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Clinical Science (1979-)

Xiaojing Qiao, Yahui Liu, Peiqiang Li, Zhongzhong Chen, Huili Li, Xueyan Yang, Richard H Finnell, Zhangmin Yang, Ting Zhang, Bin Qiao, Yufang Zheng, Hongyan Wang
The planar cell polarity (PCP) pathway is critical for proper embryonic development of the neural tube and heart. Mutations in these genes have previously been implicated in the pathogenesis of neural tube defects (NTDs), but not in congenital heart defects (CHDs) in humans. We systematically identified the mutation patterns of CELSR1-3 , one family of the core PCP genes, in human cohorts composed of 352 NTD cases, 412 CHD cases, and matched controls. A total of 72 disease-specific rare novel coding mutations were identified, of which 37 were identified in CHD cases, and 36 were identified in NTD patients...
October 18, 2016: Clinical Science (1979-)
Joan Raouf, Fariborz Mobarrez, Karin Larsson, Per-Johan Jakobsson, Marina Korotkova
Microsomal prostaglandin E2 synthase-1 (mPGES-1) constitutes an essential player of inflammation and is involved in the pathogenesis of rheumatoid arthritis (RA). Platelets participate in the regulation of inflammatory processes by the release of pro-inflammatory mediators and platelet-derived microparticles (PMPs). However, the role of the inducible mPGES-1/PGE2 pathway on platelet functions has not been investigated. Here we report a significant impact of mPGES-1 on platelet functions during inflammation...
October 7, 2016: Clinical Science (1979-)
Chang-Yien Chan, Kar-Hui Ng, Jinmiao Chen, Jinhua Lu, Caroline Guat-Lay Lee, Puay-Hoon Tan, Stanley C Jordan, He Henry Yang, Hui-Kim Yap
Our established interleukin-13 ( IL-13 ) overexpression rat model of minimal change-like nephropathy provided a platform to study the molecular signalling pathways in T-helper 2 (Th2) cytokine associated minimal change nephrotic syndrome. We hypothesized that IL-13 may act directly on podocytes, causing podocyte foot process effacement and hence proteinuria in our rat model of minimal change-like nephropathy. This study aimed firstly to delineate the glomerular "gene signature" associated with IL-13-mediated dysregulation of podocyte related proteins, and subsequently to investigate the role of the differentially regulated genes in IL-13-mediated podocyte injury...
October 5, 2016: Clinical Science (1979-)
Wei-Ming Li, Yi-Fan Zhao, Guo-Fu Zhu, Wen-Hui Peng, Meng-Yun Zhu, Xue-Jing Yu, Wei Chen, Da-Chun Xu, Ya-Wei Xu
BACKGROUND: Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the DUSP family, which is characterized by its dual specific phosphatase activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear...
October 4, 2016: Clinical Science (1979-)
Yu Han, Xiang Liao, Zhao Gao, Sufei Yang, Caiyu Chen, Yukai Liu, Wei Eric Wang, Gengze Wu, Xiongwen Chen, Pedro A Jose, Ye Zhang, Chunyu Zeng
Cardiac troponin I (cTnI), a biomarker for myocardial damage and risk stratification, may be involved in the pathogenesis of cardiovascular diseases, which was ascribed to the effect of cTnI auto-antibodies. Whether or not cTnI itself has a direct impact on acute myocardial injury is unknown. To exclude the influence of cTnI antibody on the cardiac infarct size, we studied the effect of cTnI shortly after myocardial ischemia-reperfusion (I/R) injury when cTnI antibodies were not elevated. Pretreatment with cTnI augmented the myocardial infarct size caused by I/R, accompanied by an increase in inflammatory markers in the blood and myocardium...
September 28, 2016: Clinical Science (1979-)
Dong-Xu He, Feng Gu, Jian Wu, Xiao-Ting Gu, Chun-Xiao Lu, Ai-Qin Mao, Guang-Yuan Zhang, Zhong-Yang Ding, Jin-Ke Wang, Jun-Jun Hao, Li Fu, Xin Ma
Chemotherapeutic response is critical for the successful treatment and good prognosis in cancer patients. In this study, we analyzed the gene expression profiles of preoperative samples from ER-negative breast cancer patients with different responses to taxane-anthracycline-based (TA-based) chemotherapy, and identified a group of genes that was predictive. Pregnancy specific beta-1-glycoprotein 1 (PSG1) played a central role within signaling pathways of these genes. Inhibiting the PSG1 can effectively reduce chemoresistance via transforming growth factor-β (TGF-β)-related pathway in ER-negative breast cancer cells...
