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https://www.readbyqxmd.com/read/28226198/olanzapine-induced-early-cardiovascular-effects-are-mediated-by-the-biological-clock-and-prevented-by-melatonin
#1
Francisco Romo-Nava, Frederik N Buijs, Marcela Valdés-Tovar, Gloria Benítez-King, MariCarmen Basualdo, Mercedes Perusquía, Gerhard Heinze, Carolina Escobar, Ruud M Buijs
Second generation antipsychotics (SGA) are associated with adverse cardiometabolic side-effects contributing to premature mortality in patients. While mechanisms mediating these cardiometabolic side-effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in SGA-treated patients. Since one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus (SCN), we hypothesized that the SCN is involved in SGA-induced early cardiovascular effects in Wistar rats...
February 22, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28225806/capsaicin-reduces-alzheimer-associated-tau-changes-in-the-hippocampus-of-type-2-diabetes-rats
#2
Weijie Xu, Juanhong Liu, Delin Ma, Gang Yuan, Yan Lu, Yan Yang
Type 2 diabetes (T2D) is a high-risk factor for Alzheimer's disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight...
2017: PloS One
https://www.readbyqxmd.com/read/28223222/disrupting-the-key-circadian-regulator-clock-leads-to-age-dependent-cardiovascular-disease
#3
Faisal J Alibhai, Jonathan LaMarre, Cristine J Reitz, Elena V Tsimakouridze, Jeffrey T Kroetsch, Steffen-Sebastian Bolz, Alex Shulman, Samantha Steinberg, Thomas P Burris, Gavin Y Oudit, Tami A Martino
The circadian mechanism underlies daily rhythms in cardiovascular physiology and rhythm disruption is a major risk factor for heart disease and worse outcomes. However, the role of circadian rhythms is generally clinically unappreciated. Clock is a core component of the circadian mechanism and here we examine the role of Clock as a vital determinant of cardiac physiology and pathophysiology in aging. Clock(Δ19/Δ19) mice develop age-dependent increases in heart weight, hypertrophy, dilation, impaired contractility, and reduced myogenic responsiveness...
February 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28223128/a-screening-assay-for-the-identification-of-host-cell-requirements-and-antiviral-targets-for-hepatitis-d-virus-infection
#4
Bettina Buchmann, Katinka Döhner, Thomas Schirdewahn, Beate Sodeik, Michael P Manns, Heiner Wedemeyer, Sandra Ciesek, Thomas von Hahn
Hepatitis delta virus (HDV) is a minimalistic satellite virus of hepatitis B virus (HBV). HBV/HDV co-infection, i.e. "hepatitis D", is the most severe form of viral hepatitis. No effective therapy for HDV infection is available partly due to the fact that HDV is a highly host-dependent virus devoid of any potentially drugable enzyme encoded in its small genome. In this study we present a semi-automated method to evaluate HDV infection and replication under the influence of different drugs. We utilized a Huh-7/hNTCP cell culture based system in a 96-well plate format, an automated microscope and image acquisition as well as analysis with the CellProfiler software to quantify the impact of these drugs on HDV infection...
February 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28220212/rho-kinase-inhibition-ameliorates-cyclophosphamide-induced-cystitis-in-rats
#5
Andrzej Wróbel, Urszula Doboszewska, Ewa Rechberger, Karol Rojek, Anna Serefko, Ewa Poleszak, Krystyna Skalicka-Woźniak, Jarosław Dudka, Piotr Wlaź
Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CYP). Studies have indicated that Rho kinase (ROCK) inhibitors may suppress detrusor overactivity symptoms and possess anti-inflammatory properties. The aim of the present study was to investigate whether inhibition of ROCK reduces cystometric and histopathological changes associated with CYP-induced cystitis. The rats received GSK 269962, a ROCK inhibitor, at a dose of 30 mg/kg daily, or vehicle for 7 days. Then, acute chemical cystitis leading to bladder overactivity was induced by CYP injection (200 mg/kg i...
