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https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#1
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449329/impact-of-apolipoprotein-a-isoform-size-on-lipoprotein-a-lowering-in-the-hps2-thrive-study
#2
Sarah Parish, Jemma C Hopewell, Michael R Hill, Santica Marcovina, Elsa Valdes-Marquez, Richard Haynes, Alison Offer, Terje R Pedersen, Colin Baigent, Rory Collins, Martin Landray, Jane Armitage
BACKGROUND: Genetic studies have shown lipoprotein(a) (Lp[a]) to be an important causal risk factor for coronary disease. Apolipoprotein(a) isoform size is the chief determinant of Lp(a) levels, but its impact on the benefits of therapies that lower Lp(a) remains unclear. METHODS: HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is a randomized trial of niacin-laropiprant versus placebo on a background of simvastatin therapy...
February 2018: Circ Genom Precis Med
https://www.readbyqxmd.com/read/29447825/profilactic-role-of-simvastatin-and-mitomycin-c-in-tracheal-stenosis-after-tracheal-damage-study-in-rats
#3
Adnan Ekinci, Sema Koc, Ahmet Serhat Erdoğan, Hakan Kesici
OBJECTIVES: We aimed to investigate the prophylactic effect simvastatin of and mitomycin C (MMC) on laryngeal and tracheal stenosis in tracheotomised rats by histopathological evaluation of laryngotracheal segment. Randomized prospective single-blind. MATERIAL AND METHOD: Standard vertical tracheotomy was performed on 24 rats. Then the animals were randomly divided into three groups as A, B and C. In group A 0.4 mg/day once daily mitomycin C was injected to the paratracheal region for 14 days...
February 2018: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/29447225/low-apolipoprotein-a-i-levels-in-friedreich-s-ataxia-and-in-frataxin-deficient-cells-implications-for-therapy
#4
QingQing Wang, Lili Guo, Cassandra J Strawser, Lauren A Hauser, Wei-Ting Hwang, Nathaniel W Snyder, David R Lynch, Clementina Mesaros, Ian A Blair
Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disorder, which results primarily from reduced expression of the mitochondrial protein frataxin. FA has an estimated prevalence of one in 50,000 in the population, making it the most common hereditary ataxia. Paradoxically, mortality arises most frequently from cardiomyopathy and cardiac failure rather than from neurological effects. Decreased high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-l) levels in the general population are associated with an increased risk of mortality from cardiomyopathy and heart failure...
2018: PloS One
https://www.readbyqxmd.com/read/29444682/serum-igg-subclass-levels-and-risk-of-exacerbations-and-hospitalizations-in-patients-with-copd
#5
Fernando Sergio Leitao Filho, Seung Won Ra, Andre Mattman, Robert S Schellenberg, Gerard J Criner, Prescott G Woodruff, Stephen C Lazarus, Richard Albert, John E Connett, Meilan K Han, Fernando J Martinez, Janice M Leung, S F Paul Man, Shawn D Aaron, Robert M Reed, Don D Sin
BACKGROUND: The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. METHODS: We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653)...
February 14, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29442055/incidence-of-statin-drug-interactions-in-croatian-community-pharmacy
#6
I Samardzic, I Benkovic, V Bacic Vrca
Statins are among the most frequently issued drugs that patients usually need to take for a lifetime. They are often an integral part of a polytherapeutic approach in preventing and treating cardiovascular diseases. As such, they might often interact with drugs prescribed for treating acute and chronic conditions. A pharmacist is the final professional control before a drug reaches the patient and his role in preventing drug-drug interactions is crucial. The objective of this research was to analyse the incidence and relevance of potential drug interactions with statins in community pharmacy...
March 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29436616/synergistic-promoting-effects-of-pentoxifylline-and-simvastatin-on-the-apoptosis-of-triple-negative-mda-mb-231-breast-cancer-cells
#7
Yessica Cristina Castellanos-Esparza, Shuang Wu, Limin Huang, Catherine Buquet, Rong Shen, Berenice Sanchez-Gonzalez, Ethel Awilda García Latorre, Olivier Boyer, Remi Varin, Luis Antonio Jiménez-Zamudio, Anne Janin, Jean-Pierre Vannier, Hong Li, He Lu
Pentoxifylline (PTX), a xanthine family molecule and simvastatin (SIM), an anti-hypercholesterolemic agent, have recently been considered as sensitizers to chemotherapy and radiotherapy. The present in vitro study evaluated their antitumor synergistic effects on MDA‑MB‑231 breast cancer cells characterized by the triple‑negative phenotype (TNP). The anti-proliferative effects of these two agents were evaluated by MTT and clonogenic assays. Cell cycle progression was examined using propidium iodide staining...
