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Clinical and Experimental Pharmacology & Physiology

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https://www.readbyqxmd.com/read/28508433/an-investigation-of-the-anti-inflammatory-effects-and-a-potential-biomarker-of-pi3k%C3%AE-inhibition-in-copd-t-cells
#1
Abid Khan, Thomas Southworth, Sally Worsley, Srividya Sriskantharajah, Augustin Amour, Edith M Hessel, Dave Singh
Lymphocyte numbers are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. Phosphatidylinositol-3-kinase delta (PI3Kδ) is involved in lymphocyte activation. We investigated the effect of PI3Kδ inhibition on cytokine release from COPD lymphocytes. We also evaluated phosphorylated ribosomal S6 protein (rS6) as a potential biomarker of PI3Kδ activation. Peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) cells isolated from healthy never smokers (HNS), smokers (S) and COPD patients were stimulated to induce a T cell receptor response...
May 15, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28504843/a-novel-synthetic-chemical-entity-upei-800-is-neuroprotective-in-vitro-and-in-an-in-vivo-rat-model-of-oxidative-stress
#2
Tarek M Saleh, Monique C Saleh, Barry J Connell, Inan Kucukkaya, Alaa S Abd-El-Aziz
In this study, we tested a novel synthetic pyrazole-containing compound, 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile (APPC), as an antioxidant in both in vitro and in vivo models of oxidative stress. In addition, the utility of covalently combining APPC with another well-established antioxidant, lipoic acid (LA), was also tested in both models. The in vitro results demonstrated that pretreatment with APPC in a mixed neuronal-glial culture exposed to oxygen-glucose deprivation (OGD) followed by reoxygenation-refeeding, resulted in significant neuroprotection at concentrations between 2...
May 15, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28502103/reduced-platelet-aggregation-in-women-after-intercourse-a-possible-role-for-the-cyclooxygenase-pathway
#3
Gabriel Mayoral-Andrade, Laura Pérez-Campos-Mayoral, Abraham Majluf-Cruz, Eduardo Perez-Campos Mayoral, Carlos Perezcampos Mayoral, Ana Rocha-Núñez, Margarito Martinez, Edgar Zenteno, Leticia Hernandez-Gonzalez, María Guadalupe López Juan, Alma Dolores Pérez-Santiago, Eduardo Pérez-Campos
We hypothesise that molecules in the cyclooxygenase pathway affect platelet activity when seminal fluid (SF) is present. We considered the influence of SF on platelet aggregation in women, and believe that the prostanoids in SF signalling are significant. Thirty-one female subjects were studied, 20 of whom were sexually active. Male partners were given either aspirin or indomethacin to inhibit cyclooxygenase. The 6-keto prostaglandin F1α (6-keto PGF1α) and prostaglandin E metabolite (PGE-M) in SF were measured by competitive assay...
May 14, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28500767/metformin-for-high-altitude-performance
#4
Martin Burtscher
Metformin has been introduced for treatment of type 2 diabetes but may also have ergogenic properties at high altitude by improving muscle glycogen repletion. However, very little information is available on potential risks associated with the (mis)use of metformin by healthy people. This article is protected by copyright. All rights reserved.
May 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28500760/the-opposite-effects-of-nitric-oxide-donor-s-nitrosoglutathione-on-myocardial-ischemia-reperfusion-injury-in-diabetic-and-non-diabetic-mice
#5
Yi Liu, Chenhai Xia, Rutao Wang, Jinglong Zhang, Tao Yin, Yanzuo Ma, Ling Tao
Nitric oxide is a potent anti-apoptotic and cardioprotective molecule in healthy animals. However, Recent study demonstrates that overexpression of eNOS exacerbates the liver injury in diabetic animals. whether diabetes may also alter NO's biologic activity in ischemic/reperfused heart remains unknown. The present experiment was designed to determine whether the nitric oxide donor, S-nitrosoglutathione, may exert different effects on diabetic and non-diabetic myocardial ischemia/reperfusion (MI/R) injury. Diabetic state was induced in mice by multiple intraperitoneal injections of low-dose streptozotocin (STZ)...
