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Fangwei Li, Wenhua Shi, Yixin Wan, Qingting Wang, Wei Feng, Xin Yan, Jian Wang, Limin Chai, Qianqian Zhang, Manxiang Li
The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat. Identification of target genes for miR-140-5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR-140-5p to provide theoretical evidences for further researches on role of miR-140-5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR-140-5p were predicted in the analysis...
December 2017: FEBS Open Bio
Tom C M Seegar, Lauren B Killingsworth, Nayanendu Saha, Peter A Meyer, Dhabaleswar Patra, Brandon Zimmerman, Peter W Janes, Eric Rubinstein, Dimitar B Nikolov, Georgios Skiniotis, Andrew C Kruse, Stephen C Blacklow
Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated...
November 30, 2017: Cell
Jianlin Qiao, Qi Luo, Na Liu, Guangyu Wei, Xiaoqing Wu, Jun Lu, Kai Tang, Yulu Wu, Jie Zi, Xiaoqian Li, Yun Liu, Wen Ju, Kunming Qi, Zhiling Yan, Zhenyu Li, Lingyu Zeng, Kailin Xu
Immune thrombocytopenia (ITP) is an autoimmune disease, which is characterized by abnormal of T immunity. A disintegrin and metalloproteinase (ADAM) 10, a member of proteinase family, has been demonstrated to regulate T cell proliferation and effector function. Considering the closely association of dysregulation of T cell function with ITP, whether ADAM10 involves in the pathogenesis of ITP remains unclear. In this study, 54 active ITP patients, 18 ITP in remission and 24 age and gender matched healthy control were enrolled...
December 7, 2017: International Immunopharmacology
David Lagares, Parisa Ghassemi-Kakroodi, Caroline Tremblay, Alba Santos, Clemens K Probst, Alicia Franklin, Daniela M Santos, Paula Grasberger, Neil Ahluwalia, Sydney B Montesi, Barry S Shea, Katharine E Black, Rachel Knipe, Meryem Blati, Murray Baron, Brian Wu, Hassan Fahmi, Rajiv Gandhi, Annie Pardo, Moisés Selman, Jiangping Wu, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Andrew M Tager, Mohit Kapoor
This corrects the article DOI: 10.1038/nm.4419.
December 7, 2017: Nature Medicine
Yi Zhang, Lili Tang
Background: Recent studies showed that long non-coding RNA (lncRNA) plays an important role in many life activities. RPPH1 is one of the lncRNA genes that are expressed differently between breast cancer and normal tissues by the lncRNA gene chip. Our study was conducted to examine the regulation of lncRNA RPPH1 in breast cancer. Methods: Two cell lines, MCF-7 and MDA-MB-231, were selected to be the research objects in this study; RPPH1 overexpression and knockdown models were established by transforming vectors...
2017: Cancer Cell International
Toshie Yoneyama, Michael Gorry, Miles A Miller, Autumn Gaither-Davis, Yan Lin, Marcia L Moss, Linda G Griffith, Douglas A Lauffenburger, Laura P Stabile, James G Herman, Nikola L Vujanovic
Increases in expression of ADAM10 and ADAM17 genes and proteins have been evaluated, but not validated as cancer biomarkers. Specific enzyme activities better reflect enzyme cellular functions, and might be better biomarkers than enzyme genes or proteins. However, no high throughput assay is available to test this possibility. Recent studies have developed the high throughput real-time proteolytic activity matrix analysis (PrAMA) that integrates the enzymatic processing of multiple enzyme substrates with mathematical-modeling computation...
2017: Journal of Cancer
Giulia Boccalini, Chiara Sassoli, Daniele Bani, Silvia Nistri
ADAM10 metalloprotease is required for activation of Notch-1, a transmembrane receptor regulating cell differentiation, proliferation and apoptosis, whose intracellular proteolytic fragment NICD mediates some key cardiovascular effects of the hormone relaxin (RLX). This study demonstrates the involvement of ADAM10 and PI3K/Akt signaling in mediating RLX-induced Notch-1 activation. H9c2 cardiomyocytes and NIH3T3 fibroblasts were incubated with human RLX-2 (17 nmol/l, 24 h) in presence or absence of the PI3K or Akt inhibitors wortmannin (WT, 100 nmol/l) and triciribine (TCN, 1 μmol/l)...
November 24, 2017: Molecular and Cellular Endocrinology
Erdinç Dursun, Duygu Gezen-Ak
Our recent study indicated that vitamin D and its receptors are important parts of the amyloid processing pathway in neurons. Yet the role of vitamin D receptor (VDR) in amyloid pathogenesis is complex and all regulations over the production of amyloid beta cannot be explained solely with the transcriptional regulatory properties of VDR. Given that we hypothesized that VDR might exist on the neuronal plasma membrane in close proximity with amyloid precursor protein (APP) and secretase complexes. The present study primarily focused on the localization of VDR in neurons and its interaction with amyloid pathology-related proteins...