February 9, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29436584/mitochondrial-protective-mechanism-of-simvastatin-protects-against-amyloid%C3%A2-%C3%AE-peptide-induced-injury-in-sh-sy5y-cells
#8
Yunzi Li, Qian Liu, Jing Sun, Jin Wang, Xinfeng Liu, Jing Gao
Mitochondrial dysfunction is implicated in the pathology of neuronal damage during Alzheimer's disease (AD). Previous studies suggest that simvastatin (SV) ameliorates amyloid β (Aβ)‑mediated cognitive impairment in AD patients and transgenic mice; however, the mechanisms remain unknown. To investigate the potential mechanisms by which SV protects against AD neurotoxicity, the present study used a series of cellular and molecular assays to analyze the effects of SV in an in vitro model of Aβ1‑42-induced injury...
February 5, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29435052/simvastatin-in-combination-with-meclofenamic-acid-inhibits-the-proliferation-and-migration-of-human-prostate-cancer-pc-3-cells-via-an-akr1c3-mechanism
#9
Yoshitaka Sekine, Hiroshi Nakayama, Yoshiyuki Miyazawa, Haruo Kato, Yosuke Furuya, Seiji Arai, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuto Ito, Kazuhiro Suzuki
Statins have become of interest in research due to their anticancer effects. However, the exact mechanism of their anticancer properties remains unclear. The authors previously reported that statins decrease intracellular cholesterol levels in androgen-independent prostate cancer cells. In de novo androgen synthesis, cholesterol is the primary material and certain enzymes have important roles. The present study aimed to determine whether simvastatin alters the expression of androgen synthesis-associated enzymes in androgen-independent prostate cancer cells...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434788/combined-treatment-with-simvastatin-and-rapamycin-attenuates-cardiac-allograft-rejection-through-the-regulation-of-t-helper-17-and-regulatory-t-cells
#10
Yingjie Liu, Lu Sun, Wei Chen, Junbo Chuai, Yu Shang, Dongyang Zhang, Bicheng Fu, Hai Tian, Shulin Jiang
Allograft rejection is an important issue post cardiac transplantation. In order to investigate the effect of combined treatment with simvastatin and rapamycin on allograft rejection, a cardiac transplantation rat model was employed in the present study. The survival time of rats following cardiac transplantation was recorded, while histopathological alterations were assessed by hematoxylin and eosin staining. The levels of transcription factors were measured by reverse transcription-quantitative polymerase chain reaction...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434767/simvastatin-inhibits-the-apoptosis-of-hippocampal-cells-in-a-mouse-model-of-alzheimer-s-disease
#11
Xiaoqin Hu, Chengwei Song, Ming Fang, Chengyan Li
Alzheimer's disease is associated with cognitive impairments that affect memory and executive functions. Simvastatin is a cholesterol-lowering statin drug that is used to control levels of cholesterol in the blood, particularly in cases of hypercholesterolemia, and may be used in the treatment of aneurysmal subarachnoid hemorrhage. Previous results have indicated that the apoptosis of hippocampal cells may serve a critical role in the progression of Alzheimer's disease. In the present study, it was determined whether Simvastatin inhibited the apoptosis of hippocampal cells in vitro and in vivo ...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29429367/obestatin-protects-and-reverses-nonalcoholic-fatty-liver-disease-and-its-associated-insulin-resistance-in-rats-via-inhibition-of-food-intake-enhancing-hepatic-adiponectin-signaling-and-blocking-ghrelin-acylation
#12
Eman F Khaleel, Ghada A Abdel-Aleem
This study investigated the ameliorative and protective effects of long-term obestatin administration (80 nmol/kg/ intraperitoneal injection (i.p.)) on the pathogenesis of high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) in rats. Rats (n = 8/group) were divided as control, NAFLD, NAFLD + Simvastatin, NAFLD + obestatin, NAFLD then obestatin, and obestatin then NAFLD. Obestatin co -or post-therapy significantly reduced hepatomegaly and reversed hyperlipidemia, hepatic lipid accumulation, and insulin resistance (IR)...
February 10, 2018: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29428718/synergistic-effects-of-simvastatin-and-bone-marrow-derived-mesenchymal-stem-cells-on-hepatic-fibrosis
#13
Yoon Ok Jang, Sung Hoon Kim, Mee-Yon Cho, Kyung Sik Kim, Kyu-Sang Park, Seung-Kuy Cha, Moon Young Kim, Sei Jin Chang, Soon Koo Baik
The beneficial effects of simvastatin on fibrosis in various organs have been reported. In addition, bone marrow (BM)-derived mesenchymal stem cells (MSCs) have been suggested as an effective therapy for hepatic fibrosis and cirrhosis. Recent evidence suggests that pharmacological treatment devoted to regulating stem cell function is a potential new therapeutic strategy that is drawing nearer to clinical practice. The aim of this study was to determine whether the combination treatment of simvastatin plus MSCs (Sim-MSCs) could have a synergistic effect on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model and hepatic stellate cells (HSCs)...
