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Toshiaki Teratani, Kengo Tomita, Takahiro Suzuki, Hirotaka Furuhashi, Rie Irie, Makoto Nishikawa, Junji Yamamoto, Toshifumi Hibi, Soichiro Miura, Tohru Minamino, Yuichi Oike, Ryota Hokari, Takanori Kanai
Incidence of nonalcoholic steatohepatitis (NASH), which is considered a hepatic manifestation of metabolic syndrome, has been increasing worldwide with the rise in obesity; however, its pathological mechanism is poorly understood. Here, we demonstrate that the hepatic expression of aortic carboxypeptidase-like protein (ACLP), a glycosylated, secreted protein, increases in NASH in humans and mice. Furthermore, we elucidate that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology...
March 19, 2018: Journal of Clinical Investigation
Chen Sun, Jianxia Li
PURPOSE: To investigate the expression of microRNA (miRNA-137) in oral squamous cell carcinoma (OSCC) and its effects on activity, invasion and proliferation of OSCC human squamous cell carcinoma cell lines 2 (HSC-2 cell line). METHODS: 158 cases of pathologically-confirmed OSCC tissues and corresponding para-cancerous tissues were collected. The tissue mRNA was extracted and miRNA-137 expression in tissues was detected using real-time polymerase chain reaction (RT-PCR)...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Zhou Zhou, Ming-Jiang Xu, Yan Cai, Wei Wang, Joy X Jiang, Zoltan V Varga, Dechun Feng, Pal Pacher, George Kunos, Natalie J Torok, Bin Gao
Background & Aims: Hepatic infiltration of neutrophils is a hallmark of steatohepatitis; however, the role of neutrophils in the progression of steatohepatitis remains unknown. Methods: A clinically relevant mouse model of steatohepatitis induced by high-fat diet (HFD) plus binge ethanol feeding was used. Liver fibrosis was examined. In vitro cell culture was used to analyze the interaction of hepatic stellate cells (HSCs) and neutrophils. Results: HFD plus one binge ethanol (HFD+1B) feeding induced significant hepatic neutrophil infiltration, liver injury, and fibrosis...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Kentaro Hosokawa, Fumio Arai
In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length...
March 17, 2018: International Journal of Hematology
Ziqiang Li, Li Ji, Shengyan Su, Xiaofei Zhu, Fangyun Cheng, Xin Jia, Qian Zhou, Yajun Zhou
Obese patients, often accompanied by hyperleptinemia, are prone to liver fibrogenesis. Leptin is an adipocyte-derived hormone and plays a promotion role in liver fibrosis. Sterol regulatory element binding protein-1c (SREBP1c) exerts a crucial role in inhibiting hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Our previous studies indicated that leptin inhibited SREBP1c expression, contributing to leptin-induced HSC activation and liver fibrosis. microRNAs (miR) have emerged as important layers of regulatory control and regulate gene expression, and are implicated in numerous diseases...
March 13, 2018: Experimental Cell Research
Benjamin Wildman-Tobriner, Michael S Enslow, Rendon C Nelson
OBJECTIVE: When objectively measured on computed tomography (CT), does hepatic heterogeneity or overall liver attenuation predict the presence of shock? METHODS: This retrospective study included 73 patients (mean age 33 years) with the hypoperfusion shock complex (HSC) on CT (cases) and 100 patients (mean age 43 years) with negative trauma CT scans (controls). Liver heterogeneity was calculated by using consistently sized regions of interest (ROIs) to measure the 2 highest and the 2 lowest areas of hepatic density (in Hounsfield units [HU])...
February 10, 2018: Current Problems in Diagnostic Radiology
Alejandra M Petrilli, Cristina Fernández-Valle
Schwannomas are benign nerve tumors that occur sporadically in the general population and in those with neurofibromatosis type 2 (NF2), a tumor predisposition genetic disorder. NF2-associated schwannomas and most sporadic schwannomas are caused by inactivating mutations in Schwann cells in the neurofibromatosis type 2 gene (NF2) that encodes the merlin tumor suppressor. Despite their benign nature, schwannomas and especially vestibular schwannomas cause considerable morbidity. The primary available therapies are surgery or radiosurgery which usually lead to loss of function of the compromised nerve...
2018: Methods in Molecular Biology
Shiwei Zheng, Efthymia Papalexi, Andrew Butler, William Stephenson, Rahul Satija
Hematopoietic stem cells (HSCs) give rise to diverse cell types in the blood system, yet our molecular understanding of the early trajectories that generate this enormous diversity in humans remains incomplete. Here, we leverage Drop-seq, a massively parallel single-cell RNA sequencing (scRNA-seq) approach, to individually profile 20,000 progenitor cells from human cord blood, without prior enrichment or depletion for individual lineages based on surface markers. Our data reveal a transcriptional compendium of progenitor states in human cord blood, representing four committed lineages downstream from HSC, alongside the transcriptional dynamics underlying fate commitment...