May 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28477368/highly-expressed-long-non-coding-rna-crnde-promotes-cell-proliferation-through-pi3k-akt-signaling-in-non-small-cell-lung-carcinoma
#6
Xiao-Xiong Liu, Han-Peng Xiong, Jiu-Sheng Huang, Kai Qi, Jian-Jun Xu
Recently, numerous studies revealed that long non-coding RNAs (lncRNAs) play complex roles in various lung diseases, while the colorectal neoplasia differentially expressed (CRNDE) functions in non-small cell lung carcinomas (NSCLC) remain largely unknown. In the present study, we investigated the role and mechanism of CRNDE in the progression of NSCLC. The mRNA level of CRNDE in NSCLC patients and cells was detected by qRT-PCR. The influence of CRNDE silencing or over-expression on NSCLC cell proliferation and growth were assessed by MTT and flow cytometry, respectively...
May 6, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28477359/inhibitory-effect-of-the-urothelium-lamina-propria-on-female-porcine-urethral-contractility-effect-of-age
#7
Oladayo Seun Folasire, Russ Chess-Williams, Donna Jayne Sellers
The urethral uroepithelium has been implicated in urethral sensation and maintenance of continence. However, relatively little is known about the function of the urethral urothelium compared with that of the bladder. The aim of the study was to examine the role of the urothelium/lamina propria on contractility of the porcine urethra, along with the influence of nitric oxide, prostaglandins and ageing. Porcine urethral tissues, intact and denuded of urothelium/lamina propria, were mounted in tissue baths and contractions to noradrenaline, phenylephrine and carbachol obtained...
May 6, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28467603/pathophysiology-and-therapeutics-of-premature-ageing-in-chronic-kidney-disease-with-a-focus-on-glycative-stress
#8
Yosuke Hirakawa, Tzu-Ming Jao, Reiko Inagi
Chronic kidney disease (CKD) is a major concern in public health. The pathology of CKD includes premature ageing in the kidney and vessels, which results in a high risk of cardiovascular events and end-stage renal disease. Many factors are involved in premature ageing in CKD, including hormonal imbalance, glycative stress, nitrogenous metabolites, and oxidative stress. Of these, the most important role in premature ageing in CKD is played by glycative stress, namely a massive and unfavorable glycation state, since the kidney is responsible for the clearance of advanced glycation endproducts (AGEs)...
May 3, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28466565/aging-leads-to-impaired-epicutaneous-sensitization-that-causes-attenuated-allergy-and-pulmonary-inflammation-in-mice
#9
Sheila Langier, Shira Benor, Laliv Kadar, Nir Shani, Sara Etkin, Moshe Stark, Ekaterina Bondar, Asaf Aizic, Shmuel Kivity
Aging is associated with altered decreased barrier function in the skin, which can lead to different types of immunoglobulin E (IgE)-mediated sensitization to environmental allergens. Yet, allergen-specific respiratory sensitization among the elderly is not well described. The aim of this study was to investigate the effect of aging on allergic pulmonary inflammation induced by epicutaneous sensitization of mechanically irritated skin in mice. For this purpose, 6-week-, 6-month-, and 18-month-old female BALB/c mice, underwent epicutaneous sensitization with ovalbumin (OVA) or PBS, followed by an inhaled OVA challenge...
May 3, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28464292/rnai-mediated-gene-silencing-of-itpa-using-a-targeted-nanocarrier-apoptosis-induction-in-skbr3-cancer-cells
#10
Fahimeh Charbgoo, Mehrdad Behmanesh, Maryam Nikkhah, Eric G Kane
A pure nucleotide pool is required for high-fidelity DNA replication and prevention of carcinogenesis in living cells. Human inosine triphosphatase (ITPase), encoded by the ITPA gene, plays a critical role in maintaining the purity of the cellular nucleotide pool by excluding nucleotides that enhance mutagenesis. ITPase is a nucleoside triphosphate pyrophosphatase that hydrolyzes the non-canonical nucleotides inosine triphosphate (ITP) and xanthine triphosphate (XTP). The monophosphate products of ITPase reactions are subsequently excluded from the nucleotide pool and the improper substitution of ITP and XTP into DNA and RNA is prevented...
