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Clinical Science (1979-)

Qing Yu, Wenxin Kou, Xu Xu, Shunping Zhou, Peipei Luan, Xiaopeng Xu, Hailing Li, Jianhui Zhuang, Jun Wang, Yifan Zhao, Yawei Xu, Wen-Hui Peng
Cardiac hypertrophy is a common pathophysiological process in various cardiovascular diseases, which still has no effective therapies. Irisin is a novel myokine mainly secreted by skeletal muscle and is believed involved in the regulation of energy metabolism. In the present study, we found that irisin expression was elevated in hypertrophic murine hearts and serum. Moreover, angiotension II-induced cardiomyocyte hypertrophy was attenuated after irisin administration and aggravated after irisin knockdown in vitro...
February 19, 2019: Clinical Science (1979-)
Chao Liu, Jiaqi Shi, Qingwei Li, Zhiwei Li, Changjie Lou, Qi Zhao, Yuanyuan Zhu, Fei Zhan, Jie Lian, Bojun Wang, Xin Guan, Lin Fang, Zengxun Li, Yifei Wang, Bodong Zhou, Yuanfei Yao, Yanqiao Zhang
Forkhead box protein M1 (FOXM1) was identified as an oncogenic transcription factor and master regulator of tumor progression and metastasis. FOXM1 expression often correlates with poor prognosis and chemotherapy resistance. In the present study, we investigated the association of FOXM1 expression and chemoresistance in pancreatic cancer. Elevated FOXM1 protein levels were associated with gemcitabine chemoresistance in patients with pancreatic cancer. In gemcitabine resistance cell line models of pancreatic cancer, FOXM1 expression increased, which induced gemcitabine chemoresistance in vitro In pancreatic cancer cells treated with gemcitabine, FOXM1 affected NF-κB signaling activity...
February 19, 2019: Clinical Science (1979-)
Fumiko Nakazeki, Itaru Tsuge, Takahiro Horie, Keiko Imamura, Kayoko Tsukita, Akitsu Hotta, Osamu Baba, Yasuhide Kuwabara, Tomohiro Nishino, Tetsushi Nakao, Masataka Nishiga, Hitoo Nishi, Yasuhiro Nakashima, Yuya Ide, Satoshi Koyama, Masahiro Kimura, Shuhei Tsuji, Motoko Naitoh, Shigehiko Suzuki, Yuishin Izumi, Toshitaka Kawarai, Ryuji Kaji, Takeshi Kimura, Haruhisa Inoue, Koh Ono
Recent reports, including ours, have indicated that microRNA (miR)-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here we show that SPAST , which encodes a microtubule-severing protein called spastin, was a novel target gene of miR-33 in human. Actually, the miR-33 binding site in the SPAST 3'-UTR is conserved not in mice but in mid to large mammals, and it is impossible to clarify the role of miR-33 on SPAST in mice...
February 18, 2019: Clinical Science (1979-)
Fernando Pedro de Souza-Neto, Mario Morais Silva, Melissa de Carvalho Santuchi, Thaís Carvalho de Alcântara-Leonídio, Daisy Motta-Santos, Aline Oliveira, Marcos Barrouin Melo, Giovanni Naves Canta, Leandro Ezequiel de Souza, Maria Claudia Irigoyen, Maria José Campagnole-Santos, Silvia Guatimosim, Robson Augusto Souza Dos Santos, Rafaela Fernandes da Silva
Aims - The renin-angiotensin system (RAS) plays an important role in the pathophysiology of vascular diseases, especially as a mediator of inflammation and tissue remodelling. Alamandine is a new biologically active peptide from the RAS, interacting with Mas-related G-protein-coupled receptor member D. Although a growing number of studies reveal the cardioprotective effects of alamandine, there is a paucity of data on its participation in vascular remodelling associated events. In this study, we investigated the effects of alamandine on ascending aorta remodelling after transverse aortic constriction (TAC) in mice...
February 8, 2019: Clinical Science (1979-)
Xuhua Yu, Huei Jiunn Seow, Hao Wang, Desiree Anthony, Steven Bozinovski, Lin Lin, Ji-Ming Ye, Ross Vlahos
Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiate and drive the long-term progression of disease...
