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Clinical Science (1979-)

Chengzhong Zhang, Xin Wang, Yue Chen, Zhouwei Wu, Chao Zhang, Weimin Shi
BACKGROUND: Systemic lupus erythematous (SLE) is an autoimmune disease characterized by production of autoantibodies directed against various autoantigens. But the expression profiles and functions of circRNAs in SLE are still scarce. OBJECTIVES: To explore the roles of circRNA in SLE and its potential diagnostic potential in SLE. METHODS: SLE patients and healthy control subjects were recruited. CD4+ T cellswere isolated, circRNA microarray analysis were used to screen for circRNA candidate in CD4+ T cells...
September 20, 2018: Clinical Science (1979-)
Hongjie Qiao, Yuanyuan Zhang, Wenwen Lin, Yu-Feng Wang, Cristina M Furdui, Qiuling Jiang, Xiao Li, Ting Long, Yunguang Wang, Da-Nian Qin
Increased production of reactive oxygen species (ROS) and inflammation are major contributors to the development and progression of diabetes-associated erectile dysfunction (DMED). As an endogenous anti-oxidant and anti-inflammatory factor, the potential implication of pigment epithelium-derived factor (PEDF) in DMED has not been revealed. To assess the potential antioxidant and anti-inflammatory function of PEDF in DMED, we first demonstrated that PEDF was significantly decreased at the levels of the mRNA and protein in the penis of diabetic rats compared with normal controls...
September 19, 2018: Clinical Science (1979-)
Shuang Cui, Liling Wu, Xiaodan Feng, Huanjuan Su, Zhanmei Zhou, Weihong Luo, Cailing Su, Yajing Li, Meng Shi, Zhichen Yang, Wei Cao
One of the major obstacles to prevent AKI-CKD transition is the lack of effective methods to follow and predict the ongoing kidney injury after an AKI episode. In this study, we test the utility of urinary angiotensinogen (UAGT) for dynamically evaluating renal structural changes and predicting AKI-CKD progression by using both mild and severe bilateral renal ischemia/reperfusion injury mice. UAGT returns to pre-ischemic levels 14 days after mild AKI followed by kidney architecture restoration, whereas sustained increase in UAGT accompanies by ongoing renal fibrosis after severe AKI...
September 17, 2018: Clinical Science (1979-)
Kumiko Saitou, Masakuni Tokunaga, Daisuke Yoshino, Naoyoshi Sakitani, Takahiro Maekawa, Youngjae Ryu, Motoshi Nagao, Hideki Nakamoto, Taku Saito, Noriaki Kawanishi, Katsuhiko Suzuki, Toru Ogata, Michiru Makuuchi, Atsushi Takashima, Keisuke Sawada, Shunsuke Kawamura, Koichi Nakazato, Karina Kouzaki, Ichiro Harada, Yoshinori Ichihara, Yasuhiro Sawada
Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to ageing. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary life style, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy...
September 12, 2018: Clinical Science (1979-)
Jianqing She, Manyun Guo, Hongbing Li, Junhui Liu, Xiao Liang, Peining Liu, Bo Zhou, Simin Liu, Yangyang Deng, Bowen Lou, Chaofeng Sun, Zuyi Yuan, Yue Wu
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia of which incidence is on the rise globally. However, the pathophysiologic mechanism of AF remains poorly understood, and there has been a lack of circulatory markers to diagnose and predict prognosis of AF. In this study, by measuring metabolic profile and analyzing plasma amino acid levels in AF patients, we sought to determine whether amino acid metabolism was correlated to the occurrence of atrial fibrillation...
September 6, 2018: Clinical Science (1979-)
Benjamin Chatel, Laurent A Messonnier, Christophe Vilmen, Monique Bernard, Vincent Pialoux, David Bendahan
Sickle cell disease (SCD) is characterized by painful vaso-occlusive crises. While there are several metabolic abnormalities potentially associated with muscular ischemia - reperfusion cycles which could be harmful in the context of SCD, the metabolic consequences of such events are still unknown. Ten controls (HbAA), 13 heterozygous (HbAS) and 10 homozygous (HbSS) SCD mice were submitted to a standardized protocol of rest - ischemia - reperfusion of the right leg during which ATP, phosphocreatine and inorganic phosphate concentrations as well as intramuscular pH were measured using phosphorous magnetic resonance spectroscopy (MRS)...