September 21, 2016: Clinical Science (1979-)
Simon G Royce, Anna M Tominaga, Matthew Shen, Krupesh P Patel, Brooke M Huuskes, Rebecca Lim, Sharon D Ricardo, Chrishan S Samuel
Current asthma therapies primarily target airway inflammation (AI) and suppress episodes of airway hyperresponsiveness (AHR) but fail to treat airway remodelling (AWR), which can develop independently of AI and contribute to irreversible airway obstruction. This study compared the anti-remodelling and therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) to that of human amnion epithelial stem cells (AECs) in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic (serelaxin; RLX)...
September 19, 2016: Clinical Science (1979-)
Leah Stiemsma, Marie-Claire Arrieta, Pedro Dimitriu, Jasmine Cheng, Lisa Thorson, Diana Lefebvre, Meghan B Azad, Padmaja Subbarao, Piush Mandhane, Allan Becker, Malcolm Sears, Tobias Kollmann, William Mohn, Brett Finlay, Stuart Turvey
Asthma is a chronic disease of the airways affecting one in ten children in Westernized countries. Recently, our group showed that specific bacterial genera in early life are associated with atopy and wheezing in one-year-old children. However, little is known about the link between the early life gut microbiome and the diagnosis of asthma in preschool age children. To determine the role of the gut microbiota in preschool age asthma, children up to 4 years of age enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified as asthmatic (n = 39) or matched healthy controls (n = 37)...
September 15, 2016: Clinical Science (1979-)
Marie Claude Denis, Denis Roy, Pantea Rahmani Yeganeh, Yves Desjardins, Thibault Varin, Nour Haddad, Devendra Amre, Alain Théophile Sané, Carole Garofalo, Alexandra Furtos, Natalie Patey, Edgard Delvin, Eric Tremblay, Andre Marette, Jean François Beaulieu, Emile Levy
Diets rich in fruits and vegetables may reduce oxidative stress and inflammation via several mechanisms. These beneficial effects may be due to their high polyphenol content. The aims of the present study are to evaluate the preventive and therapeutic aspects of polyphenols in dried apple peel extract (DAPP) on intestinal inflammation while elucidating the underlying mechanisms and clinical benefits. Induction of intestinal inflammation in mice was performed by oral administration of the inflammatory agent DSS at 2...
September 14, 2016: Clinical Science (1979-)
Idoia Gallego, Javier Beaumont, Begoña López, Susana Ravassa, Juan José José Gómez-Doblas, María Ujué Ujué Moreno, Félix Valencia, Eduardo de Teresa, Javier Díez, Arantxa González
MicroRNAs have been associated with cardiomyocyte apoptosis, a process involved in myocardial remodelling in aortic valve (Av) stenosis (AS). Our aim was to analyse whether the dysregulation of myocardial microRNAs was related to cardiomyocyte apoptosis in AS patients. Endomyocardial biopsies were obtained from 28 patients with severe AS (based on pressure gradients and Av area) referred to Av replacement and from necropsies of 10 cardiovascular disease-free control subjects. AS patients showed an increased ( P <0...
September 13, 2016: Clinical Science (1979-)
Cintia Carmos-Silva, Jônathas Almeida, Larissa Macedo, Marcos B Melo, Gustavo Pedrino, Fernanda Santos, Manoel Biancardi, Robson Augusto Souza Santos, Adryano Carvalho, Elizabeth Mendes, Diego Colugnati, Renata Mazaro-Costa, Carlos Castro
Previous studies have demonstrated a protective effect of the Ang-(1-7)/Mas receptor axis on pathological cardiac hypertrophy. Also, the involvement of Mas receptor in the exercise-induced cardiac hypertrophy has been suggested. However, the role of the Ang-(1-7)/Mas receptor on pregnancy-induced cardiac remodeling remains unknown. The objective of this study was to evaluate the participation of the Mas receptor in the development of the cardiac hypertrophy and fibrosis induced by gestation. Female Wistar rats were shared in 3 groups: control , pregnant , and pregnant treated with Mas receptor antagonist A-779 ...
September 13, 2016: Clinical Science (1979-)
Yujia Yuan, Meimei Shi, Lan Li, Jingping Liu, Bo Chen, Younan Chen, Xingxing An, Shuyun Liu, Ruixi Luo, Dan Long, Wengeng Zhang, Philip Newsholme, Jingqiu Cheng, Yanrong Lu
Vasculopathy is a major complication of diabetes. Impaired mitochondrial bioenergetics and biogenesis due to oxidative stress is a critical causal factor for diabetic endothelial dysfunction. Sirt1, a NAD(+)-dependent enzyme, is known to play an important protective role through deacetylation of many substrates involved in oxidative phosphorylation and reactive oxygen species (ROS) generation. Conditioned medium from mesenchymal stem cells (MSCs-CM) has emerged as a promising cell-free therapy due to the trophic actions of MSCs secreted molecules...