May 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28453233/proteomic-analysis-of-oral-cancer-reveals-new-potential-therapeutic-targets-involved-in-the-warburg-effect
#11
Yi-Ping Huang, Nai Wen Chang
Activation of peroxisome proliferator-activated receptor alpha (PPARα) has been reported to disrupt tumor metabolism and to promote anticancer activity through interfering with the Warburg effect. This study is to investigate whether Warburg effect-related proteins also could be identified in the oral tumor lesions and to explore the functional significance of PPARα in metabolic shift. Five pairs of tongue tumor tissues and adjacent reference tissues obtained from 4-NQO/arecoline induced mouse model were analyzed by 2-D-gel-electrophoresis and LC-MS...
April 28, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28453191/naringenin-prevents-ischemic-stroke-damage-via-anti-apoptotic-and-anti-oxidant-effects
#12
Kaihua Wang, Zhenzhen Chen, Jianmin Huang, Longjian Huang, Ning Luo, Xiulin Liang, Mingkun Liang, Wei Xie
Apoptosis and oxidative stress are considered to be the major factors associated with the development and progression of many ischemic cerebrovascular diseases. Naringenin (NAR) is an abundant flavanone in citrus plants and has been found to exhibit anti-oxidant, anti-carcinogenic and anti-apoptotic effects. This study aimed to investigate the anti-apoptotic and anti-oxidant effects of naringenin on ischemic stroke. In vitro, cortical neuron cells isolated from the brains of neonatal Sprague-Dawley rats were randomly divided into control, oxygen and glucose deprivation/reperfusion (OGD/Rep), NAR-L, NAR-M and NAR-H groups...
April 28, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28440910/subacute-pyridostigmine-exposure-increases-heart-rate-recovery-and-cardiac-parasympathetic-tone-in-rats
#13
Manushree Bharadwaj, Carey Pope, Michael Davis, Stuart Katz, Christian Cook, Lara Maxwell
Heart rate recovery (HRR) describes the rapid deceleration of heart rate after strenuous exercise and is an indicator of parasympathetic tone. A reduction in parasympathetic tone occurs in patients with congestive heart failure, resulting in prolonged HRR. Acetylcholinesterase inhibitors, such as pyridostigmine, can enhance parasympathetic tone by increasing cholinergic input to the heart. The objective of this study was to develop a rodent model of HRR to test the hypothesis that subacute pyridostigmine administration decreases cholinesterase activity and accelerates HRR in rats...
April 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28440887/microrna-regulation-of-extracellular-matrix-components-in-the-process-of-atherosclerotic-plaque-destabilization
#14
REVIEW
Michal Kowara, Agnieszka Cudnoch-Jedrzejewska, Grzegorz Opolski, Pawel Wlodarski
The process of atherosclerotic plaque destabilization, leading to myocardial infarction, is still not fully understood. The pathway - composed of structural and regulatory proteins of the extracellular matrix (ECM) such as collagen, elastin, small leucine-rich proteoglycans, metalloproteinases, cathepsins and serine proteases - is one potential way of atherosclerotic plaque destabilization. The expression of these proteins is controlled by different microRNA molecules. The goal of this paper is to summarize the current investigations and knowledge about ECM in the process of atherosclerotic plaque destabilization, giving special attention to epigenetic expression regulation by microRNA...
April 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28432808/mechanism-of-the-vasorelaxant-effect-induced-by-trans-4-methyl-%C3%AE-nitrostyrene-a-synthetic-nitroderivative-in-rat-thoracic-aorta
#15
Taylena Maria Teófilo, Loeste Arruda-Barbosa, Jussara Mathyelle Rodrigues-Silva, Joyce Karen Lima Vale, Rosivaldo Dos Santos Borges, Gloria Pinto Duarte, Pedro Jorge Caldas Magalhães, Saad Lahlou
Mechanisms underlying the vasorelaxant effects of trans-4-methyl-β-nitrostyrene (T4MeN) were studied in rat aortic rings. In endothelium-intact preparations, T4MeN fully and similarly relaxed contractions induced by phenylephrine (PHE) (IC50 = 61.41 [35.40-87.42] μM) and KCl (IC50 = 83.50 [56.63-110.50] μM). The vasorelaxant effect of T4MeN was unchanged by endothelium removal, pretreatment with L-NAME, indomethacin, tetraethylammonium, ODQ or MDL-12,330A. Under Ca(2+) -free conditions, T4MeN significantly reduced with a similar potency: (i) phasic contractions induced by PHE, but not by caffeine; (ii) contractions due to CaCl2 in aortic preparations stimulated with PHE (in the presence of verapamil) or high KCl; (iii) contractions evoked by the restoration of external Ca(2+) levels after depletion of intracellular Ca(2+) stores in the presence of thapsigargin...