September 5, 2018: Clinical Science (1979-)
Junhui Shen, Zhong-Kai Cui, Fang Yao, Kai Li, Yue Zhang, Zhenguo Chen, Yuxia Zhou, Song Xu, Yuwei Zhang, Wenqing Jiang, Hanbin Zhang, Kaifen Tan, Anling Liu, Xiaochun Bai
Mechanistic target of rapamycin complex 1 (mTORC1) signaling is active in inflammation, but its involvement in septic acute kidney injury (AKI) has not been shown. mTORC1 activation (p-S6) in renal fibroblasts was increased in a mouse AKI model induced by 1.5 mg/kg lipopolysaccharide (LPS). Deletion of TSC1, an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/- ) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice. Endothelin-1 and p-JNK were upregulated in Fibro-TSC1-/- renal fibroblasts after LPS challenge...
September 5, 2018: Clinical Science (1979-)
Lúcio R Requião-Moura, Ana C C Matos, Kikumi S Ozaki, Niels O S Câmara, Alvaro Pacheco-Silva
The indirect effects of cytomegalovirus (CMV) viremia can be related to chronic changes in renal allograft structure, but its real impact in early and late graft function remains speculative. A total of 159 patients undergoing renal transplantation using a preemptive therapeutic strategy to prevent CMV disease were included. The patients were prospectively followed, with serial measurements of urinary retinol-binding protein (uRBP). uRBP levels and their dynamic performance were compared according to CMV viremia and the 5-year estimated glomerular filtration rate (eGFR)...
August 31, 2018: Clinical Science (1979-)
Alexa S Hendricks, Hossam A Shaltout, Brian M Westwood, Mark C Chappell, Debra I Diz
Antenatal betamethasone (BM) therapy for women in jeopardy of premature delivery accelerates the lung development in preterm infants and reduces infant mortality rates, but may induce early programming events with chronic cardiovascular consequences. In a sheep model of fetal programming, in utero BM-exposed (BMX) offspring as adults exhibit elevated mean arterial pressure (MAP), decreased baroreflex sensitivity (BRS) for control of heart rate and insulin resistance accompanied by dysregulation of the brain renin-angiotensin system (RAS)...
July 19, 2018: Clinical Science (1979-)
Chuan Chuan Ren, Qing Wei Wang, Yu Tao Lu, Yan Wang, Wen Zhu, Guo Xian Zhang, Jia Feng Xie, Tao Zhang, Jun Wei Wu, Zhi Ming Jia, Zhi Qiang Su, Jian Guo Wen
Congenital urinary tract obstruction is one of the most frequent malformations in fetuses or neonates which usually causes profound impairment of renal function including reductions in both glomerular filtration rate (GFR) and tubular handling of water and solutes. Although obstruction can be released by surgical operation, the child will suffer from diuresis for some time. It has been reported that erythropoietin (EPO) could prevent the down-regulation of aquaporin-2 (AQP2) and urinary-concentrating defects induced by renal ischemia/reperfusion (I/R) injury...
June 29, 2018: Clinical Science (1979-)
Katharine G Harris, Eugene B Chang
Inflammatory bowel diseases (IBD) are a group of chronic diseases of increasing worldwide prevalence characterized by gastrointestinal (GI) inflammation leading to debilitating symptoms and complications. The contribution of the intestinal microbiota to the pathogenesis and etiology of these diseases is an area of active research interest. Here, we discuss key mechanisms underlying the chronic inflammation seen in IBD as well as evidence implicating the intestinal microbiota in the development and potentiation of that inflammation...
September 28, 2018: Clinical Science (1979-)
Giulia Ferrannini, Lars Rydén
Cardiovascular (CV) disease (CVD) is the main cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Despite optimal glycaemic control, standard antihyperglycaemic therapy failed to impact CV events in intervention trials; therefore, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) issued a guidance to the pharmaceutical industry to specifically assess the CV outcomes and safety of new glucose-lowering drugs. Amongst them, sodium-glucose transporter 2 (SGLT2) inhibitors proved to not only provide good tolerance, few adverse effects, and good glycometabolic control, but also striking reduction in the risk of CV events...
September 28, 2018: Clinical Science (1979-)
Shayna Sharma, Mona Alharbi, Miharu Kobayashi, Andrew Lai, Dominic Guanzon, Felipe Zuñiga, Valeska Ormazabal, Carlos Palma, Katherin Scholz-Romero, Gregory E Rice, John D Hooper, Carlos Salomon
Ovarian cancer has resulted in over 140 000 deaths reported annually worldwide. This is often attributed to cellular changes in the microenvironment, including increased migration of mesenchymal stem cells (MSCs) and endothelial cells (ECs) to facilitate metastasis. Recently, the ability of exosomes to communicate signals between cells (and promote cancer progression) has been established. In the present study, we explored the effect of exosomes on cells present in the tumour microenvironment. Exosomes were isolated from ovarian cancer cells with different invasive capacity (high = SKOV-3 and low = OVCAR-3) by differential and buoyant density centrifugation and characterised using nanoparticle tracking analysis (NTA), Western blot, and EM...
