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Yuefeng Zhang, Risheng Huang, Weihe Zhou, Qifeng Zhao, Zhenye Lü
Myocardial ischemia/reperfusion (I/R) injury is a leading cause of morbidity and mortality. In this study, we investigated the role of miR-192-5p in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis. H9c2 cardiomyocytes were subjected to H/R and tested for miR-192-5p expression. Overexpression and knockdown experiments were performed to determine the effects of manipulating miR-192-5p on apoptotic responses. H/R-treated H9c2 cells exhibited a 2.2-fold increase in miR-192-5p levels. Overexpression of miR-192-5p significantly augmented apoptosis in H9c2 cells after H/R, which was accompanied by a significant increase in the ratio of Bax/Bcl-2...
October 25, 2016: Journal of Biochemical and Molecular Toxicology
Mustafa Ceylan, Umit M Kocyigit, Necibe Canan Usta, Belma Gürbüzlü, Yusuf Temel, Saleh H Alwasel, İlhami Gülçin
Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti-HIV agents. In this study, the synthesis of novel tetralone-based benzothiazepine derivatives (1-16) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography from fresh human red blood cells...
October 25, 2016: Journal of Biochemical and Molecular Toxicology
Hui Zhao, Nainan Hei, Yiling Wu, Winston Chan, Xiudong Lei, Carrie Cameron, Shine Chang, Mariana Chavez-MacGregor, Sharon H Giordano
BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project B35 and International Breast Cancer Intervention Studies II Ductal Carcinoma In Situ trials showed similar treatment effects of anastrozole and tamoxifen in reducing cancer recurrence risk among ductal carcinoma in situ (DCIS) patients. Studies have shown low levels of hormone therapy drug initiation for DCIS patients, but the current body of literature lacks information on the 5-year adherence rates for these drugs from population-based studies...
October 25, 2016: Cancer
J H M Driessen, F de Vries, H van Onzenoort, N C Harvey, C Neef, J van den Bergh, P Vestergaard, R M A Henry
The aim of the present study was to estimate the effect of incretins on fracture risk in the real world situation by meta-analysis of the available population-based cohort data. Pubmed and Embase were searched for original articles investigating use of incretin agents, and fracture risk up to December 2015. Adjusted results were extracted and results were pooled by use of generic inverse variance methods, assuming a random-effects model. Neither current dipeptidyl peptidase 4 - inhibitors use, nor current glucagon-like peptide 1 receptor agonists use was associated with a decreased risk of fracture: pooled relative risk [pooled RR (95% CI): 1...
October 25, 2016: British Journal of Clinical Pharmacology
Cheng-Feng Chiang, Mike Flint, Jin-Mann S Lin, Christina F Spiropoulou
Andes virus (ANDV) is the major cause of hantavirus pulmonary syndrome (HPS) in South America. Despite a high fatality rate (up to 40%), no vaccines or antiviral therapies are approved to treat ANDV infection. To understand the role of endocytic pathways in ANDV infection, we used 3 complementary approaches to identify cellular factors required for ANDV entry into human lung microvascular endothelial cells. We screened an siRNA library targeting 140 genes involved in membrane trafficking, and identified 55 genes required for ANDV infection...
2016: PloS One
Mindi Zhao, Jianqiang Wu, Youhe Gao
Urine, reflecting many changes in the body, is a better source than blood for biomarker discovery. However, even under physiological conditions, the urine proteome often varies. Understanding how various regulating factors affect urine proteome helps link changes to urine proteome with urinary biomarkers of physiological conditions as well as corresponding diseases. To evaluate the possible impact of α1-adrenergic receptor on urine proteome, this study investigated effects of the specific inhibitor prazosin on the urine proteome in a rat model by using tandem mass tagging and two-dimensional liquid chromatography-tandem mass spectrometry...
2016: PloS One
Hui Ren, Nigel P Birch, Vinod Suresh
Robust and reproducible in vitro models are required for investigating the pathways involved in fluid homeostasis in the human alveolar epithelium. We performed functional and phenotypic characterisation of ion transport in the human pulmonary epithelial cell lines NCI-H441 and A549 to determine their similarity to primary human alveolar type II cells. NCI-H441 cells exhibited high expression of junctional proteins ZO-1, and E-cadherin, seal-forming claudin-3, -4, -5 and Na+-K+-ATPase while A549 cells exhibited high expression of pore-forming claudin-2...
