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Clinical and Experimental Pharmacology & Physiology

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https://www.readbyqxmd.com/read/27896845/stat3-down-regulation-induces-mitochondria-dependent-g2-m-cell-cycle-arrest-and-apoptosis-in-esophageal-carcinoma-cells
#1
Dan Shao, Jie Ma, Chao Zhou, Jia-Nan Zhao, Lu-Lu Li, Tong-Jian Zhao, Xi-Lei Ai, Ping Jiao
STAT3 is persistently activated in a wide variety of human tumors, and aberrant STAT3 activity promotes tumor growth, invasion and metastasis. To explore STAT3 down-regulation in human esophageal cancer cells, cell proliferation, apoptosis and mitochondrial mechanisms were explored in esophageal carcinoma TE1 cell cultures. We demonstrate for the first time that STAT3 down-regulation by RNAi is sufficient to inhibit esophageal cancer cell proliferation inducing cell apoptosis. Further, we demonstrate that mitochondrial transmembrane potential is impaired thereby leading to collapsed mitochondrial membrane potential, abnormal mitochondrial membrane depolarization, nuclear DNA fragmentation and cell cycle G2/M arrest under the conditions of STAT3 down-regulation...
November 29, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27885699/strains-of-group-b-streptococci-from-septic-patients-induce-platelet-activation-via-toll-like-receptor-2
#2
Xiaoyan Liu, Hongyun Liu, Xianming Luo, Ping Zhang, Yanmin Gao, Shuangfeng Xie, Kang Xu, Jianxing Chang, Liping Ma
Group B Streptococcus (GBS) causes life-threatening bacterial sepsis, especially in newborns and pregnant women. Patients suffering from sepsis often display low platelet counts, characterized by thrombocytopenia, because of platelet activation. In the present study, the roles of six GBS strains from septic patients in platelet aggregation, as well as the underlying mechanisms, were investigated. Incubation of platelets with three of the strains induced platelet aggregation, increased the secretion of cellular adhesin molecule CD62P and activation of GPIIb/IIIa...
November 25, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27873387/physical-exercise-remodels-visceral-adipose-tissue-and-mitochondrial-lipid-metabolism-in-rats-fed-a-high-fat-diet
#3
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Sara Becerril, Beatriz Ramírez, I O Gonçalves, Jorge Beleza, Gema Frühbeck, António Ascensão, José Magalhães
We aimed to investigate the effects of two physical exercise models, voluntary physical activity (VPA) and endurance training (ET) as preventive and therapeutic strategies, respectively, on lipid accumulation regulators and mitochondrial content in VAT of rats fed a high-fat diet (HFD). Sprague Dawley rats (6 wks old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets: standard (S, 35 kcal% fat) or HFD (71 kcal% fat). The VPA groups had free access to wheel running during the entire protocol...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27873355/isoquercitrin-protects-against-pulmonary-hypertension-via-inhibiting-pasmcs-proliferation
#4
Yongtao Zhang, Yuqian Cui, Wei Deng, Hao Wang, Weidong Qin, Chengmin Huang, Chen Li, Jianning Zhang, Yuan Guo, Dawei Wu, Haipeng Guo
Pulmonary vascular remodeling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension (PAH), and pulmonary arterial smooth muscle cells (PASMCs) proliferation impact the long-term prognosis of the patient. Isoquercitrin (IQC) is a flavonoid with anti-oxidative, anti-inflammatory and anti-proliferative activations. This study aimed to investigate whether IQC could prevent PASMCs proliferation and vascular remodeling in monocrotaline (MCT) induced PAH. Male Wistar rats were administered with vehicle or 0...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27873337/age-related-common-mirna-polymorphism-associated-with-severe-toxicity-in-lung-cancer-patients-treated-with-platinum-based-chemotherapy
#5
Chao Fang, Xiang-Ping Li, Wei-Jing Gong, Na-Yiyuan Wu, Jie Tang, Ji-Ye Yin, Xi Li, Wei Zhang, Hong-Hao Zhou, Zhao-Qian Liu
Platinum-based chemotherapy toxicity severely impedes successful treatment in lung cancer patients. MicroRNAs (miRs) have a significant impact on the occurrence and survival rate of lung cancer. The purpose of this study was to investigate the association between common miRNA variants and platinum-based chemotherapy toxicity in lung cancer patients. A total of 8 functional SNPs of miRNA were genotyped in 408 lung cancer patients by MALDI-TOF mass spectrometry. All the patients were histologically confirmed as lung cancer, and were treated with platinum-based chemotherapy for at least two cycles...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27864839/reduction-of-the-foreign-body-response-and-neuroprotection-by-apyrase-and-minocycline-in-chronic-cannula-implantation-in-the-rat-brain
#6
Linda Hayn, Linda Deppermann, Michael Koch
Implantation of electrodes or cannulae into the brain is accompanied by a tissue response referred to as foreign body response. Adenosine triphosphate (ATP) is one of the signalling molecules released by injured cells which mediate the chemoattraction of microglial cells. The constitutive release of pro-inflammatory and cytotoxic substances by microglial cells in chronic implants exacerbates neuronal cell death and the immune response. This study aimed to interfere with the initial events of the foreign body response in order to mitigate neurotoxicity and inflammation...