February 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28216152/1-25-dihydroxyvitamin-d3-prevents-the-development-of-diabetic-cardiomyopathy-in-type-1-diabetic-rats-by-enhancing-autophagy-via-inhibiting-the-%C3%AE-catenin-tcf4-gsk-3%C3%AE-mtor-pathway
#6
Huili Wei, Hua Qu, Hang Wang, Baolan Ji, Yao Ding, Dan Liu, Yang Duan, Huimin Liang, Chuan Peng, Xiaoqiu Xiao, Huacong Deng
Diabetic cardiomyopathy (DCM) can increase the risk of heart failure and death in diabetic patients. However, no effective approaches are available to prevent its progression and development. Studies have shown that vitamin D is greatly implicated in cardiac hypertrophy and fibrosis, and there is a high prevalence of vitamin D deficiency in diabetic patients. In this study, we investigated whether 1,25-Dihydroxyvitamin-D3 (1,25D3) can improve DCM through a vitamin D receptor (VDR)-dependent mechanism associated with autophagy and the β-catenin/T-cell factor/lymphoid enhancer factor (TCF4)/glycogen synthase kinase-3β (GSK-3β)/mammalian target of rapamycin (mTOR) pathway...
February 16, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28215942/how-to-identify-and-eliminate-compounds-with-a-risk-of-high-clinical-dose-during-the-early-phase-of-lead-optimisation-in-drug-discovery
#7
Simon Teague, Klara Valko
An alternative approach has been developed to estimate the clinical dose of new drug molecules at an early stage in the drug discovery process. This approach has been compared to traditional methods using the clinical dose as indicated on the drug label of 136 marketed drugs. At the early stages of drug discovery only in silico predictions or some initial in vitro screening data are normally available, typically parameters such as affinity/potency (pXC50)from isolated enzymes or receptors, measured albumin and phospholipid binding using biomimetic HPLC measurements, and in vitro clearance using P450 enzymes or liver microsomes...
February 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28213107/hypoglycemic-effect-of-the-polyphenols-rich-extract-from-rose-rugosa-thunb-on-high-fat-diet-and-stz-induced-diabetic-rats
#8
Liu Liu, Dan Tang, Haiqing Zhao, Xuelei Xin, Haji Akber Aisa
ETHNOPHARMACOLOGICAL RELEVANCE: Rosa rugosa Thunb is traditional Uygur medicine, it is widely used for regulating blood condition, nourishing liver and gallbladder in Uygur ancient prescription. But the mechanism of Rosa rugosa Thunb on diabetes is still unclear. In here, we studied the hypoglycemic effect and explained one probable pathway of polyphenols rich extract from Rosa rugosa Thunb (RPE) on diabetic rats. MATERIALS AND METHODS: In vitro, the effect of RPE on α-glucosidase inhibition was finished, and the antioxidant activity of RPE was evaluated by ABTS and DPPH assay...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28211103/impaired-learning-and-memory-in-rats-induced-by-a-high-fat-diet-involvement-with-the-imbalance-of-nesfatin-1-abundance-and-copine-6-expression
#9
Zheng Chen, Ya-Yun Xu, Rui Wu, Yin-Xiu Han, Yue Yu, Jin-Fang Ge, Fei-Hu Chen
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, resulting not only in liver dysfunction, glucose and lipid metabolism disorder, but also in neuropsychiatric damage. In the present study, a NAFLD rat model was established via feeding of a high-fat diet, and the behavior was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST), and the Morris water maze (MWM). The plasma concentrations of alanine aminotransferase (ALT), glucose, free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique...
February 17, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28208230/emerging-role-of-gsk-3%C3%AE-in-the-pathobiology-of-classical-hodgkin-lymphoma
#10
Claudio Agostinelli, Silvia Carloni, Francesco Limarzi, Simona Righi, Maria Antonella Laginestra, Gerardo Musuraca, Michelangelo Fiorentino, Roberta Napolitano, Antonio Cuneo, Daniele Vergara, Pier Luigi Zinzani, Sabattini Elena, Stefano A Pileri, Serena De Matteis
AIMS: GSK-3β is a serine/threonine kinase involved in glycogen metabolism, cell cycle progression, differentiation, embryogenesis, migration, metabolism, survival and cellular senescence. Its main biological function is to inhibit β-catenin by sequestration and promotion of its proteasomal degradation in the Wnt canonical pathway, however GSK-3β interacts with multiple signaling pathways and aberrant expression of the enzyme was reported in many solid neoplasms. This study aimed to investigate the biological relevance of GSK-3β in classical Hodgkin Lymphomas (cHL)...
