung Hee Kim, Jeong Jin Lee, Hyun Joo Ahn
Independently of the lipid-lowering effects, statin has been reported to attenuate the development of diabetic cardiomyopathy. However, the effect of statin in glucose-controlled diabetic condition has not been demonstrated. We evaluated the effect of fluvastatin on cardiac function, fibrosis, and angiotensin-converting enzyme-2 (ACE2) expression in glucose-controlled diabetic rats. Male Wistar rats were randomly divided into four groups: control (Group C), diabetes (Group D), diabetes with insulin (Group I), and diabetes with insulin and fluvastatin (Group I+F)...
December 24, 2016: Heart and Vessels
https://www.readbyqxmd.com/read/28012835/impaired-endothelial-function-and-arterial-stiffness-in-patients-with-type-2-diabetes-the-effect-of-a-very-low-dose-combination-of-fluvastatin-and-valsartan
#4
Maja Boncelj Svetek, Barbara Eržen, Karin Kanc, Mišo Šabovič
AIM: Patients with type 2 diabetes are at increased cardiovascular risk. The aim was to explore whether the impaired arterial wall characteristics typical of these patients could be improved by the unique beneficial effects of a very low-dose combination of fluvastatin and valsartan (low-flu/val). METHODS: Forty middle-aged males (50.4±6.1years) with type 2 diabetes were recruited to a double-blind, randomized study. Patients (N=20) received low-flu/val (10/20mg) or placebo (N=20) over 30days in addition to their regular therapy...
December 16, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28011020/environmental-photochemical-fate-of-selected-pharmaceutical-compounds-in-natural-and-reconstituted-suwannee-river-water-role-of-reactive-species-in-indirect-photolysis
#5
Hanoz Santoke, William J Cooper
This study reports the impact of two reactive species, hydroxyl radical and singlet oxygen, on the photochemical degradation of three selected pharmaceutical compounds in natural and reconstituted solutions of Suwannee River water. Absolute bimolecular rate constants (M(-1)s(-1)) were determined for the reaction of hydroxyl radical and singlet oxygen with danofloxacin ((6.15±0.11)×10(9); (7.50±0.13)×10(4)), fluvastatin ((6.96±0.16)×10(9); (1.64±0.18)×10(8)), and paroxetine ((8.65±0.12)×10(9), (1.18±0...
December 20, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/28005438/interactions-of-crizotinib-and-gefitinib-with-organic-anion-transporting-polypeptides-oatp-1b1-oatp1b3-and-oatp2b1-gefitinib-shows-contradictory-interaction-with-oatp1b3
#6
Toshihiro Sato, Hajime Ito, Ayaka Hirata, Takaaki Abe, Nariyasu Mano, Hiroaki Yamaguchi
1. The drug-drug interaction (DDI) mediated by organic anion-transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1 has a major impact on the hepatic clearance of drugs. The effects of tyrosine kinase inhibitors (TKIs) on OATPs have not been well studied. In the present study, we evaluated the contribution of OATPs to the hepatic uptake of crizotinib and gefitinib and the interaction of those TKIs with OATPs to estimate DDIs. 2. To clarify whether crizotinib and gefitinib were substrates for OATPs, we performed uptake studies...
December 22, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27989745/interaction-of-different-statins-with-model-membranes-by-nmr-data
#7
L F Galiullina, O V Aganova, I A Latfullin, G S Musabirova, A V Aganov, V V Klochkov
Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins reduce the amount of low-density lipoprotein (LDL) cholesterol, which is known as a well-established risk factor for atherosclerosis. Despite the fact that statins have a common pharmacologic target essential to sterol biosynthesis, their efficacy, safety, and potential non-LDL actions vary significantly for different statins. There is a hypothesis that pharmacological features of statins depend on their location in cell membrane, but to the present day there is a lack of information in literature on interactions of statins with the surface of the cell membrane in liquid media...
December 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27924788/effect-of-statins-type-on-incident-prostate-cancer-risk-a-meta-analysis-and-systematic-review
#8
Ping Tan, Chen Zhang, Shi-You Wei, Zhuang Tang, Liang Gao, Lu Yang, Qiang Wei
The aim of this study is to investigate the effect of statins type or even when grouping statins by hydrophilic or hydrophobic nature on prostate cancer risk. A literature search was performed without language restrictions using the databases of PubMed (1984.1-2015.3), MEDLINE (1984.1-2015.3), and EMBASE (1990.1-2015.3). Two independent reviewers appraised eligible studies and extracted data. Weighted averages were reported as relative risk (RR) with 95% confidence intervals (CI). Statistic heterogeneity scores were assessed with the standard Cochran's Q-test and I2 statistic...