2016: PloS One
Nawel Haïli, Julien Louap, Michel Canonge, Franjo Jagic, Christelle Louis-Mondésir, Thierry Chardot, Pierre Briozzo
The membrane proteins acyl-CoA:diacylglycerol acyltransferases (DGAT) are essential actors for triglycerides (TG) biosynthesis in eukaryotic organisms. Microbial production of TG is of interest for producing biofuel and value-added novel oils. In the oleaginous yeast Yarrowia lipolytica, Dga1p enzyme from the DGAT2 family plays a major role in TG biosynthesis. Producing recombinant DGAT enzymes pure and catalytically active is difficult, hampering their detailed functional characterization. In this report, we expressed in Escherichia coli and purified two soluble and active forms of Y...
2016: PloS One
Kuan-Ho Lin, Chien-Liang Liu, Wei-Wen Kuo, Catherine Reena Paul, Wei-Kung Chen, Su-Ying Wen, Cecilia Hsuan Day, Hsi-Chin Wu, Vijaya Padma Viswanadha, Chih-Yang Huang
Cardiac trauma has been recognized as a complication associated with blunt chest trauma involving coronary artery injury, myocardium contusion and myocardial rupture. Secondary cardiac injuries after trauma supposed to be a critical factor in trauma patients, but the mechanism is not fully explored. Overproduction of TNF-alpha had been reported in multiple trauma animals, this induces oxidative stress resulting in cardiac apoptosis. Apoptosis gradually increases after trauma and reaches to a maximum level in 12 h time...
2016: PloS One
Jay N Lozier, Mark T Kloos, Elizabeth P Merricks, Nathaly Lemoine, Margaret H Whitford, Robin A Raymer, Dwight A Bellinger, Timothy C Nichols
Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons...
2016: Comparative Medicine
James M Mutunga, Qiao-Hong Chen, Dawn M Wong, Polo C-H Lam, Jianyong Li, Maxim M Totrov, Aaron D Gross, Paul R Carlier, Jeffrey R Bloomquist
Widespread pyrethroid resistance has caused an urgent need to develop new insecticides for control of the malaria mosquito, Anopheles gambiae. Insecticide discovery efforts were directed towards the construction of bivalent inhibitors that occupy both the peripheral and catalytic sites of the mosquito acetylcholinesterase (AChE). It was hypothesized that this approach would yield a selective, high potency inhibitor that would also circumvent known catalytic site mutations (e.g. G119S) causing target site resistance...
October 2016: Chimia
Jeffery S Babischkin, Graham W Aberdeen, Gerald J Pepe, Eugene D Albrecht
We have shown that fetal adrenal fetal zone (FZ) volume and serum dehydroepiandrosterone sulfate (DHAS) levels were increased, whereas definitive and transitional zone (DZ/TZ) volume was unaltered, in baboons in which estrogen levels were suppressed by administration of the aromatase inhibitor letrozole. The interaction of the melanocortin 2 receptor (MC2R) with its accessory protein (MRAP) is essential for trafficking MC2R to the adrenal cell surface for binding to ACTH. The present study determined whether the estrogen-dependent regulation of fetal adrenocortical development is mediated by ACTH and/or expression/interaction of MC2R and MRAP...
October 25, 2016: Endocrinology
Ursula R Rodgers, Thomas Lanyon-Hogg, Naoko Masumoto, Markus Ritzefeld, Rosemary Burke, Julian Blagg, Anthony I Magee, Edward W Tate
The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, raising interest in Hhat as a novel drug target. A recently identified series of dihydrothienopyridines has been proposed to function via this mode of action; however, the lead compound in this series (RUSKI-43) was subsequently shown to possess cytotoxic activity unrelated to canonical Shh signaling...