2017: PloS One
Xi Kuang, Hong-Jing Zhou, Amy H Thorne, Xi-Nan Chen, Lin-Jiao Li, Jun-Rong Du
Emerging evidence suggests that alpha-processing single transmembrane proteins, amyloid precursor protein (APP) and anti-aging protein Klotho, are likely to be involved in the progression of Alzheimer's disease (AD). The natural phthalide Ligustilide (LIG) has been demonstrated to protect against aging- and amyloid-β (Aβ)-induced brain dysfunction in animal models. The present study is to investigate the effects of LIG on cognitive deficits and metabolism of both APP and Klotho and its underlying mechanism in AD double-transgenic (APP/PS1) mice and cultured human cells...
2017: Frontiers in Aging Neuroscience
Xiancai Ge, Haiyan Cui, Yanbing Zhou, Deying Yin, Yuanyuan Feng, Qun Xin, Xianhui Xu, Weijing Liu, Shanglong Liu, Qin Zhang
MicroRNAs (miRNAs) may function as tumor suppressor or onco‑miRNAs and have critical roles in the pathogenesis of gastric cancer (GC). The exact function and mechanism of miRNA (miR)‑320a in GC remains to be elucidated. The present study performed gain‑ and loss‑of‑function analyses by transfecting cells with mimics or inhibitors and subsequently performing colony formation, proliferation and cisplatin‑sensitivity assays. Additionally, in vivo xenograft models were also performed. Bioinformatics algorithms, luciferase reporter activity assay and western blotting were used to predict the potential target of miR‑320a...
October 19, 2017: Molecular Medicine Reports
Sylwia Kabacik, Ken Raj
The association between ionising radiation (IR) exposure and risk of cardiovascular diseases (CVD) is well documented, but the underlying mechanism is still poorly understood. As atherosclerotic plaques are the most common cause of CVD, we investigated the effects of IR on one of the critical parameters for atherosclerotic plaque formation - endothelium permeability to macromolecules. We used endothelial cells from human coronary artery as a model of the endothelial layer. Our results show that exposure of this endothelial layer to IR increased its permeability to macromolecules of various sizes in a dose-dependent manner...
October 10, 2017: Oncotarget
Kalliopi I Pappa, Georgia Kontostathi, Manousos Makridakis, Vasiliki Lygirou, Jerome Zoidakis, George Daskalakis, Nicholas P Anagnou
BACKGROUND: Oncogenic infection by HPV, eventually leads to cervical carcinogenesis, associated by deregulation of specific pathways and protein expression at the intracellular and secretome level. Thus, secretome analysis can elucidate the biological mechanisms contributing to cervical cancer. In the present study we systematically analyzed its constitution in four cervical cell lines employing a highly sensitive proteomic technology coupled with bioinformatics analysis. MATERIALS AND METHODS: LC/MS-MS proteomics and bioinformatics analysis were performed in the secretome of four informative cervical cell lines SiHa (HPV16(+)), HeLa (HPV18(+)), C33A (HPV(-)) and HCK1T (normal)...
November 2017: Cancer Genomics & Proteomics
Won Seok Yang, Soo Young Moon, Mee Jeong Lee, Eun Kyoung Lee, Su-Kil Park
BACKGROUND/AIMS: We investigated how diosgenin, a steroidal sapogenin, has anti-tumor necrosis factor-α (TNF-α) effects in human aortic endothelial cells (HAECs). METHODS: Tumor necrosis factor receptor 1 (TNFR1) was assessed by Western blot analysis. Intracellular Ca2+ was measured using Fluo-4 AM. Immunofluorescence staining was performed for a disintegrin and metalloprotease 10 (ADAM10). RESULTS: Diosgenin (1 ∼ 100 nM) induced ectodomain shedding of TNFR1 within 30 min and attenuated TNF-α-induced intercellular adhesion molecule-1 (ICAM-1) expression...
October 27, 2017: Cellular Physiology and Biochemistry
Claude-Henry Volmar, Hasib Salah-Uddin, Karolina J Janczura, Paul Halley, Guerline Lambert, Andrew Wodrich, Sivan Manoah, Nidhi H Patel, Gregory C Sartor, Neil Mehta, Nancy T H Miles, Sachi Desse, David Dorcius, Michael D Cameron, Shaun P Brothers, Claes Wahlestedt
Alzheimer's disease (AD) comprises multifactorial ailments for which current therapeutic strategies remain insufficient to broadly address the underlying pathophysiology. Epigenetic gene regulation relies upon multifactorial processes that regulate multiple gene and protein pathways, including those involved in AD. We therefore took an epigenetic approach where a single drug would simultaneously affect the expression of a number of defined AD-related targets. We show that the small-molecule histone deacetylase inhibitor M344 reduces beta-amyloid (Aβ), reduces tau Ser396 phosphorylation, and decreases both β-secretase (BACE) and APOEε4 gene expression...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
Xiaoou Li, Wei Huang, Bing He, Lirong Zhou, Xiaogang Huang, Baozhen Yao
The present study aimed to investigate the roles of the hydrolytic process of N-cadherin by A disintegrin and metalloproteases 10 (ADAM10) in sustaining myocardial structure and integrity, and discuss the mechanisms of ventricular remodeling in dilated cardiomyopathy (DCM). Single chain variable fragment antibody (ScFv) with the ability to specifically block the ADAM10 hydrolysis site of N-cadherin was designed and constructed. Western blot analysis and flow cytometry were used to detect the expression of N-cadherin and its C-terminal fragment 1 (CTF1) on cardiomyocytes, and cells were also subjected to a cell adhesion assay...
