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Clinical Science (1979-)

Vidya K Nagalakshmi, Minghong Li, Soham Shah, Joseph C Gigliotti, Alexander L Klibanov, Frederick H Epstein, Robert L Chevalier, R Ariel Gomez, Maria Luisa Soledad Sequeira Lopez
Congenital obstructive nephropathy is a major cause of chronic kidney disease in children. The contribution of changes in the identity of renal cells to the pathology of obstructive nephropathy is poorly understood. Using a partial unilateral ureteral obstruction model in genetically modified neonatal mice, we traced the fate of cells derived from the renal stroma, cap mesenchyme, ureteric bud epithelium and podocytes using Foxd1Cre , Six2Cre , HoxB7Cre and Podocyte.Cre mice respectively, crossed with double fluorescent reporter (mT/mG) mice...
November 15, 2018: Clinical Science (1979-)
Kamal Jafarian, Kamran Hassani, D John Doyle, Mohammad Niakan Lahiji, Omid Moradi Moghaddam, Ala Saket, Mahsa Majidi, Farhad Izadi
The need for simple and reliable means of respiratory monitoring has existed since the beginnings of medicine. In this study we describe the use of color spectrographic analysis of breathing sounds recorded from the external ear canal as a candidate technology to meet this need. A miniature electret microphone was modified with the addition of an adapter to allow it to be placed comfortably in the external ear canal. The amplified signal was then connected to a real-time color spectrogram program running on a laptop personal computer utilizing the Windows operating system...
November 12, 2018: Clinical Science (1979-)
Yuki Sato, Rena Watanabe, Nozomi Uchiyama, Nana Ozawa, Yui Takahashi, Remina Shirai, Kengo Sato, Yusaku Mori, Taka-Aki Matsuyama, Hatsue Ishibashi-Ueda, Tsutomu Hirano, Takuya Watanabe
Vasostatin-1,a chromogranin A-derived peptide (76 amino acids),is known to suppress vasoconstriction and angiogenesis.A recent study has shown that vasostatin-1 suppresses the adhesion of human U937 monocytes to human endothelial cells (HECs) via adhesion molecule downregulation. The present study evaluated the expression of vasostatin-1 in human atherosclerotic lesionsand its effects on inflammatory responses in HECs and human THP-1 monocyte-derived macrophages,macrophagefoam cell formation, migration and proliferation of human aortic smooth muscle cells (HASMCs) and extracellular matrix production by HASMCs, and atherogenesisin apolipoprotein E-deficient (ApoE-/- ) mice...
November 6, 2018: Clinical Science (1979-)
Gargi Mahapatra, S Carrie Smith, Timothy M Hughes, Benjamin Wagner, Joseph A Maldjian, Barry I Freedman, Anthony J A Molina
Blood-based bioenergetic profiling has promising applications as a minimally invasive biomarker of systemic bioenergetic capacity. In this study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with longstanding Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes.  Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology...
November 6, 2018: Clinical Science (1979-)
Jasmin Strutz, Silvija Cvitic, Hubert Hackl, Karl Kashofer, Hannah Magdalena Appel, Andrea Thüringer, Gernot Desoye, Pieter Koolwijk, Ursula Hiden
MicroRNAs (miRNAs), small non-coding RNAs, have emerged as important, epigenetic regulators of endothelial function. Metabolic disturbances such as diabetes alter miRNA expression. In adults the miRNA transcriptome as well as endothelial function differ between the sexes. Here we hypothesized that metabolic disturbances associated with gestational diabetes (GDM) alter miRNA signatures in feto-placental endothelial cells (fpEC), dependent on fetal sex. We isolated human primary fpEC after normal and GDM-complicated pregnancies with male and female neonates and screened for differential miRNA expression using next generation miRNA sequencing...
November 2, 2018: Clinical Science (1979-)
Alessandra Magenta, Sara Sileno, Marco D'Agostino, Francesca Persiani, Sara Beji, Alessandra Paolini, Daniele Camilli, Alessandro Platone, Maurizio C Capogrossi, Sergio Furgiuele
Early recognition of vulnerable carotid plaques could help identifying patients at high stroke risk, who may benefit of earlier revascularization. Nowadays, different biomarkers of plaque instability have been unravelled, among these microRNAs are promising tools for the diagnosis and treatment of atherosclerosis. Inflammation, reactive oxygen species (ROS) and endothelial dysfunction play a key role in unstable plaques genesis. We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two microRNAs involved in atherosclerosis progression...
