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Clinical and Experimental Pharmacology & Physiology

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https://www.readbyqxmd.com/read/28741726/ns1643-enhances-ionic-currents-in-a-g604s-wt-herg-co-expression-system-associated-with-long-qt-syndrome-2
#1
JianHua Huo, Xueyan Guo, Qun Lu, Hua Qiang, Ping Liu, Ling Bai, Christopher L H Huang, Yanmin Zhang, Aiqun Ma
Loss of function mutations in the human ether-a-go-go-related gene (hERG) cause long QT syndrome type 2 (LQT2). Most LQT2 patients are heterozygous mutation carriers in which the mutant hERG exerts potent dominant-negative effects. 1, 3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) is known to enhance IKr in WT-hERG. We investigated its actions following lipofectamine-induced expression of both mutant G604S- and WT-hERG in the heterologous HEK293 expression system. Cells transfected with pcDNA3-G604S-hERG did not lead to any expression of detectable currents whether before or following NS1643 challenge...
July 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28732110/growth-inhibitory-effect-of-%C3%AE-eudesmol-on-cholangiocarcinoma-cells-and-its-potential-suppressive-effect-on-heme-oxygenase-1-production-stat1-3-activation-and-nf-%C3%AE%C2%BAb-downregulation
#2
Vivek Bhakta Mathema, Wanna Chaijaroenkul, Juntra Karbwang, Kesara Na-Bangchang
Cholangiocarcinoma (CCA) is a progressively fatal form of cancer originating from the malignant transformation of hepatic biliary cholangiocytes. The present study reports for the first time in vitro growth inhibitory activities of β-eudesmol, the bioactive sesquiterpenoid present in the rhizome of Atractylodes lancea (Thunb) DC., with respect to its underlying potential effects on heme oxygenase-1 (HO-1) production, STAT1/3 phosphorylation, and NF-κB protein expression in human CCA cell line CL-6. The cytotoxic effect of β-eudesmol on CL-6 cells was evaluated by MTT assay using normal human embryonic fibroblast (OUMS) as a control cell line...
July 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28732106/specific-%C3%AE-7-nicotinic-acetylcholine-receptor-agonist-ameliorates-isoproterenol-induced-cardiac-remodeling-in-mice-through-tgf-%C3%AE-1-smad3-pathway
#3
Yong-Hua Yang, Huan-Le Fang, Ming Zhao, Xiang-Lan Wei, Ning Zhang, Shun Wang, Yi Lu, Xiao-Jiang Yu, Lei Sun, Xi He, Dong-Ling Li, Jin-Jun Liu, Wei-Jin Zang
It is well-accepted that inflammation plays an important role in the development of cardiac remodeling and that therapeutic approaches targeting inflammation can inhibit cardiac remodeling. Although a large amount of evidence indicates that activation of α7 nicotinic acetylcholine receptor (α7nAChR) causes an anti-inflammatory effect, the role of α7nAChR in cardiac remodeling and the underlying mechanism have not been established. To investigate the effect of the specific α7nAChR agonist, PNU282987, on cardiac remodeling induced by isoproterenol (ISO 60 mg/kg/d) in mice, the cardiomyocyte cross-sectional area (CSA) and collagen volume fraction were evaluated by hematoxylin and eosin (HE) and Masson staining, respectively...
July 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28731589/effects-of-nitric-oxide-on-large-conductance-ca-2-activated-k-currents-in-human-cardiac-fibroblasts-through-pka-and-pkg-related-pathways
#4
Hyemi Bae, Inja Lim
The human cardiac fibroblast (HCF) is the most abundant cell type in the myocardium, and HCFs play critical roles in maintaining normal cardiac function. However, unlike cardiomyocytes, the electrophysiology of HCFs is not well established. In the cardiovascular system, Ca(2+) -activated K(+) (KCa) channels have distinct physiological and pathological functions, and nitric oxide (NO) play key roles. In this study, we investigated the potential effects of NO on KCa channels in HCFs. We recorded strong oscillating, well-maintained outward K(+) currents without marked inactivation throughout the test pulse period and detected outward rectification in the I-V curve; these are all characteristics that are typical of KCa currents...