December 2, 2016: Asian Journal of Andrology
https://www.readbyqxmd.com/read/27888640/chronotherapy-versus-conventional-statins-therapy-for-the-treatment-of-hyperlipidaemia
#9
REVIEW
Jose Manuel Izquierdo-Palomares, Jesus Maria Fernandez-Tabera, Maria N Plana, Almudena Añino Alba, Pablo Gómez Álvarez, Inmaculada Fernandez-Esteban, Luis Carlos Saiz, Pilar Martin-Carrillo, Óscar Pinar López
BACKGROUND: Elevated levels of total cholesterol and low-density lipoprotein play an important role in the development of atheromas and, therefore, in cardiovascular diseases. Cholesterol biosynthesis follows a circadian rhythm and is principally produced at night (between 12:00 am and 6:00 am). The adjustment of hypolipaemic therapy to biologic rhythms is known as chronotherapy. Chronotherapy is based on the idea that medication can have different effects depending on the hour at which it is taken...
26, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27884129/in-vivo-optical-coherence-tomography-visualization-of-intraplaque-neovascularization-at-the-site-of-coronary-vasospasm-a-case-report
#10
Kenichi Tsujita, Koichi Kaikita, Satoshi Araki, Toshihiro Yamada, Suguru Nagamatsu, Kenshi Yamanaga, Kenji Sakamoto, Sunao Kojima, Seiji Hokimoto, Hisao Ogawa
BACKGROUND: Coronary plaques in patients with coronary vasospastic angina have been characterized by diffuse intima-media thickening with homogeneous fibrous tissue, without confluent necrotic tissue. However, coronary vasospasm can trigger coronary thrombosis, and may play an important role in the pathogenesis of acute coronary syndromes, though the precise morphological mechanisms underlying this process remain unclear. CASE PRESENTATION: A 43-year-old man with a history of multivessel coronary vasospastic angina had been treated with long-acting diltiazem and fluvastatin since 2004...
November 25, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27861386/statins-and-risk-for-new-onset-diabetes-mellitus-a-real-world-cohort-study-using-a-clinical-research-database
#11
Dukyong Yoon, Seung Soo Sheen, Sukhyang Lee, Yong Jun Choi, Rae Woong Park, Hong-Seok Lim
Although concern regarding the increased risk for new-onset diabetes mellitus (NODM) after statin treatment has been raised, there has been a lack of evidence in real-world clinical practice, particularly in East Asians. We investigated whether statin use is associated with risk for NODM in Koreans. We conducted a retrospective cohort study using the clinical research database from electronic health records. The study cohort consisted of 8265 statin-exposed and 33,060 matched nonexposed patients between January 1996 and August 2013...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27858552/fluvastatin-inhibits-osteoclast-differentiation-and-p-gingivalis-lipopolysaccharide-induced-alveolar-bone-erosion-in-mice
#12
Nitin Kumar Pokhrel, Yong-Gun Kim, Jae-Young Kim, Hong-Hee Kim, Youngkyun Lee
BACKGROUND: Statins have been widely used to treat hypercholesterolemia. In addition to the inhibition of cholesterol synthesis, recent reports suggest bone anabolic property of statins. However, little notice has been paid to the direct effect of statins on osteoclastogenesis and bone resorption. METHODS: The effect of fluvastatin on osteoclast differentiation was determined using in vitro culture of mouse bone marrow macrophages (BMMs) in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL)...
November 18, 2016: Journal of Periodontology
https://www.readbyqxmd.com/read/27805296/the-sensitivity-of-head-and-neck-carcinoma-cells-to-statins-is-related-to-the-expression-of-their-ras-expression-status-and-statin-induced-apoptosis-is-mediated-via-suppression-of-the-ras-erk-and-ras-mtor-pathways
#13
Masanobu Tsubaki, Daichiro Fujiwara, Tomoya Takeda, Toshiki Kino, Yoshika Tomonari, Tatsuki Itoh, Motohiro Imano, Takao Satou, Katsuhiko Sakaguchi, Shozo Nishida
Statins induce apoptosis of tumor cells by inhibiting the prenylation of small G-proteins. However, the details of the apoptosis-inducing mechanisms remain poorly understood. The present study showed that the induction of apoptosis by statins in four different human head and neck squamous cell carcinoma (HNSCC) cell lines, HSC-3, HEp-2, Ca9-22, and SAS cells was mediated by increased caspase-3 activity. Statins induced apoptosis by the suppression of geranylgeranyl pyrophosphate biosynthesis. Furthermore, statins decreased the levels of phosphorylated ERK and mTOR by inhibiting the membrane localization of Ras and enhancing Bim expression in HSC-3 and HEp-2 cells...
November 2, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27766245/statins-increase-mitochondrial-and-peroxisomal-fatty-acid-oxidation-in-the-liver-and-prevent-non-alcoholic-steatohepatitis-in-mice
#14
Han-Sol Park, Jung Eun Jang, Myoung Seok Ko, Sung Hoon Woo, Bum Joong Kim, Hyun Sik Kim, Hye Sun Park, In-Sun Park, Eun Hee Koh, Ki-Up Lee
BACKGROUND: Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown...