October 25, 2016: ACS Chemical Biology
Ross S Firestone, Scott A Cameron, Peter C Tyler, Rodrigo Gay Ducati, Adam Z Spitz, Vern L Schramm
5'-Methylthioadenosine phosphorylase (MTAP) and 5'-methylthioadenosine nucleosidase (MTAN) catalyze the phosphorolysis and hydrolysis of 5'-methylthioadenosine (MTA), respectively. Both enzymes have low KM values for their substrates. Kinetic assays for these enzymes are challenging, as the ultraviolet absorbance spectra for reactant MTA and product adenine are similar. We report a new assay using 2-amino-5'-methylthioadenosine (2AMTA) as an alternative substrate for MTAP and MTAN enzymes. Hydrolysis or phosphorolysis of 2AMTA forms 2,6-diaminopurine, a fluorescent and easily quantitated product...
October 25, 2016: Analytical Chemistry
Trevor P E Williams, Scott Shaw, Adam Porter, Larry Berkwitt
OBJECTIVE: To review information regarding etiology, pathophysiology, and treatment options for aortic thrombotic disease in dogs. ETIOLOGY: Diseases resulting in hypercoagulable states can cause thrombus formation in the distal aorta, and account for the majority of cases of aortic thrombosis (ATh) in dogs, although a substantial number of cases have no identifiable underlying cause. Aortic thromboembolism (ATE) also occurs but appears to be much less frequently documented...
October 25, 2016: Journal of Veterinary Emergency and Critical Care
Hao Liu, Wei Ye, Hai-Feng Chen
Acetylcholinesterase is a potent enzyme that regulates neurotransmission by rapidly hydrolyzing the neurotransmitter acetylcholine in synapses of the nervous system. As drug target of anti-AD, it has catalytic and peripheral anionic sites. However, the regulation relation between these two sites is unclear. Therefore, we constructed dynamics fluctuation network based on all-atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in double site system (hAChE/TZ5) is distinctly different from that in the free state and single site systems (hAChE/huprine and hAChE/1YL)...
October 25, 2016: Chemical Biology & Drug Design
Yoshinori Imura, Takaaki Nakai, Shutaro Yamada, Hidetatsu Outani, Satoshi Takenaka, Kenichiro Hamada, Nobuhito Araki, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma with a poor prognosis and thus novel therapeutic strategies for SS are urgently required. In the present study, we investigated functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS. Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells...
October 24, 2016: Cancer Science
Wan-Ju Lee, Leslie Briars, Todd A Lee, Gregory S Calip, Katie J Suda, Glen T Schumock
OBJECTIVE: To characterize the use of tumor necrosis factor-alpha inhibitors (TNFI) in children with juvenile idiopathic arthritis (JIA) and young adults with rheumatoid arthritis (RA). METHODS: Patients with incident JIA or RA were identified using the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2013. The incident diagnosis was defined as no prior claims with a JIA/RA code and no JIA/RA medications recorded during the previous 6 months...
October 25, 2016: Pharmacotherapy
Arne Ring, Tom Morris, Marcin Wozniak, Nikol Sullo, William Dott, Veerle Verheyden, Tracy Kumar, Nigel Brunskill, Rakesh Vaja, Gavin J Murphy
BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cardiac surgery. There is no effective prevention or treatment. Sildenafil citrate (Revatio®, Pfizer Inc), a phosphodiesterase type 5 inhibitor, prevents post cardiac surgery AKI in pre-clinical studies, however its use is contraindicated in patients with symptomatic cardiovascular disease. METHODS: To assess the safety and pharmacokinetics of intravenous sildenafil in cardiac surgery patients we conducted an open label, dose escalation study with 6 patients per dose level...
October 25, 2016: British Journal of Clinical Pharmacology
François Seghers, Xavier Yerna, Nadège Zanou, Olivier Devuyst, Rudi Vennekens, Bernd Nilius, Philippe Gailly
The renin - angiotensin system is a crucial blood pressure regulation system. It consists of a hormonal cascade where the rate-limiting enzyme is renin, which is secreted in blood flow by renal juxtaglomerular (JG) cells in response to low pressure in the renal afferent arteriole. In contrast, an increase in blood pressure results in a decreased renin secretion. This is accompanied by a transitory increase in [Ca(2+) ]i of JG cells. The inverse relationship between [Ca(2+) ]i and renin secretion has been called the "calcium paradox" of renin release...
October 25, 2016: Journal of Physiology
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