November 2, 2018: Clinical Science (1979-)
Floor Spaans, Anita Quon, Stewart R Rowe, Jude S Morton, Raven Kirschenman, Tatsuya Sawamura, Dionne S Tannetta, Ian L Sargent, Sandra T Davidge
Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function, however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via LOX-1, a multi-ligand scavenger receptor that has been associated with vascular dysfunction. Recently, LOX-1 was shown to interact with the AT-1 receptor for angiotensin II. We hypothesized that, in pregnant mice, STBEVs would impair vascular function via LOX-1 and would specifically affect angiotensin II responses...
October 23, 2018: Clinical Science (1979-)
I-Fang Hsin, Hui-Chun Huang, Ching-Chih Chang, Shao-Jung Hsu, Fa-Yauh Lee, Teh-Ia Huo, Chiao-Lin Chuang, Ming-Chih Hou, Shou-Dong Lee
Liver cirrhosis is accompanied by increased intrahepatic resistance and angiogenesis-related portosystemic collaterals formation. Diabetic patients suffer from abnormal vasoresponsiveness and angiogenesis that can be ameliorated by glucose control. However, the relevant presentation is not clear in those with cirrhosis and diabetes, in whom insulin is the treatment of choice. Liver cirrhosis was induced in Sprague-Dawley rats with bile duct ligation (BDL) and sham rats were used as controls. Streptozotocin 60 mg/kg (STZ, i...
October 22, 2018: Clinical Science (1979-)
Wenxia Yang, Ying Luo, Shikun Yang, Mengru Zeng, Shumin Zhang, Jialu Liu, Yuzhang Han, Yu Liu, Xuejing Zhu, Hao Wu, Fuyou Liu, Lin Sun, Li Xiao
Emerging studies suggest that lipid accumulates in the kidneys during diabetic kidney disease (DKD). However, the correlation between ectopic lipid accumulation with tubular damage has not been thoroughly elucidated to date. Using Oil Red staining, lipid accumulation was observed in the kidneys of type 2 DKD patients (class II-III) and db/db mice compared to the control and was predominantly located in the proximal tubular compartment. Immunohistochemistry staining showed that the intensity of adipose differentiation related protein (ADRP) and sterol-regulatory element binding protein-1 (SREBP-1) was clearly upregulated, which was positively correlated with the tubulointerstitial damage score and inflammation...
October 22, 2018: Clinical Science (1979-)
Binbin Li, Liwei Yu, Dong Liu, Xueyan Yang, Yufang Zheng, Yonghao Gui, Hongyan Wang
Congenital heart disease (CHD) is one of the most common birth defects in humans, but its genetic etiology remains largely unknown despite decades of research. The Notch signaling pathway plays critical roles in embryonic cardiogenesis. Mind bomb 1 (Mib1) is a vital protein that activates the Notch signaling pathway through promoting ubiquitination, endocytosis and subsequent activation of Notch ligands. Previous studies show that Mib1 knockout in mice completely abolishes Notch signaling, leading to cardiac deformity...
October 15, 2018: Clinical Science (1979-)
Zhenzhen Li, Xianghua Liu, Fengyan Tian, Ji Li, Qingwei Wang, Chaohui Gu
Epithelial-to-mesenchymal transition (EMT) is a phenotypic conversion that plays a crucial role in renal fibrosis leading to chronic renal failure. Mitogen-activated protein kinase phosphatase 2 (MKP2) is a member of the dual-specificity MKPs that regulate the MAP kinase pathway involved in transforming growth factor-β1(TGF-β1)-induced EMT. However, the function of MKP2 in the regulation of EMT and the underlying mechanisms are still largely unknown. In the present study, we detected the expression of MKP2 in an animal model of renal fibrosis and evaluated the potential role of MKP2 in tubular EMT induced by TGF-β1...