July 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28707739/angiotensin-ii-preconditioning-is-associated-with-increased-pkc%C3%AE%C2%B5-pkc%C3%AE-ratio-and-prosurvival-kinases-in-mitochondria
#5
Rebeca E Nuñez, Sabzali Javadov, Nelson Escobales
Angiotensin II preconditioning (APC) has been shown to reproduce the cardioprotective effects of ischaemic preconditioning (IPC), however, molecular mechanisms mediating the effects of APC remain unknown. In this study, Langendorff-perfused rat hearts were subjected to IPC, APC or both (IPC/APC) followed by ischaemia-reperfusion (IR), to determine translocation of PKCε, PKCδ, Akt, Erk1/2, JNK, p38 MAPK and GSK-3β to mitochondria as an indicator of activation of the protein kinases. In agreement with previous observations, IPC, APC and IPC/APC increased the recovery of left ventricular developed pressure (LVDP), reduced infarct size (IS) and lactate dehydrogenase (LDH) release, compared to controls...
July 14, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28699280/dopamine-d1-receptors-induce-apoptosis-of-osteosarcoma-cells-via-changes-of-mapk-pathway
#6
Jun Gao, Feng Gao
This study explored the effects and mechanisms of dopamine D1 receptors (DR1) activation on the apoptosis of osteosarcoma cells (OS732).The DR1 agonist SKF-38393 decreased the viability of OS732 cells and increased their rate of apoptosis, whereas the DR1 antagonist SCH-23390 abolished the effects of SKF-38393. In OS732 cells, overexpression of DR1 increased the rate of apoptosis, caspase-9 and -3 expression, and the release of cytochrome c (Cyt c), reduced Bcl-2 expression, inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and induced phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK)...
July 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28699234/investigation-of-morin-induced-insulin-secretion-in-cultured-pancreatic-cells
#7
Mang Hung Lin, Chia-Chen Hsu, Jenshinn Lin, Juei Tang Cheng, Ming Chang Wu
Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in diabetes. Insulin secretion has been demonstrated to increase following the administration of morin. The present study is designed to investigate the potential mechanism(s) of morin-induced insulin secretion in the MIN6 cell line. First, we identified that morin induced a dose-dependent increase in insulin secretion and intracellular calcium content in MIN6 cells. Morin potentiated glucose-stimulated insulin secretion (GSIS). Additionally, we used siRNA for the ablation of imidazoline receptor protein (NISCH) expression in MIN6 cells...
July 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28696542/-pro-renin-receptor-activation-increases-profibrotic-markers-and-fibroblast-like-phenotype-through-mapk-dependent-ros-formation-in-mouse-renal-collecting-duct-cells
#8
Alexis A Gonzalez, Leonardo Zamora, Cristian Reyes-Martinez, Nicolas Salinas-Parra, Nicole Roldan, Catherina A Cuevas, Stefanny Figueroa, Alex Gonzalez-Vergara, Minolfa C Prieto
Recent studies suggested that activation of the PRR upregulates profibrotic markers through reactive oxygen species (ROS) formation; however, the exact mechanisms have not been investigated in CD cells. We hypothesized that activation of the PRR increases the expression of profibrotic markers through MAPK-dependent ROS formation in CD cells. Mouse renal CD cell line (M-1) was treated with recombinant prorenin plus ROS or MAPK inhibitors and PRR-shRNA to evaluate their effect on the expression of profibrotic markers...
July 11, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28688153/aqp4-knockout-aggravation-of-isoprenaline-induced-myocardial-injury-is-mediated-by-p66shc-and-endoplasmic-reticulum-stress
#9
Yusi Cheng, Jie Chao, Dezai Dai, Yin Dai, Dongdong Zhu, Bicheng Liu
Aquaporin 4 (AQP4) is a type of water channel protein that maintains the water balance of cardiomyocytes. However, the physiological role of AQP4 in cardiovascular disease is poorly understood. We wanted to explore whether p66Shc and endoplasmic reticulum stress participates in AQP4 knockout (KO)-mediated cardiac injury. There were two types of mice: AQP4 knockout and wild-type mice. Each type was randomly divided into three groups: Control group, isoprenaline stimulation group (ISO, 1 mg/kg, s.c., 5 d), and apocynin treatment group (APO, 100 mg/kg, p...
July 8, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28688148/adipose-derived-mesenchymal-stem-cells-therapy-for-acute-kidney-injury-induced-by-ischemia-reperfusion-in-a-rat-model
#10
Jian-Bo Zhang, Xiao-Qiao Wang, Guo-Lin Lu, Huan-Sen Huang, Shi-Yuan Xu
Acute kidney injury (AKI) represents a group of complicated syndromes with a high mortality rate. The administration of adipose-derived mesenchymal stem cells (ADMSCs) has been tested as a possible treatment method for AKI. The long-term evaluation of AKI induced by ischemia/reperfusion (IR) and the probable renal protection of ADMSCs are limited. In this study we have established a rat AKI model induced by IR and investigated the possible protective effects of ADMSCs. Adult Sprague-Dawley (SD) rats were divided into three groups (n=6/each group)...