November 19, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27864828/maternal-na-intake-induces-renal-function-injury-in-rats-prevented-by-a-short-term-angiotensin-converting-enzyme-inhibitor
#7
Natalie E Ribeiro, E V Cabral, Regina S Aires, Leucio D Vieira-Filho, Valdilene S Ribeiro, Daianna R M Gonçalves, Luis P N C Borges, Ismaela M F Melo, Cintia G M Ferreira, Valeria Wanderley-Teixeira, Álvaro A C Teixeira, Anísio F Soares, Ana D O Paixão
The Na(+) -ATPase, a secondary pump in the proximal tubule, is only weakly responsive to angiotensin II in adult offspring exposed perinatally to high Na(+) intake. We have investigated whether the offspring from mothers given 0.3 M NaCl show an ineffective angiotensin II action to increase in blood pressure. It was hypothesized that functional alterations at adult life are associated with the number angiotensin II-positive cells in the developing kidney, with increased oxidative stress in maternal/foetal organs, or with morphometrical changes in placentas...
November 19, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27859493/connexin32-deficiency-is-associated-with-liver-injury-inflammation-and-oxidative-stress-in-experimental-non-alcoholic-steatohepatitis
#8
Taynã Cristina Tiburcio, Joost Willebrords, Tereza Cristina da Silva, Isabel Veloso Alves Pereira, Marina Sayuri Nogueira, Sara Crespo Yanguas, Michaël Maes, Elisangela Dos Anjos Silva, Maria Lucia Zaidan Dagli, Inar Alves de Castro, Cláudia Pinto Oliveira, Mathieu Vinken, Bruno Cogliati
Non-alcoholic steatohepatitis is a highly prevalent liver pathology featured by hepatocellular fat deposition and inflammation. Connexin32, which is the major building block of hepatocellular gap junctions, has a protective role in hepatocarcinogenesis and is downregulated in chronic liver diseases. However, the role of connexin32 in non-alcoholic steatohepatitis remains unclear. Connexin32(-/-) mice and their wild-type littermates were fed a choline-deficient high-fat diet. The manifestation of non-alcoholic steatohepatitis was evaluated based on a battery of clinically relevant read-outs, including histopathological examination, diverse indicators of inflammation and liver damage, in-depth lipid analysis, assessment of oxidative stress, insulin and glucose tolerance, liver regeneration and lipid-related biomarkers...
November 17, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27862163/the-effects-of-high-sodium-intake-on-systemic-blood-pressure-and-vascular-responses-in-spontaneously-diabetic-wbn-kob-lepr-fa-fa-rats
#9
Yoshiichi Takagi, Haruno Kadowaki, Ikumi Kobayashi, Kaoru Ito, Katsuaki Ito, Mitsuyuki Shirai, Fumitoshi Asai
The prevalence of type 2 diabetes mellitus (T2DM) and hypertension has markedly increased worldwide. The purpose of the present study was to examine the effects of a high-salt intake on the systolic blood pressure (SBP) and vascular responses in WBN/Kob-Lepr(fa/fa) (WBKDF) rats, a new spontaneous animal model of T2DM. Male WBKDF rats and age-matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal-sodium (0.26%, NS) diet or high-sodium (8%, HS) diet for 14 weeks: 1) Wistar rats on NS diet (Wistar-NS); 2) Wistar rats on HS diet (Wistar-HS); 3) WBKDF rats on NS diet (WBKDF-NS); 4) WBKDF rats on HS diets (WBKDF-HS)...