February 7, 2019: Clinical Science (1979-)
Shiquan Chai, Kaixuan Liu, Wanbing Feng, Tiantian Liu, Qian Wang, Rong Zhou, Shiming Chen, Liyan Wang, Guanyu Chen, Tian Ming, Jiandong Zhao, Chuanyong Liu, Bing Xue
The intestinal ischemia/reperfusion (I/R) injury is a common clinical event related with high mortality in patients undergoing surgery or trauma. Estrogen exerts salutary effect on intestinal I/R injury, but the receptor type is not totally understood. We aimed to identify whether the G protein-coupled estrogen receptor (GPER) could protect the intestine against I/R injury and explored the mechanism. Adult male C57BL/6 mice were subjected to intestinal I/R injury by clamping (45 min) of the superior mesenteric artery followed by 4 h of intestinal reperfusion...
January 31, 2019: Clinical Science (1979-)
Chayodom Maneechote, Siripong Palee, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Siriporn Chattipakorn, Nipon Chattipakorn
An uncontrolled balance of mitochondrial dynamics has been shown to contribute to cardiac dysfunction during I/R injury.  Although inhibition of mitochondrial fission could ameliorate cardiac dysfunction, modulation of mitochondrial fusion by giving a fusion promoter at different time-points during cardiac I/R injury has never been investigated.  We hypothesized that giving of a mitochondrial fusion promoter at different time-points exerts cardioprotection with different levels of efficacy in rats with cardiac I/R injury...
January 31, 2019: Clinical Science (1979-)
Jiao Huang, Hua Liu, Tiantian Sun, Jing-Yuan Fang, Jilin Wang, Hua Xiong
Activation of hedgehog(Hh) signaling contributes to the progression of Barrett's Esophagus(BE), which increases the risk of esophageal adenocarcinoma. Recent clinical studies revealed Proton-pump inhibitors (PPIs) but not H2 Receptor Antagonists (H2RAs) were associated with a decreased risk of esophageal adenocarcinoma. We would like to know whether PPIs interfere with BE progression during BE treatment. Here, we explored the role of omeprazole on Hh signaling and expression of two crucial biomarkers of BE, SOX9 and CDX2...
January 31, 2019: Clinical Science (1979-)
Wang-Sheng Wang, Wen-Jiao Li, Ya-Wei Wang, Lu-Yao Wang, Ya-Bing Mi, Jiang-Wen Lu, Yi Lu, Chu-Yue Zhang, Kang Sun
The de novo synthesis of serum amyloid A1 (SAA1) is augmented in human fetal membranes at parturition. However, its role in parturitionremains largely unknown. Here, we investigated whether SAA1 wasinvolved inthe rupture of fetal membranes, a crucial event in parturition accompanied with extensive degradation of collagens. Results showed that SAA1 decreased both intracellular and extracellular COL1A1 and COL1A2 abundance,the two subunits ofcollagen I, without affecting theirmRNAlevels in human amnion fibroblasts...
January 25, 2019: Clinical Science (1979-)
Yinlan Hu, Guoqing Jin, Bing Li, Yanmei Chen, Lintao Lin Zhong, Guojun Chen, Xiaoqing Chen, Jiayuan Zhong, Wangjun Liao, Yulin Liao, Yuegang Wang, Jianping Bin
MicroRNAs regulate the cardiomyocyte cell cycle at the post-transcriptional level, affect cell proliferation and intervene in harmed cardiomyocyte repair post-injury. This study was undertaken to characterize the role of let-7i-5p in the processes of cardiomyocyte cell cycle and proliferation and to reveal the mechanisms thereof. In this study, we used real-time qPCR to determine the upregulated let-7i-5p in cardiomyocytes during the postnatal switch from proliferation to terminal differentiation and further validated the role of let-7i-5p by loss- and gain-of-function of let-7i-5p in cardiomyocytes in vitro and in vivo We found that the overexpression of let-7i-5p inhibited cardiomyocyte proliferation, whereas the suppression of let-7i-5p significantly facilitated cardiomyocyte proliferation...