July 8, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28686288/distribution-of-cyp2c8-and-cyp2c9-amino-acid-substitution-alleles-in-south-indian-diabetes-patients-a-genotypic-and-computational-protein-phenotype-study
#11
Durga Koteswara Rao, Dwarakanath K Murthy, Nazia Sultana Shaik, Babajan Banaganapalli, Kumar Swami Konda, Hanumantha P Rao, Eswar Ganti, Ahmed A Zuheir, Ashraf El-Harouni, Ramu Elango, Imran Ali Khan, Noor Ahmad Shaik
The CYP2C8 and CYP2C9 are two major isoforms of the cytochrome P450 enzyme family, which is involved in drug response, detoxification, and disease development. This study describes the differential distribution of amino acid substitution variants of CYP2C8 (*2-I269F & *3-R139K) and CYP2C9 (*2-C144R & *3-L359A) genes in 234 type 2 diabetes mellitus (T2DM) patients and 218 healthy controls from Andhra Pradesh, South India. Single locus genotype analysis has revealed that homozygous recessive genotypes of 2C8*2-TT (p=<0...
July 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28682475/hypertonic-saline-inhibits-airway-smooth-muscle-contraction-by-inhibiting-ca-2-sensitization
#12
Xiao-Cao Liu, Qian Wang, Yu-Shan She, Shu Chen, Xi Luo, Hao Xu, Dun-An Zang, Wen-Jing Zhang, Jun-Ying Qiu, Bei-Bei Liu, Jinhua Shen, Yong-Bo Peng, Ping Zhao, Lu Xue, Weiwei Chen, Li-Qun Ma, Xiangning Fu, Jingyu Chen, Qing-Hua Liu, Meng-Fei Yu
The effects of hypertonic solution on airway smooth muscle (ASM) contraction and the underlying mechanisms are largely unknown. We found that hypertonic saline (HS) inhibited acetylcholine (ACh)-induced contraction of ASM from the mouse trachea and human bronchi. In single mouse ASM cells (ASMCs), ACh induced an increase in intracellular Ca(2+) that was further enhanced by 5% NaCl, indicating that the HS-induced inhibition of ASM contraction was not mediated by a decrease in cytosolic Ca(2+) . The Rho-associated kinase (ROCK) inhibitor Y-27632 relaxed ACh-induced precontraction of mouse tracheal rings...
July 6, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28681408/role-of-peripheral-vascular-resistance-as-an-indicator-of-cardiovascular-abnormalities-in-patients-with-parkinson-s-disease
#13
Monika Zawadka-Kunikowska, Joanna Słomko, Małgorzata Tafil-Klawe, Jacek J Klawe, Agnieszka Cudnoch-Jędrzejewska, Julia L Newton, Paweł Zalewski
The aim of this study was to evaluate cardiovascular autonomic modulation in response to an orthostatic stress in healthy subjects and Parkinson's disease (PD). The study included 47 controls and 56 PD patients divided into groups (vasoconstrictor PD, vasodilator PD, control) according to vasodilation/vasoconstriction response during 70° head up tilt test. Using Impedance cardiography (ICG) and electrocardiography (ECG) we measured stroke volume, cardiac output, left ventricular work index, left ventricular ejection time, acceleration index, index of contractility, Heather index, thoracic fluid content, total peripheral resistance, total arterial compliance...
July 5, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28675498/antitumor-bioactive-peptides-isolated-from-marine-organisms
#14
REVIEW
Haibo Xing, Mengting Tong, Nanyu Jiang, Xiaomin Zhang, Hong Hu, Hongming Pan, Da Li
Marine organisms are an important source of antitumor active substances. Thus, pharmaceutical research in recent years has focused on exploring new antitumor drugs derived from marine organisms, and, many peptide drugs with strong antitumor activities have been successfully extracted. Based on different mechanisms, this paper reviews the research on several typical antitumor bioactive peptides in marine drugs and the latest progress therein. Additionally, the development prospects for these antitumor bioactive peptide-based drugs are discussed so as to provide a reference for future research in this field...
