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https://www.readbyqxmd.com/read/28637235/monotherapy-with-either-dolutegravir-or-raltegravir-fails-to-durably-suppress-hiv-viraemia-in-humanized-mice
#1
Alonso Heredia, Said Hassounah, Sandra Medina-Moreno, Juan C Zapata, Nhut M Le, Yingshan Han, James S Foulke, Charles Davis, Joseph Bryant, Robert R Redfield, Mark A Wainberg
Objectives: To compare the effectiveness of HIV integrase inhibitor monotherapy between raltegravir and dolutegravir as an approach to simplify therapy. Methods: We evaluated and compared the efficacy of 20 week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIV BaL . Plasma HIV RNA was measured by quantitative RT-PCR (limit of detection of 150 copies/45 μL of plasma) and drug levels by LC-MS/MS. Escape viruses were genotyped and analysed for replication capacity and drug susceptibility in tissue culture...
June 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28636890/memory-t-cells-a-helpful-guard-for-allogeneic-hematopoietic-stem-cell-transplantation-without-causing-graft-versus-host-disease
#2
REVIEW
Wei Huang, Nelson J Chao
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (AHSCT) and the major cause of nonrelapse morbidity and mortality of AHSCT. In AHSCT, donor T cells facilitate hematopoietic stem cell (HSC) engraftment, contribute to anti-infection immunity, and mediate graft-versus-leukemia (GVL) responses. However, activated alloreactive T cells also attack recipient cells in vital organs, leading to GVHD. Different T-cell subsets, including naïve T (TN) cells, memory T (TM) cells, and regulatory T (Treg) cells mediate different forms of GVHD and GVL; TN cells mediate severe GVHD, whereas TM cells do not cause GVHD, but preserve T-cell function including GVL...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28636545/reversal-effect-of-jagged1-signaling-inhibition-on-ccl4-induced-hepatic-fibrosis-in-rats
#3
Guiju Tang, Zhihong Weng, Jun Song, Yixiong Chen
The role of the Notch ligand Jagged1 in hepatic fibrosis remains to be elucidated. In the current study, we investigated the role of Jagged1 in the activation of hepatic stellate cells (HSCs) and development of hepatic fibrosis in rats. In vitro, Jagged1 in HSCs was downregulated and upregulated by Jagged1 siRNA and pcDNA3.1 Jagged1, respectively. The levels of epithelial-mesenchymal transition (EMT) markers and HSC activation markers were assessed using western blot analysis. The proliferation and migration capacity of HSCs were assessed using 5-ethynyl-2'-deoxyuridine (EdU) incorporation and Transwell migration assays...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635217/-the-exploration-on-optimization-of-two-alternatives-between-roll-test-and-dix-hallpike-test-in-benign-paroxysmal-positional-vertigo
#4
R Ji, T S Chen, W Wang, K X Xu, S S Li, C Wen, Q Liu, P Lin
Objective: To analyze the objective characteristics of roll test and Dix-Hallpike test in benign paroxysmal positional vertigo(BPPV)patients, discussing the premier solution of positional test. Methods: A total of 230 patients with BPPV, whereas 170 posterior semicircular canal canalithiasis (PSC-Can) BPPV and 60 horizontal semicircular canal canalithiasis (HSC-Can) BPPV were involved respectively. The induced nystagmus in roll test and Dix-Hallpike test was recorded by video nystagmuo graph (VNG), and the direction, intensity and time characteristics of nystagmus were compared in various BPPV...
June 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28634182/sf3b1-initiating-mutations-in-mds-with-ring-sideroblasts-target-lymphomyeloid-hematopoietic-stem-cells
#5
Teresa Mortera-Blanco, Marios Dimitriou, Petter S Woll, Mohsen Karimi, Edda Elvarsdottir, Simona Conte, Magnus Tobiasson, Monika Jansson, Iyadh Douagi, Matahi Moarii, Leonie Saft, Elli Papaemmanuil, Sten Eirik W Jacobsen, Eva Hellström-Lindberg
Mutations in the RNA splicing gene SF3B1 are found in more than 80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients, and were also present in downstream myeloid and erythroid progenitor cells...