March 15, 2018: Molecular Systems Biology
Alborz Karimzadeh, Vanessa M Scarfone, Erika Varady, Connie Chao, Karin Grathwohl, John W Fathman, David A Fruman, Thomas Serwold, Matthew A Inlay
Hematopoietic stem cells (HSCs) are the self-renewing multipotent progenitors to all blood cell types. Identification and isolation of HSCs for study has depended on the expression of combinations of surface markers on HSCs that reliably distinguish them from other cell types. However, the increasing number of markers required to isolate HSCs has made it tedious, expensive, and difficult for newcomers, suggesting the need for a simpler panel of HSC markers. We previously showed that phenotypic HSCs could be separated based on expression of CD11a and that only the CD11a negative fraction contained true HSCs...
March 15, 2018: Stem Cells Translational Medicine
Qian Li, Jiao Chen, Xiaoying Li, Bomiao Cui, Yaping Fan, Ning Geng, Qianming Chen, Ping Zhang, Yun Feng
High mobility group nucleosomal-binding domain 2 (HMGN2) is an abundant non-histone nuclear protein of vertebrates and invertebrates. The aim of the present study was to characterize the endogenous expression of HMGN2 in various types of tumor cell. Western blotting was performed to analyze HMGN2 expression in the following tumor cell lines: H1975, HSC-4, MDA-MB-468, MDA-MB-231, SCC-25 and THP-1. Periodontal ligament cells (PDLCs) were included as a noncancerous control. HMGN2 was detected in human oral squamous cell carcinoma tissues by immunohistochemical analysis...
April 2018: Oncology Letters
Chen Qu, Dandan Zheng, Sai Li, Yingjun Liu, Anna Lidofsky, Jacinta A Holmes, Jianning Chen, Lu He, Lan Wei, Yadi Liao, Hui Yuan, Qimeng Jin, Zelong Lin, Qiaoting Hu, Yuchuan Jiang, Mengxian Tu, Xijun Chen, Weiming Li, Wenyu Lin, Bryan C Fuchs, Raymond T Chung, Jian Hong
Spleen tyrosine kinase (SYK) plays a critical role in immune cell signaling pathways and has been reported as a novel biomarker for human hepatocellular carcinoma (HCC). We sought to investigate the mechanism by which SYK promotes liver fibrosis and to evaluate SYK as a therapeutic target for liver fibrosis. We evaluated the cellular localization of SYK and the association between SYK expression and liver fibrogenesis in normal, HBV-infected, HCV-infected and non-alcoholic steatohepatitis (NASH) liver tissue (n=36, 127, 22 and 30, respectively)...
March 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Di Ding, Lin-Lin Chen, Ying-Zhen Zhai, Chen-Jian Hou, Li-Li Tao, Shu-Han Lu, Jian Wu, Xiu-Ping Liu
Reversal of activated hepatic stellate cells (HSCs) to a quiescent state and apoptosis of activated HSCs are key elements in the reversion of hepatic fibrosis. CCAAT/enhancer binding protein α (C/EBP-α) has been shown to inhibit HSC activation and promote its apoptosis. This study aims to investigate how C/EBP-α acetylation affects the fate of activated HSCs. Effects of a histone deacetylation inhibitor trichostatin A (TSA) on HSC activation were evaluated in a mouse model of liver fibrosis caused by carbon tetrachloride (CCl4 ) intoxication...
March 13, 2018: Scientific Reports
Fang-Tian Bu, Yu Chen, Hai-Xia Yu, Xin Chen, Yang Yang, Xue-Yin Pan, Qin Wang, Yu-Ting Wu, Cheng Huang, Xiao-Ming Meng, Jun Li
SUMOylation and deSUMOylation, a dynamic process, is proved to be involved in various fibrotic diseases. Here, we found SENP2, one of deSUMOylation protease family member, was decreased in CCl4 -induced mice fibrotic liver tissues, primary HSCs and restored after spontaneously recovery. In addition, HSC-T6 cells with TGF-β1 treatment resulted in a significant reduction of SENP2. Ectopic expression of SENP2 hindered cells activation and proliferation induced by TGF-β1 while knockdown of SENP2 showed an opposite effect...
March 10, 2018: Toxicology Letters
Hiroyuki Motoyama, Akihiro Tamori, Shoji Kubo, Sawako Uchida-Kobayashi, Shigekazu Takemura, Shogo Tanaka, Satoko Ohfuji, Yuga Teranishi, Ritsuzo Kozuka, Etsushi Kawamura, Atsushi Hagihara, Hiroyasu Morikawa, Masaru Enomoto, Yoshiki Murakami, Norifumi Kawada
BACKGROUND: Hepatocellular carcinoma (HCC) develops in some patients who achieve sustained virological response (SVR) against hepatitis C virus (HCV) infection via anti-HCV therapy. To examine the pathogenesis of HCC development after HCV eradication, histopathological changes and clinical markers were evaluated in SVR patients. METHODS: Of 654 SVR patients treated with interferon (IFN)-based therapies, 34 patients who had undergone liver biopsy before initiating IFN therapy and after SVR achievement were enrolled: 11 patients with HCC and 23 patients without HCC (male/female, 9/2 and 8/15, respectively: age, 58 ± 5 and 54 ± 11 years, respectively)...