November 15, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27862177/decreased-percentage-of-nkg2d-nk-cells-in-patients-with-incident-onset-of-type-1-diabetes
#10
Yupan Zhang, Haifeng Wang, Xiaoqian Lou, Xiaozhang Qu, Lichao Gao, Xiaolei Liu, Man Li, Hui Guo, Yanfang Jiang
Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency owing to autoimmune destruction of the pancreatic β cells. A significant decrease in NK cells in peripheral blood has been observed in patients with untreated T1DM. In the present study, we aimed to explore the role of NK cells and their subsets in young T1DM patients. A total of 30 children and adolescents with untreated T1DM and 27 healthy controls (HC) were recruited in this study. Flow cytometry analysis indicated that the percentage of peripheral blood CD3-CD56+ NK cells and NK cells subsets (CD56bright, CD56dim and CD56neg), were significantly decreased in the T1DM patients compared to healthy controls...
November 14, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27862165/grk2-%C3%AE-arrestin-mediates-arginine-vasopressin-induced-cardiac-fibroblast-proliferation
#11
Yunxuan Chen, Feifei Xu, Lingling Zhang, Xiaojun Wang, Yifan Wang, AnthonyYiu-Ho Woo, Weizhong Zhu
Cardiac fibrosis is a pathological feature commonly foundinheartsexposed to hemodynamic orneurohormonal stress. Elevated levels of arginine vasopressin (AVP) are closely associated with the progression ofheart failure and could be an underlyingcauseof cardiac fibrosis. The aim of this study is to characterize the effect of AVP on neonatal rat cardiac fibroblasts (NRCFs) and to illustrate itssignallingmechanism. The proliferative effect of AVP was assessed by methylthiazolyldiphenyl-tetrazoliumassay and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, and the amounts of cellular signallingproteins α-smooth muscle actin(α-SMA),matrix metalloproteinase (MMP) 2, MMP9, and phosphorylated ERK1/2 were determined by Western blotting...
November 14, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27862161/%C3%AE-eudesmol-suppresses-allergic-reactions-via-inhibiting-mast-cell-degranulation
#12
Na-Ra Han, Phil-Dong Moon, Ka-Jung Ryu, Jae-Bum Jang, Hyung-Min Kim, Hyun-Ja Jeong
The regulatory effect of β-eudesmol, which is an active constituent of Pyeongwee-San (KMP6), is evaluated for allergic reactions induced by mast cell degranulation. Phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cell line, HMC-1 cells, and compound 48/80-stimulated rat peritoneal mast cells (RPMCs) are used as the in vitro models; mice models of systemic anaphylaxis, ear swelling, and IgE-dependent passive cutaneous anaphylaxis (PCA) are used as the in vivo allergic models...
November 14, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27862197/gremlin1-promotes-carcinogenesis-of-glioma-in-vitro
#13
Yongchang Guan, Wen Cheng, Cunyi Zou, Tingzhong Wang, Zhi Cao, Anhua Wu
As the most prevalent and lethal type of brain tumors, gliomas, especially the malignant ones, are relatively resistant to the conventional therapies. Gremlin 1 (GREM1) is a secreted glycoprotein that is implicated in the maintenance of cancer stem cells in tumor hierarchy. In the current study, the role of GREM1 in the carcinogenesis of glioma was studied using a knockdown approach. We first examined the expression level of GREM1 in the clinical samples, and then evaluated the effect of GREM1 knockdown on the viability and colony formation capacity of U87-MG cells...
November 8, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27813192/naltrexone-changes-the-expression-of-lipid-metabolism-related-proteins-in-the-endoplasmic-reticulum-er-stress-induced-hepatic-steatosis-in-mice
#14
Azam Moslehi, Fatemeh Nabavizadeh, Ali Zekri, Fatemeh Amiri
Endoplasmic reticulum (ER) stress is closely associated with several chronic diseases such as obesity, atherosclerosis, type 2 diabetes, and hepatic steatosis. Steatosis in hepatocytes may also lead to disorders such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), fibrosis, and possibly cirrhosis. Opioid peptides are involved in triglyceride and cholesterol dysregulation. Naltrexone also attenuates ER stress induced hepatic steatosis in mice. In this study, we evaluated the effects of naltrexone on the expression of lipid metabolism-related nuclear factors and enzymes in the ER stress induced hepatic steatosis...