February 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29427912/adjunctive-therapy-with-statins-in-schizophrenia-patients-a-meta-analysis-and-implications
#14
Hong Shen, Rui Li, Rong Yan, Xia Zhou, Xia Feng, Mengjie Zhao, Hong Xiao
There are some conflicting results regarding the benefit of adjunctive therapy with statins for severity of negative symptoms in schizophrenia. This study aimed to verify whether statins use for adjunctive therapy was indeed beneficial to improve psychiatric symptoms in schizophrenia. The data were from CENTRAL, PubMed, Embase and MEDLINE. The Boolean search term used for the electronic database search was (statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR mevastatin OR pitavastatin OR pravastatin OR rosuvastatin OR cerivastatin) and (schizophrenia OR schizoaffective disorder OR psychosis)...
February 5, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29427701/statins-differentially-modulate-micrornas-expression-in-peripheral-cells-of-hyperlipidemic-subjects-a-pilot-study
#15
Tomás Zambrano, Rosario D C Hirata, Mario H Hirata, Álvaro Cerda, Luis A Salazar
AIM: Although statins are considered a cornerstone for the treatment of high cholesterol levels due to their powerful cholesterol-lowering effects, response to drug administration is still one of the main pitfalls of statin treatment. So far, the reasons underlying this undesired outcome are still poorly understood, but recently, various studies have suggested that miRNAs may be involved. Therefore, we aimed at evaluating the effect of short-term low-dose treatment with 2 statins on miRNAs expression in patients with hypercholesterolemia...
February 7, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29427042/amyotrophic-lateral-sclerosis-associated-with-statin-use-a-disproportionality-analysis-of-the-fda-s-adverse-event-reporting-system
#16
Beatrice A Golomb, Abril Verden, Alexis K Messner, Hayley J Koslik, Keith B Hoffman
INTRODUCTION: Apparent elevations in reporting of amyotrophic lateral sclerosis (ALS)-like conditions associated with statin use have been previously described from data obtained via US and European databases. OBJECTIVE: The aim of this study was to examine US FDA Adverse Event Reporting System (FAERS) data to compare reporting odds ratios (RORs) of ALS and ALS-like conditions between statins and other drugs, for each statin agent. METHODS: We assessed for disproportional rates of reported ALS and ALS-related conditions for each statin agent separately by using the ROR formula...
February 9, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29425980/dose-dependent-effects-of-statins-for-patients-with-aneurysmal-subarachnoid-hemorrhage-meta-regression-analysis
#17
REVIEW
Minh-Son To, Shivesh Prakash, Santosh I Poonnoose, Shailesh Bihari
OBJECTIVE: The study utilizes meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DINDs) and mortality in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Prospective, retrospective observational studies and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo)...
February 6, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29421861/simvastatin-protects-against-acetaminophen-induced-liver-injury-in-mice
#18
Huan Liang, Yang Feng, Ruixia Cui, Minglong Qiu, Jingyao Zhang, Chang Liu
The present study aimed to investigate the effect of simvastatin on acetaminophen (APAP) hepatotoxicity in a mouse model. Male C57BL/6 mice were allocated into the following groups: control, APAP, APAP+SIM10, APAP+SIM20, APAP+SIM100 and APAP+SIM200 groups. The mice in the APAP group were treated with saline intraperitoneally (i.p.) 72 h before and 24 h or 72 h after APAP challenge (i.p., 400 mg/kg of APAP). The simvastatin-treated groups were treated with different doses of simvastatin i.p. (10, 20, 100 and 200 mg/kg/day) as in the APAP group...
February 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29416709/low-dose-statin-treatment-increases-prostate-cancer-aggressiveness
#19
Alfredo Caro-Maldonado, Laura Camacho, Amaia Zabala-Letona, Verónica Torrano, Sonia Fernández-Ruiz, Kepa Zamacola-Bascaran, Leire Arreal, Lorea Valcárcel-Jiménez, Natalia Martín-Martín, Juana M Flores, Ana R Cortazar, Patricia Zúñiga-García, Amaia Arruabarrena-Aristorena, Fabienne Guillaumond, Diana Cabrera, Juan M Falcón-Perez, Ana M Aransay, Antonio Gomez-Muñoz, Mireia Olivan, Juan Morote, Arkaitz Carracedo
Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that in vivo simvastatin administration alone increases prostate cancer aggressiveness...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29414865/development-of-an-effective-6-methylpurine-counterselection-marker-for-genetic-manipulation-in-thermococcus-barophilus
#20
Tiphaine Birien, Axel Thiel, Ghislaine Henneke, Didier Flament, Yann Moalic, Mohamed Jebbar
A gene disruption system for Thermococcus barophilus was developed using simvastatin (HMG-CoA reductase encoding gene) for positive selection and 5-Fluoroorotic acid (5-FOA), a pyrF gene for negative selection. Multiple gene mutants were constructed with this system, which offers the possibility of complementation in trans, but produces many false positives (<80%). To significantly reduce the rate of false positives, we used another counterselective marker, 6-methylpurine (6-MP), a toxic analog of adenine developed in Thermococcus kodakarensis, consistently correlated with the TK0664 gene (encoding a hypoxanthine-guanine phosphoribosyl-transferase)...
February 7, 2018: Genes
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