February 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28207769/role-of-glycogen-synthase-kinase-3%C3%AE-and-ppar-%C3%AE-on-epithelial-to-mesenchymal-transition-in-dss-induced-colorectal-fibrosis
#11
Jacopo Di Gregorio, Roberta Sferra, Silvia Speca, Antonella Vetuschi, Caroline Dubuquoy, Pierre Desreumaux, Simona Pompili, Loredana Cristiano, Eugenio Gaudio, Vincenzo Flati, Giovanni Latella
BACKGROUND: Intestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT). AIM: To evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28205608/blockage-of-transient-receptor-potential-vanilloid-4-alleviates-myocardial-ischemia-reperfusion-injury-in-mice
#12
Qian Dong, Jing Li, Qiong-Feng Wu, Ning Zhao, Cheng Qian, Dan Ding, Bin-Bin Wang, Lei Chen, Ke-Fang Guo, Dehao Fu, Bing Han, Yu-Hua Liao, Yi-Mei Du
Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24-72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199981/growth-differentiation-factor-15-induces-growth-and-metastasis-of-human-liver-cancer-stem-like-cells-via-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling
#13
Qiong Xu, Hai-Xu Xu, Jin-Ping Li, Song Wang, Zheng Fu, Jing Jia, Li Wang, Zhi-Feng Zhu, Rong Lu, Zhi Yao
: Cancer stem cells in liver cancer are thought to be responsible for tumor recurrence and metastasis. However, the factors that mediate this mechanism have yet to be completely elucidated. In this study, we isolated CD13+CD44+ sphere cells (SCs) derived from liver cancer tissues and SK-Hep-1 cells, which possessed cancer stem cell-like properties. Through cytokine array analysis, growth differentiation factor 15 (GDF15) was significantly increased in SCs. Clinical data showed GDF15 was overexpressed in liver cancer tissues and was positively related to pathological grading...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197936/salvianolic-acid-a-protects-neonatal-cardiomyocytes-against-hypoxia-reoxygenation-induced-injury-by-preserving-mitochondrial-function-and-activating-akt-gsk-3%C3%AE-signals
#14
Xue-Li Li, Ji-Ping Fan, Jian-Xun Liu, Li-Na Liang
OBJECTIVE: To investigate the effects of salvianolic acid A (SAA) on cardiomyocyte apoptosis and mitochondrial dysfunction in response to hypoxia/reoxygenation (H/R) injury and to determine whether the Akt signaling pathway might play a role. METHODS: An in vitro model of H/R injury was used to study outcomes on primary cultured neonatal rat cardiomyocytes. The cardiomyocytes were treated with 12.5, 25, 50 μg/mL SAA at the beginning of hypoxia and reoxygenation, respectively...
February 15, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28197626/kdm6a-and-kdm6b-altered-expression-in-malignant-pleural-mesothelioma
#15
Sian Cregan, Maeve Breslin, Gerard Roche, Sigrid Wennstedt, Lauren MacDonagh, Cinaria Albadri, Yun Gao, Kenneth J O'Byrne, Sinead Cuffe, Stephen P Finn, Steven G Gray
Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197192/subhypnotic-doses-of-propofol-impair-spatial-memory-retrieval-in-rats
#16
Hu Liu, Ting Wang, Wei Dai, Zheng Jiang, Yuan-Hai Li, Xue-Sheng Liu
Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β (GSK-3β) activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28196122/detrimental-elavl-1-hur-dependent-gsk3%C3%AE-mrna-stabilization-impairs-resolution-in-acute-respiratory-distress-syndrome
#17
Olivia Hoffman, Nana Burns, István Vadász, Holger K Eltzschig, Michael G Edwards, Christine U Vohwinkel
A hallmark of acute respiratory distress syndrome (ARDS) is accumulation of protein-rich edema in the distal airspaces and its removal is critical for patient survival. Previous studies have shown a detrimental role of Glycogen Synthase Kinase (GSK) 3β during ARDS via inhibition of alveolar epithelial protein transport. We hypothesized that post-transcriptional regulation of GSK3β could play a functional role in ARDS resolution. To address this hypothesis, we performed an in silico analysis to identify regulatory genes whose expression correlation to GSK3β messenger RNA utilizing two lung cancer cell line array datasets...