June 20, 2017: Blood
https://www.readbyqxmd.com/read/28630423/thymosin-beta-4-regulates-activation-of-hepatic-stellate-cells-via-hedgehog-signaling
#6
Jieun Kim, Jeongeun Hyun, Sihyung Wang, Chanbin Lee, Jae-Wook Lee, Eun-Yi Moon, Heejae Cha, Anna Mae Diehl, Youngmi Jung
The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA-treated LX-2. TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630052/infection-exposure-promotes-etv6-runx1-precursor-b-cell-leukemia-via-impaired-h3k4-demethylases
#7
Guillermo Rodríguez-Hernández, Julia Hauer, Alberto Martín-Lorenzo, Daniel Schäfer, Christoph Bartenhagen, Idoia García-Ramírez, Franziska Auer, Ines Gonzalez-Herrero, Lucia Ruiz-Roca, Michael Gombert, Vera Okpanyi, Ute Fischer, Cai Chen, Martin Dugas, Sanil Bhatia, René M Linka, Marta Garcia-Suquia, María V Rascón-Trincado, Angel Garcia-Sanchez, Oscar Blanco, Maria Begona Garcia-Cenador, Francisco Javier Garcia-Criado, César Cobaleda, Diego Alonso-López, Javier De Las Rivas, Markus Müschen, Carolina Vicente-Dueñas, Isidro Sánchez-García, Arndt Borkhardt
<p>ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/peripheral cells (HSC/PC) and postnatal infections for human-like pB-ALL...
June 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28628927/curcumin-promotes-apoptosis-of-activated-hepatic-stellate-cells-by-inhibiting-protein-expression-of-the-myd88-pathway
#8
Ya-Jun He, Kenny Kuchta, Yan-Mei Deng, Silke Cameron, Yu Lin, Xu-You Liu, Guo-Ron Ye, Xia Lv, Yuta Kobayashi, Jian-Chang Shu
Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway...
June 19, 2017: Planta Medica
https://www.readbyqxmd.com/read/28627620/protective-effect-of-human-serum-amyloid-p-on-ccl4-induced-acute-liver-injury-in-mice
#9
Min Cong, Weihua Zhao, Tianhui Liu, Ping Wang, Xu Fan, Qingling Zhai, Xiaoli Bao, Dong Zhang, Hong You, Tatiana Kisseleva, David A Brenner, Jidong Jia, Hui Zhuang
Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression...
June 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28625745/lifelong-dietary-intervention-does-not-affect-hematopoietic-stem-cell-function
#10
Seka Lazare, Albertina Ausema, Aaffien C Reijne, Gertjan van Dijk, Ronald van Os, Gerald de Haan
Hematopoietic stem cells (HSC) undergo a profound functional decline during normal aging. As caloric or dietary restriction has been shown to delay multiple aspects of the aging process in many species, we here decided to explore the consequences of lifelong caloric restriction or, reversely, lifelong excess caloric intake for HSC numbers and function. Although caloric restriction prevented age-dependent increase in bone marrow cellularity, caloric restriction was not able to prevent functional decline of aged long-term hematopoietic stem cell functioning...
June 15, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28623783/scoparone-attenuates-hepatic-stellate-cell-activation-through-inhibiting-tgf-%C3%AE-smad-signaling-pathway
#11
Xing Liu, Xiuxia Zhao
Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. Scoparone, a major constituent isolated from Artemisia capillaris, was reported to possess hepatoprotective effect. However, the role of scoparone in liver fibrosis remains unknown. In the present study, we investigated the effects of scoparone on liver fibrosis in HSCs. Our results demonstrated that scoparoene inhibited the proliferation of HSCs exposed to transforming growth factor (TGF)-β1. In addition, scoparoene significantly suppressed TGF-β1-induced the expression of α-smooth muscle actin (α-SMA) and collagen I in HSC-T6 cells, as well as attenuated the expression of NADPH oxidase (NOX) isoforms expression and ROS production in TGF-β1-stimialted HSC-T6 cells...