November 2017: Experimental and Therapeutic Medicine
David Lagares, Parisa Ghassemi-Kakroodi, Caroline Tremblay, Alba Santos, Clemens K Probst, Alicia Franklin, Daniela M Santos, Paula Grasberger, Neil Ahluwalia, Sydney B Montesi, Barry S Shea, Katharine E Black, Rachel Knipe, Meryem Blati, Murray Baron, Brian Wu, Hassan Fahmi, Rajiv Gandhi, Annie Pardo, Moisés Selman, Jiangping Wu, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Andrew M Tager, Mohit Kapoor
Maladaptive wound healing responses to chronic tissue injury result in organ fibrosis. Fibrosis, which entails excessive extracellular matrix (ECM) deposition and tissue remodeling by activated myofibroblasts, leads to loss of proper tissue architecture and organ function; however, the molecular mediators of myofibroblast activation have yet to be fully identified. Here we identify soluble ephrin-B2 (sEphrin-B2) as a new profibrotic mediator in lung and skin fibrosis. We provide molecular, functional and translational evidence that the ectodomain of membrane-bound ephrin-B2 is shed from fibroblasts into the alveolar airspace after lung injury...
October 23, 2017: Nature Medicine
Jun Arai, Kaku Goto, Anthony Stephanou, Yasushi Tanoue, Sayaka Ito, Ryosuke Muroyama, Yasuo Matsubara, Ryo Nakagawa, Sayuri Morimoto, Yoshimi Kaise, Lay Ahyoung Lim, Hitoshi Yoshida, Naoya Kato
BACKGROUND AND AIM: The multi-kinase inhibitor regorafenib (REG) was recently demonstrated to be effective in patients with sorafenib (SOR)-resistant hepatocellular carcinoma (HCC). Interestingly, SOR is known to enhance the accumulation of membrane-bound MHC class I polypeptide-related sequence A (mMICA) in HCC cells, and to block production of soluble MICA (sMICA), an immunological decoy. In addition, MICA is associated with HCC in patients with chronic hepatitis C. We have now compared the impact of REG and SOR on MICA in HCC cells, as well as the immunotherapeutic implications thereof...
October 21, 2017: Journal of Gastroenterology and Hepatology
Shengxian Shen, Yao Ke, Erle Dang, Hui Fang, Yuqian Chang, Jieyu Zhang, Zhenlai Zhu, Shuai Shao, Pei Qiao, Tongmei Zhang, Hongjiang Qiao, Gang Wang
Autoreactive B cells activation and antibody production are critical events for the development of bullous pemphigoid (BP). However, the mechanism that is involved in the modulation of B cell activation and autoantibody generation has not been fully understood. Semaphorin 4D (Sema4D/CD100) plays important roles in immune regulation related to B cell, but its implication in BP remains obscure. The aim of our study was to characterize Sema4D and the underlying mechanism contributing to the autoimmune features of BP...
October 17, 2017: Journal of Investigative Dermatology
Jeongyeon Park, Jong Hwa Kwon, Nam Kim, Kiwon Song
Alzheimer's disease (AD) is a neurodegenerative disease leading to progressive loss of memory and other cognitive functions. One of the well-known pathological markers of AD is the accumulation of amyloid-beta protein (Aβ), and its plaques, in the brain. Recent studies using Tg-5XFAD mice as a model of AD have reported that exposure to radiofrequency electromagnetic fields (RF-EMF) from cellular phones reduced Aβ plaques in the brain and showed beneficial effects on AD. In this study, we examined whether exposure to 1950 MHz RF-EMF affects Aβ processing in neural cells...
October 6, 2017: Journal of Radiation Research
Kyung In Baek, René R Sevag Packard, Jeffrey J Hsu, Arian Saffari, Zhao Ma, Anh Phuong Luu, Andrew Pietersen, Hilary Yen, Bin Ren, Yichen Ding, Constantinos Sioutas, Rongsong Li, Tzung K Hsiai
AIMS: Redox active ultrafine particles (UFP, d < 0.2 μm) promote vascular oxidative stress and atherosclerosis. Notch signaling is intimately involved in vascular homeostasis, in which forkhead box O1 (FOXO1) acts as a co-activator of the Notch activation complex. We elucidated the importance of FOXO1/Notch transcriptional activation complex to restore vascular regeneration after UFP exposure. RESULTS: In a zebrafish model of tail injury and repair, transgenic Tg(fli1:GFP) embryos developed vascular regeneration at 3 days post amputation (dpa), whereas UFP exposure impaired regeneration (p < 0...
November 17, 2017: Antioxidants & Redox Signaling
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