September 28, 2018: Clinical Science (1979-)
Jwu-Lai Yeh, Jiunn-Ren Wu, Bin-Nan Wu, Sheau-Fang Yang, Zen-Kong Dai, Shu-Fen Liou, Jong-Hau Hsu
The physiologic process of postnatal ductus arteriosus (DA) closure consists of vasoconstriction followed by vascular remodeling. We have recently reported that B-type natriuretic peptide (BNP), a potent vasodilator, also has anti-remodeling effects in pulmonary vasculature. However, its effects on DA have not been elucidated. We investigated whether BNP can prevent DA closure, and if so, the underlying mechanisms. Using in vivo studies, we examined effects of BNP (10 mg/kg, ip at birth) on DA closure in neonatal rats within 4 h after birth...
September 28, 2018: Clinical Science (1979-)
Emily N Williams, Keisa W Mathis
The roles of the kidney are well defined, if there is a progressive loss in renal function, the kidney is no longer able to perform the listed tasks and chronic kidney disease (CKD) persists. In both clinical and experimental studies, NaHCO3 supplementation has been shown to improve glomerular filtration rate (GFR) as well as halt the progression toward end-stage renal disease (ESRD). In an article recently published in Clinical Science (vol 132 (11) 1179-1197), Ray et al. presented an intriguing and timely study, which investigates the mechanisms involved in the protection that follows oral NaHCO3 ingestion...
September 14, 2018: Clinical Science (1979-)
Jakob Voelkl, Florian Lang
Systemic acid-base balance is tightly controlled within a narrow range of pH. Disturbances in systemic acid-base homeostasis are associated with diverse detrimental effects. The kidney is a key regulator of acid-base balance, capable of excreting HCO3 - or H+ , and chronic kidney disease invariably leads to acidosis. However, the regulatory pathways underlying the fine-tuned acid-base sensing and regulatory mechanisms are still incompletely understood. In the article published recently in Clinical Science (vol 132 (16) 1779-1796), Poulson and colleagues investigated the role of adenylyl cyclase 6 (AC6) in acid-base homeostasis...
September 14, 2018: Clinical Science (1979-)
Meg L McFetridge, Mark P Del Borgo, Marie-Isabel Aguilar, Sharon D Ricardo
Chronic kidney disease (CKD) is a major and growing public health concern with increasing incidence and prevalence worldwide. The therapeutic potential of stem cell therapy, including mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) holds great promise for treatment of CKD. However, there are significant bottlenecks in the clinical translation due to the reduced number of transplanted cells and the duration of their presence at the site of tissue damage. Bioengineered hydrogels may provide a route of cell delivery to enhance treatment efficacy and optimise the targeting effectiveness while minimising any loss of cell function...
September 14, 2018: Clinical Science (1979-)
Jennifer Kurz, Robert Brunkhorst, Christian Foerch, Leonard Blum, Marina Henke, Laureen Gabriel, Thomas Ulshöfer, Nerea Ferreirós, Michael J Parnham, Gerd Geisslinger, Susanne Schiffmann
Ceramide synthases (CerS) synthesize chain length specific ceramides (Cer), which mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that the genetic deletion of CerS2 suppresses EAE pathology by interaction with granulocyte-colony stimulating factor (G-CSF) signaling and CXC motif chemokine receptor 2 (CXCR2) expression, leading to impaired neutrophil migration. In the present study, we investigated the importance of Cers and their synthesizing/metabolizing enzymes in MS...
September 14, 2018: Clinical Science (1979-)
Michael H Chiu, Bobak Heydari, Zarah Batulan, Nadia Maarouf, Vinita Subramanya, Karin Schenck-Gustafsson, Edward R O'Brien
The recognition of sex differences in cardiovascular disease, particularly the manifestations of coronary artery disease (CAD) in post-menopausal women, has introduced new challenges in not only understanding disease mechanisms but also identifying appropriate clinical means of assessing the efficacy of management strategies. For example, the majority of treatment algorithms for CAD are derived from the study of males, focus on epicardial stenoses, and inadequately account for the small intramyocardial vessel disease in women...
September 14, 2018: Clinical Science (1979-)
Claire E Gustafson, Cornelia M Weyand, Jörg J Goronzy
By 2050, there will be over 1.6 billion adults aged 65 years and older, making age-related diseases and conditions a growing public health concern. One of the leading causes of death in the ageing population is pathogenic infections (e.g. influenza, Streptococcus pneumoniae ). This age-dependent susceptibility to infection has been linked to a reduced ability of the ageing immune system to mount protective responses against infectious pathogens, as well as to vaccines against these pathogens. The primary immune response that promotes protection is the production of antibodies by B cells - a response that is directly mediated by T follicular helper (TFH ) cells within germinal centers (GCs) in secondary lymphoid tissues...
September 14, 2018: Clinical Science (1979-)
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