June 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28623272/exosomes-derived-from-palmitic-acid-treated-hepatocytes-induce-fibrotic-activation-of-hepatic-stellate-cells
#12
Young-Sun Lee, So Yeon Kim, Eunjung Ko, Jun-Hee Lee, Hyon-Seung Yi, Yang Jae Yoo, Jihye Je, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Won-Il Jeong, Jong Eun Yeon, Soon Ho Um, Kwan Soo Byun
Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621467/critical-role-of-crebh-mediated-induction-of-tgf-%C3%AE-2-by-hcv-infection-in-fibrogenic-responses-in-hepatic-stellate-cells
#13
Takeshi Chida, Masahiko Ito, Kenji Nakashima, Yumi Kanegae, Takuya Aoshima, Shuji Takabayashi, Kazuhito Kawata, Yoshimi Nakagawa, Masahiro Yamamoto, Hitoshi Shimano, Tomokazu Matsuura, Yoshimasa Kobayashi, Takafumi Suda, Tetsuro Suzuki
Mechanisms of hepatic fibrogenesis induced by Hepatitis C virus (HCV), one of the leading causes of liver fibrosis, are not fully understood. We studied transcriptional up-regulation of transforming growth factor β (TGF-β), especially TGF-β2, which is mediated via the activation of liver-enriched transcription factor CREBH triggered by HCV infection and its functional significance for induction of profibrogenic phenotypes via interaction of HCV-infected cells with hepatic stellate cells (HSC). Compared to TGF-β1, expression of TGF-β2 mRNA was induced faster and to a higher level upon HCV infection...
June 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28618656/role-of-growth-factor-receptor-bound-2-in-ccl4-induced-hepatic-fibrosis
#14
Shanfei Ge, Ying Xiong, Xiaoping Wu, Jianping Xie, Fei Liu, Jinni He, Tianxing Xiang, Na Cheng, Lingling Lai, Yuanbin Zhong
BACKGROUND: Growth Factor Receptor-bound 2 (GRB2) plays a crucial role in regulation of cellular function including proliferation and differentiation, and we previously identified GRB2 as promoting HSCs (HSCs) proliferation. However, the underlying mechanisms that are involving in the regulation of GRB2 in hepatic fibrogenesis remain unknown. METHODS: In the present study, we tested the function of GRB2 in hepatic fibrosis. Hepatic fibrosis was induced by subcutaneous CCl4 administration at a dose of 3mL/kg in rats...
June 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28617435/interaction-between-autophagy-and-senescence-is-required-for-dihydroartemisinin-to-alleviate-liver-fibrosis
#15
Zili Zhang, Zhen Yao, Shifeng Zhao, Jiangjuan Shao, Anping Chen, Feng Zhang, Shizhong Zheng
Autophagy and cellular senescence are stress responses essential for homeostasis. Therefore, they may represent new pharmacologic targets for drug development to treat diseases. In this study, we sought to evaluate the effect of dihydroartemisinin (DHA) on senescence of activated hepatic stellate cells (HSCs), and to further elucidate the underlying mechanisms. We found that DHA treatment induced the accumulation of senescent activated HSCs in rat fibrotic liver, and promoted the expression of senescence markers p53, p16, p21 and Hmga1 in cell model...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28615446/lysosome-mediated-degradation-of-a-distinct-pool-of-lipid-droplets-during-hepatic-stellate-cell-activation
#16
Maidina Tuohetahuntila, Martijn R Molenaar, Bart Spee, Jos F Brouwers, Richard Wubbolts, Martin Houweling, Cong Yan, Hong Du, Brian C VanderVen, Arie B Vaandrager, J Bernd Helms