November 4, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27809360/drug-resistance-and-cancer-stem-cells-the-shared-but-distinct-roles-of-hypoxia-inducible-factors-hif1%C3%AE-and-hif2%C3%AE
#15
Jennifer Petra Schöning, Michael Monteiro, Wenyi Gu
Chemotherapy resistance is a major contributor to poor treatment responses and tumour relapse due to the action of cancer stem cells (CSCs). Mounting evidence suggests these CSCs are reliant on low oxygen conditions and hypoxia-inducible factors 1α and 2α (HIF1α and HIF2α) to maintain their stem cell features. Further research in the last decade has begun to clarify the functional differences between the two HIFα subtypes; here, we review and discuss these differences in relation to CSC drug resistance...
November 3, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27809359/renal-function-in-hiv-hbv-coinfected-and-hbv-monoinfected-patients-on-a-long-term-treatment-with-tenofovir-in-real-life-setting
#16
Laura Milazzo, Cristina Gervasoni, Felicia Stefania Falvella, Dario Cattaneo, Cristina Mazzali, Paola Ronzi, Francesca Binda, Stefania Cheli, Salvatore Sollima, Spinello Antinori
The HIV/HBV coinfection is likely associated with increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV monoinfected patients on long-term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP-binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co-infected and 34 HBV monoinfected patients were commenced on TDF...
November 3, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27809355/aliskiren-protects-against-myocardial-ischemia-reperfusion-injury-via-an-endothelial-nitric-oxide-synthase-dependent-manner
#17
Yu Chen, Guoliang Meng, Wenli Bai, Yan Ma, Liping Xie, Naila Altaf, Yanning Qian, Yi Han, Yong Ji
Aliskiren, a direct renin inhibitor, was shown potent ability to attenuate hypertension. Our previous research has found that aliskiren protected against myocardial ischemia-reperfusion (I/R) injury and enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) in spontaneously hypertensive rats. However, whether the cardioprotective effect of aliskiren against myocardial I/R injury was eNOS-dependent is unknown. In the present study, 12-week-old male eNOS knockout (eNOS(-/-) ) and wild-type C57BL/6J mice (WT) were orally administrated with the dose of 50 mg/kg/day of aliskiren...
November 3, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27805296/the-sensitivity-of-head-and-neck-carcinoma-cells-to-statins-is-related-to-the-expression-of-their-ras-expression-status-and-statin-induced-apoptosis-is-mediated-via-suppression-of-the-ras-erk-and-ras-mtor-pathways
#18
Masanobu Tsubaki, Daichiro Fujiwara, Tomoya Takeda, Toshiki Kino, Yoshika Tomonari, Tatsuki Itoh, Motohiro Imano, Takao Satou, Katsuhiko Sakaguchi, Shozo Nishida
Statins induce apoptosis of tumor cells by inhibiting the prenylation of small G-proteins. However, the details of the apoptosis-inducing mechanisms remain poorly understood. The present study showed that the induction of apoptosis by statins in four different human head and neck squamous cell carcinoma (HNSCC) cell lines, HSC-3, HEp-2, Ca9-22, and SAS cells was mediated by increased caspase-3 activity. Statins induced apoptosis by the suppression of geranylgeranyl pyrophosphate biosynthesis. Furthermore, statins decreased the levels of phosphorylated ERK and mTOR by inhibiting the membrane localization of Ras and enhancing Bim expression in HSC-3 and HEp-2 cells...
November 2, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27797410/regulation-of-microvascular-flow-and-metabolism-an-overview
#19
Michelle A Keske, Renee M Dwyer, Ryan D Russell, Sarah J Blackwood, Aascha A Brown, Donghua Hu, Dino Premilovac, Stephen M Richards, Stephen Rattigan
Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin receptors on myocytes to stimulate glucose transporter 4 (GLUT 4) translocation to the cell surface membrane, enhancing glucose uptake. However, an additional role of insulin that is often under-appreciated is its action to increase muscle perfusion thereby improving insulin and glucose delivery to myocytes...
October 31, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27797409/a-tumor-promoting-role-of-th9-cells-in-hepatocellular-carcinoma-through-ccl20-and-stat3-pathways
#20
Hongwu Tan, Shuyun Wang, Ludong Zhao
Hepatocellular carcinoma (HCC) is a common and aggressive human malignancy. An imperative demand is present for a better understanding of the functions and regulations of the immune system and how they affect HCC pathogenesis. Recently, a group of interleukin 9 (IL-9)-producing CD4(+) T cells, termed Th9 cells, has been described in mice and humans with both tumor-inhibiting as well as tumor-promoting effects. The specific roles of Th9 cells in human HCC are not entirely understood. Here, we examined the frequencies and functions of IL-9-producing Th9 cells in HCC patients...
October 31, 2016: Clinical and Experimental Pharmacology & Physiology
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