January 24, 2019: Clinical Science (1979-)
Dan Liu, Peilang Yang, Min Gao, Tianyi Yu, Yan Shi, Meng Zhang, Min Yao, Yan Liu, Xiong Zhang
Persistent inflammatory response in the diabetic wound impairs the healing process, resulting in significant morbidity and mortality. Mounting evidence indicates that the activation of Nod-like receptor protein (NLRP) 3 inflammasome in macrophages (Mϕ) contributes to the sustained inflammatory response and impaired wound healing associated with diabetes. However, the main trigger of NLRP3 inflammasome in the wounds is not known. Neutrophils, as sentinels of the innate immune system and key stimulators of Mϕ, are immune cells that play the main role in the early phase of healing...
January 9, 2019: Clinical Science (1979-)
David C Andrade, Camilo Toledo, Hugo S Díaz, Claudia Lucero, Alexis Arce-Álvarez, Luis M Oliveira, Ana C Takakura, Thiago S Moreira, Harold D Schultz, Noah J Marcus, Julio Alcayaga, Rodrigo Del Rio
Activation of the sympathetic nervous system is ahallmark of heart failure and is positively correlated with disease progression. Catecholaminergic (C1) neurons locatedin the rostral ventrolateral medulla (RVLM) are known to modulate sympathetic outflow and are hyperactivated in volume overload heart failure (HF). However, there is no conclusiveevidence showing acontribution of RVLM-C1 neurons to the developmentof cardiac dysfunctionin the setting of HF. Therefore, the aim of this study was to determine the role of RVLM-C1 neurons in cardiac autonomic control and deterioration of cardiac function in HF rats...
January 9, 2019: Clinical Science (1979-)
Jianjun Jin, Huanqin Wang, Jiming Si, Ran Ni, Yuanhua Liu, Jing Wang
Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small cell lung cancer (NSCLC). ZEB1-AS1 overexpression predicts a poor prognosis in osteosarcoma and colorectal cancers. In the current study, we determined the clinical significance and prognostic value of ZEB1-AS1 in patients with NSCLC. The expression of ZEB1-AS1 and inhibitor of differentiation-1 (ID1) was measured using qRT-PCR and Western blot. Cell growth, migration, and invasion was determined using colony formation assays, Transwell assay, and flow cytometry, respectively...
January 9, 2019: Clinical Science (1979-)
Catalina Atorrasagasti, Agostina Onorato, María Laura Gimeno, Luz Andreone, Mariana Garcia, Mariana Malvicini, Esteban Fiore, Juan Bayo, Marcelo J Perone, Guillermo Mazzolini
Obesity, metabolic syndrome and type 2 diabetes, three strongly interrelated diseases, are associated to increased morbidity and mortality worldwide. The pathogenesis of obesity-associated disorders is still under study. SPARC is a matricellular glycoprotein expressed in many cell types including adipocytes, parenchymal and non-parenchymal hepatic cells and pancreatic cells. Studies have demonstrated that SPARC inhibits adipogenesis and promotes insulin resistance; in addition, circulating SPARC levels were positively correlated with BMI in obese individuals...
January 9, 2019: Clinical Science (1979-)
Jiangqiao Zhou, Tao Qiu, Tianyu Wang, Zhonbao Chen, Xiaoxiong Ma, Long Zhang, Jilin Zou
Ubiquitin-specific peptidase 4 (USP4) protein is a type of deubiquitination enzyme that is correlated with many important biological processes. However, the function of USP4 in hepatic ischaemia/reperfusion (I/R) injury remains unknown. The aim of this study was to explore the role of USP4 in hepatic I/R injury. USP4 gene knockout mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP4 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP4 was significantly upregulated in liver of mice subjected to hepatic I/R injury...