July 4, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28664617/down-regulation-of-long-noncoding-rna-malat1-by-rna-interference-inhibits-proliferation-and-induces-apoptosis-in-multiple-myeloma
#15
Hui Liu, Huihan Wang, Bin Wu, Kun Yao, Aijun Liao, Miao Miao, Yang Li, Wei Yang
Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by abnormal proliferation of monoclonal plasma cells in the bone marrow. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an evolutionarily highly conserved long non-coding RNA was originally identified in metastatic non-small cell lung cancer and has been reported to be up-regulated in many other cancers. However, the function of MALAT1 in MM remains unknown. In the present study, by transfecting MM cells with MALAT1-specific short hairpin RNA (shRNA) expression plasmids, the role of MALAT1 in the proliferation and apoptosis of MM cells was investigated in vitro, and the tumorigenicity of MALAT1-silenced cells was evaluated in vivo...
June 30, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28656701/salinomycin-overcomes-acquired-tamoxifen-resistance-through-aib1-and-inhibits-cancer-cell-invasion-in-endocrine-resistant-breast-cancer
#16
Suwisit Manmuan, Nithidol Sakunrangsit, Wannarasmi Ketchart
Salinomycin is a monocarboxylic polyether ionophore isolated from Streptomyces albus. It has been widely used as an antibiotic in veterinary medicine in poultry. A recent study demonstrated that salinomycin selectively inhibits human breast cancer stem cells; one possible mechanism of tamoxifen resistance. Our results show that salinomycin is effective in inhibiting MCF-7/LCC2 and MCF-7/LCC9 cell lines which are well-established endocrine resistant cells and has a synergistic effect in combination with tamoxifen using MTT proliferation assay...
June 28, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28656698/lower-muscle-tissue-is-associated-with-higher-pulse-wave-velocity-a-systematic-review-and-meta-analysis-of-observational-study-data
#17
Alexander J Rodríguez, Md Nazmul Karim, Velandai Srikanth, Peter Ebeling, David Scott
Muscle loss and arterial stiffness share common risk factors and are commonly seen in the elderly. We aimed to synthesise the existing literature on studies that have examined this association. We searched electronic databases for studies reporting correlations or associations between a measure of muscle tissue and a measure of arterial stiffness. Meta-analysis was conducted using Fisher's Z-transformed r-correlation (rZ ) values. Pooled weighted rZ and 95% confidence intervals were calculated in an inverse-variance, random-effects model...
June 28, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28649767/the-use-of-antioxidant-agents-for-chemotherapy-induced-peripheral-neuropathy-treatment-in-animal-models
#18
REVIEW
Larissa Feitosa Carvalho, Ana Maria Fantini Silva, Adriana Andrade Carvalho
Antineoplastic drugs such as Cisplatin, Oxaliplatin, Paclitaxel and Vincristin are widely used in the treatment for several both solid and blood tumours. However, the severity of peripheral neuropathy caused by these agents can affect the patient's quality of life. The major symptoms of Chemotherapy-Induced Peripheral Neuropathy (CIPN) involve: sensory loss, paresthesia, dysesthaesia, numbness, tingling, temperature sensitivity, allodynia and hyperalgesia, in a "stocking and glove" distribution. Why many different chemotherapeutic agents result in similar neuropathy profiles is unclear...
June 26, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28640960/ferulic-acid-alleviates-symptoms-of-preeclampsia-in-rats-by-upregulating-vascular-endothelial-growth-factor
#19
Weiyan Gong, Jipeng Wan, Qing Yuan, Quanzhan Man, Xiaojing Zhang
Preeclampsia is a complication affecting pregnant women worldwide, which leads to maternal and fetal morbidity and mortality. In this study, we evaluated the efficacy of ferulic acid (FA) on an N(ω) -nitro-L-arginine methyl ester hydrochloride (L-NAME) induced rat model of preeclampsia. L-NAME was administered to pregnant rats to induce preeclampsia. 48 rats were divided into three experimental groups (n=16 each): control group, preeclampsia group and preeclampsia with FA treatment (preeclampsia+FA). Physiological characteristics such as urine volume, total urine protein and blood pressure were assessed...
June 22, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28640933/could-ivabradine-be-a-new-treatment-for-the-short-qt-syndrome
#20
EDITORIAL
Jules C Hancox
The short QT syndrome (SQTS) is a rare condition involving accelerated ventricular repolarization, abbreviated rate-corrected (QTc ) QT intervals on the electrocardiogram (ECG), poor rate adaptation of the QT interval, and an increased risk of atrial and ventricular arrhythmias and of sudden cardiac death (1-3). This article is protected by copyright. All rights reserved.
June 22, 2017: Clinical and Experimental Pharmacology & Physiology
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