Activation of hepatic stellate cells (HSCs) is a critical step in the development of liver fibrosis. During activation, HSCs lose their lipid droplets (LDs) containing triacylglycerols (TAGs), cholesteryl esters (CEs) and retinyl esters (REs). We previously provided evidence for the presence of two distinct LD pools, a pre-existing and a dynamic LD pool. Here we investigate the mechanisms of neutral lipid metabolism in the pre-existing LD pool. To investigate the involvement of lysosomal degradation of neutral lipids, we studied the effect of lalistat, a specific lysosomal acid lipase (LAL/Lipa) inhibitor on LD degradation in HSCs during activation in vitro The LAL-inhibitor increased the levels of TAG, CE and RE in both rat and mouse HSCs...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615219/zfp521-regulates-murine-hematopoietic-stem-cell-function-and-facilitates-mll-af9-leukemogenesis-in-mouse-and-human-cells
#17
Brian S Garrison, Adrian P Rybak, Isabel Beerman, Balthasar Heesters, Francois E Mercier, David T Scadden, David Bryder, Roland Baron, Derrick J Rossi
The concept that tumor-initiating cells can co-opt the self-renewal program of endogenous stem cells as a means of enforcing their unlimited proliferative potential is widely accepted, yet identification of specific factors that regulate self-renewal of normal and cancer stem cells remains limited. Using a comparative transcriptomic approach, we identify ZNF521/Zfp521 as a conserved hematopoietic stem cell (HSC)-enriched transcription factor in human and murine hematopoiesis, whose function in HSC biology remains elusive...
June 14, 2017: Blood
https://www.readbyqxmd.com/read/28614719/systemic-virus-infections-differentially-modulate-cell-cycle-state-and-functionality-of-long-term-hematopoietic-stem-cells-in%C3%A2-vivo
#18
Christoph Hirche, Theresa Frenz, Simon F Haas, Marius Döring, Katharina Borst, Pia-K Tegtmeyer, Ilija Brizic, Stefan Jordan, Kirsten Keyser, Chintan Chhatbar, Eline Pronk, Shuiping Lin, Martin Messerle, Stipan Jonjic, Christine S Falk, Andreas Trumpp, Marieke A G Essers, Ulrich Kalinke
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28611447/serpinb3-promotes-pro-fibrogenic-responses-in-activated-hepatic-stellate-cells
#19
Erica Novo, Gianmarco Villano, Cristian Turato, Stefania Cannito, Claudia Paternostro, Chiara Busletta, Alessandra Biasiolo, Santina Quarta, Elisabetta Morello, Claudia Bocca, Antonella Miglietta, Ezio David, Salvatore Sutti, Mario Plebani, Emanuele Albano, Maurizio Parola, Patrizia Pontisso
SerpinB3 is a hypoxia- and hypoxia-inducible factor-2α-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth factor-β1, but the actual role of SerpinB3 in hepatic fibrogenesis is still poorly characterized. In the present study we analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611040/%C3%AE-catenin-is-a-candidate-therapeutic-target-for-myeloid-neoplasms-with-del-5q
#20
Liping Li, Yue Sheng, Wenshu Li, Chao Hu, Nupur Mittal, Kaoru Tohyama, Amber Seba, Youyang Zhao, Howard Ozer, Tongyu Zhu, Zhijian Qian
Deletion of the chromosome 5q [del(5q)] is one of the most common cytogenetic abnormalities observed in patients with de novo myelodysplastic syndromes (MDS) and therapy-related MDS or acute myeloid leukemia (t-MDS/tAML). Emerging evidence indicates that activation of the Wnt/β-catenin pathway contributes to the development of myeloid neoplasms with del(5q). Whether β-catenin is a potential therapeutic target for myeloid neoplasms with del(5q) has yet to be evaluated. Here we report that genetic deletion of a single allele of β-catenin rescues ineffective hematopoiesis in an Apc haploinsufficient mouse model, which recapitulates several characteristic features of the pre-leukemic stage of myeloid neoplasms with a -5/del(5q)...
June 13, 2017: Cancer Research
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