2017: PloS One
https://www.readbyqxmd.com/read/28195036/gsk-3%C3%AE-inhibition-induced-neuroprotection-regeneration-and-functional-recovery-after-intracerebral-hemorrhagic-stroke
#18
Yingying Zhao, Zheng Zachory Wei, James Ya Zhang, Yongbo Zhang, Soonmi Won, Jinmei Sun, Shan Ping Yu, Jimei Li, Ling Wei
Hemorrhagic stroke is a devastating disease that lacks effective therapies. In the present investigation, we tested 6-bromoindirubin-3'-oxime (BIO) as a selective glycogen synthase kinase-3β (GSK-3β) inhibitor in a mouse model of intracerebral hemorrhage (ICH). ICH was induced by injection of collagenase IV into the striatum of 8 to 10-week old C57BL/6 mice. BIO (8 µg/kg, i.p.) was administered following either an acute delivery (0 - 2 hr delay) or a prolonged regimen (every 48 hrs starting at 3 days postICH)...
February 14, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28194557/-4z-15z-octadecadienoic-acid-inhibits-glycogen-synthase-kinase-3%C3%AE-and-glucose-production-in-h4iie-cells
#19
Jun Yoshida, Shota Uesugi, Tetsuaki Kawamura, Ken-Ichi Kimura, Dawei Hu, Shuang Xia, Naoki Toyooka, Masao Ohnishi, Hideki Kawashima
Many uncommon non-methylene-interrupted fatty acids (NMI FA) are present in limpet gonads, but their biological properties remain unknown. To investigate new biological effects of naturally occurring NMI FA in eukaryotic cells, the biological activities of structurally analogous (4Z,15Z)-octadecadienoic acid (1), (9Z,20Z)-tricosadienoic acid (2), and (12Z,23Z)-hexacosadienoic acid (3) were examined by using a yeast-based drug-screening system using the Ca(2+)-sensitive mutant strain, Saccharomyces cerevisiae (zds1Δ erg3Δ pdr1Δ pdr3Δ)...
February 13, 2017: Lipids
https://www.readbyqxmd.com/read/28186985/mir-124-3p-attenuates-hyperphosphorylation-of-tau-protein-induced-apoptosis-via-caveolin-1-pi3k-akt-gsk3%C3%AE-pathway-in-n2a-app695swe-cells
#20
Qingmei Kang, Yue Xiang, Dan Li, Jie Liang, Xiong Zhang, Fanlin Zhou, Mengyuan Qiao, Yingling Nie, Yurong He, Jingyi Cheng, Yubing Dai, Yu Li
Hyperphosphorylation of Tau forming neurofibrillary tangles has been considered as a crucial event in the pathogenesis of Alzheimer's disease (AD). MiR-124-3p belongs to microRNA (miRNA) family and was markedly decreased in AD, however, the functions of miR-124-3p in the pathogenesis of AD remain unknown. We observed that the expression of miR-124-3p was significantly decreased in N2a/APP695swe cells; and transfection of miR-124-3p mimics not only attenuated cell apoptosis and abnormal hyperphosphorylation of Tau protein without any changes of total Tau protein, but also increased expression levels of Caveolin-1, phosphoinositide 3-kinase (PI3K), phospho-Akt (Akt-Ser473)/Akt, phospho-glycogen synthase kinase-3 beta (GSK-3β-Ser9)/GSK-3β in N2a/APP695swe cells...
February 7, 2017: Oncotarget
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