October 15, 2018: Clinical Science (1979-)
Reiko Sakurai, Jie Liu, Ying Wang, John S Torday, Virender K Rehan
Perinatal nicotine exposure drives the differentiation of alveolar lipofibroblasts (LIFs), which are critical for lung injury repair, to myofibroblasts (MYFs), which are the hallmark of chronic lung disease. Bone marrow-derived mesenchymal stem cells (BMSCs) are important players in lung injury repair; however, how these cells are affected with perinatal nicotine exposure and whether these can be preferentially driven to a lipofibroblastic phenotype are not known. We hypothesized that perinatal nicotine exposure would block offspring BMSCs lipogenic differentiation, driving these cells towards a MYF phenotype...
October 11, 2018: Clinical Science (1979-)
Ping Chen, De-Qiang Xu, Sheng-Li Xu, He Xiao, Sheng-Hong Wan, Xing-Huan Wang, Michael E DiSanto, Xin-Hua Zhang
OBJECTIVES: To investigate the effect of blebbistatin (BLEB, a selective myosin inhibitor) on regulating contractility and growth of prostate cells and to provide insight into possible mechanisms associated with these actions. METHODS: BLEB was incubated with cell lines of BPH-1 and WPMY-1 and was intra-prostatically injected into rats. Cell growth was determined by flow cytometry and in vitro organ bath studies were performed to explore smooth muscle (SM) contractility...
October 2, 2018: Clinical Science (1979-)
Soumyalekshmi Nair, Nanthini Jayabalan, Dominic Guanzon, Carlos Palma, Katherin Scholz-Romero, Omar Elfeky, Felipe Zuñiga, Valeska Ormazabal, Emilio Diaz, Gregory E Rice, Gregory Duncombe, Thomas Jansson, Harold David McIntyre, Martha Lappas, Carlos Salomon
There is increasing evidence that miRNAs, which are enriched in nanovesicles called exosomes, are important regulators of gene expression. When compared to normal pregnancies, gestational diabetes mellitus (GDM) is associated with skeletal muscle insulin resistance as well as increased levels of circulating placental exosomes. Here we investigated whether placental exosomes in GDM carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Exosomes were isolated from chorionic villous (CV) explants from both women with Normal Glucose Tolerant (NGT) and GDM pregnancies...
September 25, 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-)
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-)
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-)
Katie L Connor, Laura Denby
Accurate biomarkers that both predict the progression to, and detect the early stages of chronic kidney disease (CKD) are lacking, resulting in difficulty in identifying individuals who could potentially benefit from targeted intervention. In a recent issue [ Clinical Science (2018) 132 , 2121-2133], Cui et al. examine the ability of urinary angiotensinogen (uAGT) to predict the progression of acute kidney injury (AKI) to CKD. They principally employ a murine ischaemia reperfusion injury model to study this and provide data from a small prospective study of patients with biopsy proven acute tubular necrosis...
November 15, 2018: Clinical Science (1979-)
Phuc N H Trinh, Lauren T May, Katie Leach, Karen J Gregory
Metabotropic glutamate receptors belong to class C G-protein-coupled receptors and consist of eight subtypes that are ubiquitously expressed throughout the central nervous system. In recent years, the metabotropic glutamate receptor subtype 5 (mGlu5 ) has emerged as a promising target for a broad range of psychiatric and neurological disorders. Drug discovery programs targetting mGlu5 are primarily focused on development of allosteric modulators that interact with sites distinct from the endogenous agonist glutamate...
November 15, 2018: Clinical Science (1979-)
Jinfang Bao, Yingfeng Shi, Min Tao, Na Liu, Shougang Zhuang, Weijie Yuan
Autophagy has been identified as a cellular process of bulk degradation of cytoplasmic components and its persistent activation is critically involved in the renal damage induced by ureteral obstruction. However, the role and underlying mechanisms of autophagy in hyperuricemic nephropathy (HN) remain unknown. In the present study, we observed that inhibition of autophagy by 3-methyladenine (3-MA) abolished uric acid-induced differentiation of renal fibroblasts to myofibroblasts and activation of transforming growth factor-β1 (TGF-β1), epidermal growth factor receptor (EGFR), and Wnt signaling pathways in cultured renal interstitial fibroblasts...
November 15, 2018: Clinical Science (1979-)
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