September 9, 2016: Clinical Science (1979-)
Yanmei Chen, Chuanxi Zhang, Shuxin Shen, Shengcun Guo, Lintao Zhong, Xinzhong Li, Guojun Chen, Gangbin Chen, Xiang He, Chixiong Huang, Nvqin He, Wangjun Liao, Yulin Liao, Jianping Bin
Delayed administration of bone marrow cells (BMCs) at 2-4 weeks after successful reperfusion in patients with acute myocardial infarction does not improve cardiac function. The reduction in engraftment signals observed following this time interval might impair the effects of delayed BMC treatment. Here, we aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) treatment could increase engraftment signals, enhance the delivery of delayed BMCs, and subsequently attenuate post-infarction cardiac remodeling...
September 8, 2016: Clinical Science (1979-)
Melissa A Wasilewski, Laurel A Grisanti, Jianliang Song, Rhonda L Carter, Ashley A Repas, Valerie D Myers, Erhe Gao, Walter J Koch, Joseph Y Cheung, Arthur M Feldman, Douglas Tilley
V1AR expression is elevated in chronic human heart failure and contributes to cardiac dysfunction in animal models, in part via reduced βAR responsiveness.  While cardiac V1AR overexpression and V1AR stimulation are each sufficient to decrease βAR activity, it is unknown whether V1AR inhibition conversely augments βAR responsiveness.  Further, although V1AR has been shown to contribute to chronic progression of heart failure, its impact on cardiac function following acute ischemic injury has not been reported...
September 2, 2016: Clinical Science (1979-)
Ursula Paula Renó Soci, Tiago Fernandes, Valerio Garrone Barauna, Nara Yumi Hashimoto, Gloria de Fátima Alves Mota, Kaleizu Teodoro Rosa, Maria Claudia Irigoyen, Michael Ian Phillips, Edilamar Menezes de Oliveira
: Aerobic exercise-induced cardiac hypertrophy is a physiological response involving accurate orchestration of gene and protein expression of contractile and metabolic components. The microRNAs: miR-208a, miR-208b and miR-499 are each encoded by a myosin gene and thus are also known as "MyomiRs", regulating several mRNA targets that in turn regulate cardiac hypertrophy and metabolic pathways. AIMS: To understand the role of myomiRs in the fine-tuning of cardiac MHC isoform expression by exercise training-induced physiological hypertrophy...
August 8, 2016: Clinical Science (1979-)
Michael V Autieri
Visceral adipose tissue is a primary site of chronic inflammation in obesity and may contribute to systemic inflammation and development of atherosclerotic vascular disease. Few studies identify molecular mechanisms and secretory pathways which mediate this process. In this edition of Clinical Science, Kwok et al. utilize a transgenic mouse in which dominant-negative c-Jun NH2 terminal kinase (dnJNK) expression is restricted to adipose tissue to implicate JNK-driven expression of adipocyte fatty acid binding protein (A-FABP) in visceral adipose tissue as a key secretory pathway to exacerbate development of atherosclerosis in ApoE-/- mice...
November 1, 2016: Clinical Science (1979-)
Laure B Bindels, Isabelle Leclercq
Gut micro-organisms are recognized as crucial regulators of host immunity and the microbiota has been implicated in several inflammatory, immune, inflammatory or even psychiatric disorders. Therefore the analysis of the complex interactions between gut microbiota and the host is currently under intense investigation. Most of our knowledge stems from the study of animal models while translational research and data in humans are necessary to move the field forward and to evolve to diagnostic and therapeutic application...
November 1, 2016: Clinical Science (1979-)
Shengyuan Luo, Wenhao Xia, Cong Chen, Eric A Robinson, Jun Tao
The discovery of endothelial progenitor cells (EPCs), a group of cells that play important roles in angiogenesis and the maintenance of vascular endothelial integrity, has led to considerable improvements in our understanding of the circulatory system and the regulatory mechanisms of vascular homoeostasis. Despite lingering disputes over where EPCs actually originate and how they facilitate angiogenesis, extensive research in the past decade has brought about significant advancements in this field of research, establishing EPCs as an essential element in the pathogenesis of various diseases...
November 1, 2016: Clinical Science (1979-)
Joanna M Wardlaw, Karen Horsburgh
No abstract text is available yet for this article.
November 1, 2016: Clinical Science (1979-)
Kathleen Atkins, Asish Dasgupta, Kuang-Hueih Chen, Jeff Mewburn, Stephen L Archer
Mitochondrial morphology is governed by the balance of mitochondrial fusion, mediated by mitofusins and optic atrophy 1 (OPA1), and fission, mediated by dynamin-related protein 1 (Drp1). Disordered mitochondrial dynamics alters metabolism, proliferation, apoptosis and mitophagy, contributing to human diseases, including neurodegenerative syndromes, pulmonary arterial hypertension (PAH), cancer and ischemia/reperfusion injury. Post-translational regulation of Drp1 (by phosphorylation and SUMOylation) is an established means of modulating Drp1 activation and translocation to the outer mitochondrial membrane (OMM)...
November 1, 2016: Clinical Science (1979-)
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