April 22, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429868/clarification-of-serotonin-induced-effects-in-peripheral-artery-disease-observed-through-the-femoral-artery-response-in-models-of-diabetes-and-vascular-occlusion-the-role-of-calcium-ions
#16
Marko Stojanović, Milica Prostran, Radmila Janković, Miroslav Radenković
Recent findings have demonstrated that serotonin is an important participant in the development and progression of peripheral artery diseases. Taking this into consideration, the goals of this study were to investigate the effects of serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic animals, with and without artery occlusion, with a particular focus on determining the role of calcium in this process. Contraction experiments with serotonin on intact and denuded femoral artery rings, in the presence or absence of nifedipine and ouabain (both separately, or in combination), as well as Ca(2+) -free Krebs-Ringer bicarbonate solution were performed...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429857/ndufa4l2-protects-against-ischemia-reperfusion-induced-cardiomyocyte-apoptosis-and-mitochondrial-dysfunction-by-inhibiting-complex-i
#17
Jianhua Li, Caiyan Bai, Junxia Guo, Wanqian Liang, Jingning Long
Myocardial ischemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as mitochondrial dysfunction. The aims of the present study were to investigate whether NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) on myocardial ischemia-reperfusion (I/R) injury and the underlying molecular mechanism. The hypoxia-reperfusion (H/R) model was established in vitro using H9c2 cells to simulate I/R injury. NDUFA4L2 and complex I expression levels were detected using RT-PCR and western blot...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429852/anti-inflammatory-and-retinal-protective-effects-of-capsaicin-on-ischemia-induced-injuries-through-the-release-of-endogenous-somatostatin
#18
Jun Wang, Wenke Tian, Shuaiwei Wang, Wenqiang Wei, Dongdong Wu, Honggang Wang, Li Wang, Ruisheng Yang, Ailing Ji, Yanzhang Li
The mechanisms regarding the retinal protective and anti-inflammatory effects of capsaicin (CAP) remain unclear. Somatostatin is contained in CAP-sensitive sensory neurons, including nerve terminals, from which it can be released by capsaicin. The present study provides a novel neurohumoral regulatory mechanism for CAP-induced-endogenous somatostatin in a retinal ischemic-reperfusion (I/R) mouse model. CAP (0.5 mg kg(-1) ) was injected subcutaneously 5 min after I/R. A selective somatostatin-depleting agent, cysteamine, was applied subcutaneously 4 hours before the experiment to examine the effects of endogenous somatostatin...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429540/silencing-of-astrocyte-elevated-gene-1-inhibits-proliferation-and-migration-and-induces-apoptosis-in-melanoma
#19
Yue Zhang, Ge Peng, Ying Wang, Lixia Cui, Wenqing Wu, Luan Wang, Chengyu Liu, Xiuping Han
Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of ras and c-myc, has been implicated in the development of multiple tumors, yet its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 silencing. Our results showed that silencing of AEG-1 inhibited proliferation of melanoma cells and induced cell cycle arrest, accompanied by reduced levels of cyclinA, cyclinB, cyclinD1, cyclinE and cyclin dependent kinase 2...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429502/involvement-of-erk1-2-in-cx43-depression-induced-by-macrophage-migration-inhibitory-factor-in-atrial-myocytes
#20
Xin Li, Fang Rao, Chun-Yu Deng, Wei Wei, Fang-Zhou Liu, Hui Yang, Zhao-Yu Wang, Su-Juan Kuang, Xiao-Yan Chen, Yu-Mei Xue, Shu-Lin Wu
Connexin 43 (Cx43) plays an important role in the pathogenesis of atrial fibrillation (AF). The present study sought to investigate the effect of macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, on Cx43 expression and activity and determine the intracellular signaling pathways. Cx43 protein and mRNA levels were assayed using immunofluorescence, real-time PCR, and western blot. We found that increased MIF and extracellular regulated protein kinases (ERK) expression was accompanied by a significant reduction in Cx43 protein expression in atrial tissues from patients with AF compared with those with sinus rhythm...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
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