January 8, 2019: Clinical Science (1979-)
Steven J Forrester, Qian Xu, Daniel S Kikuchi, Derick Okwan-Duodu, Ana Carolina Campos, Elizabeth A Faidley, Guogang Zhang, Bernard Lassègue, Ruxana T Sadikot, Kathy K Griendling, Marina S Hernandes
Acute respiratory distress syndrome (ARDS) in a deadly disease that can be brought on by endotoxins such as lipopolysaccharide (LPS). ARDS is characterized by vascular permeability, a severe inflammatory response, lung leukocyte infiltration, and resultant lung edema. Polymerase delta-interacting protein 2 (Poldip2) is a novel regulator of blood-brain barrier permeability; however, its role in regulating lung permeability and vascular inflammation is unknown. Here, the role of Poldip2 in regulating vascular permeability and inflammation in a mouse model of ARDS was assessed...
January 8, 2019: Clinical Science (1979-)
Roel Bijkerk, Marina A Aleksinskaya, Jacques Mgj Duijs, Jennifer Veth, Bettina Husen, Dania Reiche, Cornelia Prehn, Jerzy Adamski, Ton J Rabelink, Jo G R De Mey, Anton Jan van Zonneveld
Kidney fibrosis is the common pathophysiological mechanism in end-stage-renal-disease characterized by excessive accumulation of myofibroblast-derived extracellular matrix. Natriuretic peptides have been demonstrated to have cGMP-dependent anti-fibrotic properties likely due to interference with pro-fibrotic TGF-β signaling. However, in vivo , natriuretic peptides are rapidly degraded by neutral endopeptidases (NEP). In a unilateral urether obstruction (UUO) mouse model for kidney fibrosis we assessed the anti-fibrotic effects of SOL1, an orally-active compound that inhibits NEP and endothelin-converting enzyme (ECE)...
January 7, 2019: Clinical Science (1979-)
Jing Chen, Di Wu, Yue Zhang, Yong Yang, Yunfei Duan, Yong An
Long non-coding RNAs (lncRNAs) play important roles in a variety of tumours; however, their biological function and clinical significance in hepatocellular carcinoma (HCC) are still unclear. In this study, the clinical significance, biological function and regulatory mechanisms of lncRNA DCST1-AS1 in HCC were investigated. Differential lncRNAs in HCC were identified based on The Cancer Genome Atlas (TCGA) database. The biological function and mechanism of DCST1-AS1 were studied in vitro and in vivo. LncRNA DCST1-AS1 was highly expressed in HCC tissues, and the high expression of DCST1-AS1 was significantly correlated with larger tumours and shorter survival time...
January 7, 2019: Clinical Science (1979-)
Mathilde L Bonnemaison, Eileen S Marks-Nelson, Erika I Boesen
Systemic lupus erythematosus (SLE) is an autoimmune disease predominantly affecting women and often leading to lupus nephritis and kidney damage. Endoplasmic reticulum (ER) stress has been implicated in several forms of kidney disease, but whether ER stress contributes to renal injury in SLE is unknown. To investigate this, a small molecule chaperone, sodium 4-phenylbutyrate (4-PBA), was administered to the NZBWF1 mouse model of SLE. In a prevention study, treatment with 4-PBA from 20 weeks of age (prior to the development of renal injury) delayed the onset of albuminuria and significantly reduced additional indices of renal injury compared to vehicle-treated NZBWF1 mice at 36 weeks of age, including collagen deposition, tubular casts, renal cell apoptosis, and blood urea nitrogen concentration (BUN)...
January 7, 2019: Clinical Science (1979-)
Yifang Xie, Anyun Ma, Boshi Wang, Rui Peng, Yingchun Jing, Deqian Wang, Richard H Finnell, Bin Qiao, Yongming Wang, Hongyan Wang, Yufang Zheng
TOF (Tetralogy of Fallot) is the most common cyanotic form of congenital heart defects (CHDs). The right ventricular hypertrophy is associated with the survival rate of patients with repaired TOF. However, very little is known concerning its genetic etiology. Based on mouse model studies, ADAM10 and ADAM17 are the key enzymes for the NOTCH and ErbB pathways, which are critical pathways for heart development. Mutations in these two genes have not been previously reported in human TOF patients. In this study, we sequenced ADAM10 and ADAM17 in a Han Chinese CHD cohort comprised of 80 TOF patients, 286 other CHD patients, and 480 matched healthy controls...
January 4, 2019: Clinical Science (1979-)
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