2018: PloS One
Liu-Lin Xiong, Yu Zou, Yu Shi, Piao Zhang, Rong-Ping Zhang, Xie-Jie Dai, Bin Liu, Ting-Hua Wang
The aim of the present study was to determine the effect of implanted neural stem cells (NSCs) on the functional recovery of tree shrews (TSs) subjected to hemi‑sectioned spinal cord injury (hSCI), and to investigate the possible mechanism involved. NSCs (passage 2), derived from the hippocampus of TSs (embryonic day 20), were labeled with Hoechst 33342 and transplanted intraspinally into the hSC of TSs at thoracic level 10 in the acute (immediately after injury) and chronic (day 9 post‑injury) stages...
March 9, 2018: International Journal of Molecular Medicine
Yuan-Liang Zhang, Jie-Wen Sun, Yin-Yin Xie, Yan Zhou, Ping Liu, Jia-Chun Song, Chun-Hui Xu, Lan Wang, Dan Liu, Ai-Ning Xu, Zhu Chen, Sai-Juan Chen, Xiao-Jian Sun, Qiu-Hua Huang
The histone H3 lysine 36 methyltransferase SETD2 is frequently mutated in various cancers, including leukemia. However, there has not been any functional model to show the contribution of SETD2 in hematopoiesis or the causal role of SETD2 mutation in tumorigenesis. In this study, using a conditional Setd2 knockout mouse model, we show that Setd2 deficiency skews hematopoietic differentiation and reduces the number of multipotent progenitors; although the number of phenotypic hematopoietic stem cells (HSCs) in Setd2-deleted mice is unchanged, functional assays, including serial BM transplantation, reveal that the self-renewal and competitiveness of HSCs are impaired...
March 12, 2018: Cell Research
Paula Gutierrez-Martinez, Leah Hogdal, Manavi Nagai, Miriama Kruta, Rumani Singh, Kristopher Sarosiek, Andre Nussenzweig, Isabel Beerman, Anthony Letai, Derrick J Rossi
Ageing of haematopoietic stem cells (HSCs) contributes to deficits in the aged haematopoietic system. HSC decline is driven in part by DNA damage accumulation; yet, how ageing impacts the acute DNA damage response (DDR) of HSCs is poorly understood. We show that old HSCs exhibit diminished ATM activity and attenuated DDR, leading to elevated clonal survival in response to a range of genotoxins that was underwritten by diminished apoptotic priming. Distinct HSC subsets exhibited ageing-dependent and subtype-dependent differences in apoptotic priming and survival in response to DNA damage...
March 12, 2018: Nature Cell Biology
Shaoyong Zhuang, Xiangwei Hua, Kang He, Tao Zhou, Jiang Zhang, Haoyu Wu, Xiong Ma, Qiang Xia, Jianjun Zhang
The contribution of glycogen synthase kinase-3β (GSK-3β) to cholestatic liver disease (CLD) remains unknown. We investigated the role and mechanism of GSK-3β in vivo in liver tissues of patients with CLD and the bile duct ligation (BDL) mouse model and in vitro using a hepatic progenitor cell (HPC) and hepatic stellate cell (HSC) coculture system. In liver tissues of patients with CLD, expression of the inactive form of GSK-3β, phospho-GSK-3β(Ser9), was increased in HPCs. GSK-3β inhibition by SB216763 treatment aggravated liver fibrosis and elevated the expression of osteopontin (OPN) in the BDL mouse model...
March 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Man K S Lee, Annas Al-Sharea, Dragana Dragoljevic, Andrew J Murphy
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) reside in the bone marrow and are important in replenishing all cells in the blood through a process termed hematopoiesis. One of the defining characteristics of HSCs is that they must be able to balance their self-renewal capacity with their differentiation into committed blood cells in various blood lineages. For these events to occur, HSCs must be tightly regulated in the bone marrow by intrinsic and extrinsic factors to maintain steady hematopoiesis...
March 9, 2018: Current Opinion in Lipidology
Jack P Carson, Grant A Ramm, Mark W Robinson, Donald P McManus, Geoffrey N Gobert
Hepatic fibrosis is a common pathology in various liver diseases. Hepatic stellate cells (HSCs) are the main cell type responsible for collagen deposition and fibrosis formation in the liver. Schistosomiasis is characterised by granulomatous fibrosis around parasite eggs trapped within the liver and other host tissues. This response is facilitated by the recruitment of immune cells and the activation of HSCs. The interactions between HSCs and schistosome eggs are complex and diverse, and a better understanding of these interactions could lead to improved resolution of fibrotic liver disease, including that associated with schistosomiasis...
March 8, 2018: Trends in Parasitology
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