October 2016: Diabetes & Metabolism Journal
https://www.readbyqxmd.com/read/27764723/efficacy-and-safety-of-long-term-treatment-with-statins-for-coronary-heart-disease-a-bayesian-network-meta-analysis
#15
Yongbin Lu, Zhiyuan Cheng, Yaxue Zhao, Xiaoyu Chang, Cynthia Chan, Yana Bai, Ning Cheng
BACKGROUND AND AIMS: Our study aims to evaluate the efficacy and safety of long-term treatment of statins for coronary heart disease (CHD). METHODS: Efficacy outcomes included changes in blood lipids, risk of CHD mortality and all-cause mortality. Safety outcomes were evaluated by the risk of adverse events (AE). Bayesian network meta-analysis was used to compare the direct and indirect effects between different statins. RESULTS: The systematic review showed that levels of blood lipids decreased during statin treatment...
November 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27754222/os-32-07-levorotatory-amlodipine-plus-fluvastatin-confer-additive-effects-on-retarding-endothelium-mesenchymal-transition-through-suppressing-rock1-expression
#16
Anping Cai, Yingqing Feng, Yingling Zhou, Jiyan Chen
OBJECTIVE: To investigate the effects and mechanisms of levorotatory (L)-amlodipine combined fluvastatin treatment on endothelium-mesenchymal transition (EndMT), a process related to hypertension development. DESIGN AND METHOD: Human umbilical vein endothelial cells (HUVECs) were used and divided to six groups based on different therapeutic strategies as follows: Blank Control, angiotensin-II (Ang-II), Ang-II+ rho-associated kinase (ROCK) inhibitor, Ang-II+ L-amlodipine, Ang-II+ fluvastatin, and Ang-II +L-amlodipine + fluvastatin groups...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27750346/-medication-management-simvastatin-and-amlodipin-a-clinically-relevant-drug-interaction
#17
Jane Schröder, Lisa Goltz, Holger Knoth
The clinical relevance of the drug-drug interaction simvastatin and amlodipine is appraised controversially by german simvastatin Summary of Product Characteristics (SPCs) and different drug interaction databases. Results of clinical trials have shown that simultaneous administration of simvastatin and amlodipine can increase simvastatin bioavailability. However, it is unclear whether this increase is associated with a higher risk for adverse drug events. So far there is no evidence that the combination might increase cases of myopathy or rhabdomyolysis...
October 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27734263/statin-attenuates-cell-proliferative-ability-via-taz-wwtr1-in-hepatocellular-carcinoma
#18
Takaaki Higashi, Hiromitsu Hayashi, Yuki Kitano, Kensuke Yamamura, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Shigeki Nakagawa, Hirohisa Okabe, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba
Diabetes and obesity are associated with non-alcoholic steatohepatitis and an increased incidence of hepatocellular carcinoma (HCC). TAZ and YAP are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. Statins are commonly used to patients with metabolic problems as hypercholesterolemia. Statins also have anti-cancer properties, and the cross-talk between mevalonate pathway and Hippo pathway was known. The aim of this study is to confirm the statin's anti-cancer effects on HCC cells and its survival benefits in HCC patients with curative surgery...
November 2016: Medical Oncology
https://www.readbyqxmd.com/read/27698930/statins-dose-dependently-exert-significant-chemopreventive-effects-against-various-cancers-in-chronic-obstructive-pulmonary-disease-patients-a-population-based-cohort-study
#19
Chun-Chao Chen, Yi-Ping Hsu, Ju-Chi Liu, Pai-Feng Kao, Li-Chin Sung, Chao-Feng Lin, Wen-Rui Hao, Shing-Hwa Liu, Szu-Yuan Wu
PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with an increased cancer risk. We evaluated the chemopreventive effect of statins against all cancers in COPD patients and identified the statin with the strongest chemopreventive effect. PATIENTS AND METHODS: All patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) from January 1, 2001, to December 31, 2012, were recruited. Each patient was followed to assess the following protective and risk factors for all cancers: age; sex; comorbidities (diabetes, hypertension, dyslipidemia) and the Charlson comorbidity index [CCI]); urbanization level; monthly income; and nonstatin drug use...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27649899/current-statins-show-calcium-channel-blocking-activity-through-voltage-gated-channels
#20
Niaz Ali, Robina Begum, Muhammad Saleh Faisal, Aslam Khan, Muhammad Nabi, Gulfam Shehzadi, Shakir Ullah, Waqar Ali
BACKGROUND: Statins are used for treatment of hypercholestremia. Common adverse reports associated with use of statins are generalized bodyache, rhabdomyolysis, muscles weakness and gastrointestinal disorders. The current work is an attempt to explain how smooth muscles of gastrointestinal tissues are affected by the current statins (Simvastatin, atorvastatin, fluvastatin and rosuvastatin). METHODS: Effects of the current statins were studied on spontaneous activity of isolated rabbits' jejunal preparations...
2016: BMC Pharmacology & Toxicology
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