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Yasmine Baktash, Anisha Madhav, Kelly E Coller, Glenn Randall
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms...
March 14, 2018: Cell Host & Microbe
Vandana Sekhar, Teresa Pollicino, Giacomo Diaz, Ronald E Engle, Farah Alayli, Marta Melis, Juraj Kabat, Ashley Tice, Anna Pomerenke, Nihal Altan-Bonnet, Fausto Zamboni, Paolo Lusso, Suzanne U Emerson, Patrizia Farci
Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication...
March 14, 2018: PLoS Pathogens
Zakia Abu-Zahab, Niveen M Gad, Seham Sabry, Sherif A Nassib
Systemic Lupus Erythematosus is systematic auto-immune disease characterized by abnormal activation of B cell with production of autoantibodies. Due to its heterogeneous course, there is a need for new markers to help in diagnosing and monitoring disease activity. The aim of this study was to identify the immunopathological role of CD19 and CD81 expression in patients with SLE and their correlation with the disease activity. Peripheral blood (PB) was collected from 40 SLE patients (20 active and 20 inactive) and 20 controls...
June 2017: Egyptian Journal of Immunology
Ting Shen, Qing-Qing Zheng, Jiang Shen, Qiu-Shi Li, Xing-Hui Song, Hong-Bo Luo, Chao-Yang Hong, Ke Yao
Background: Corneal stromal cells (CSCs) are components of the corneal endothelial microenvironment that can be induced to form a functional tissue-engineered corneal endothelium. Adipose-derived mesenchymal stem cells (ADSCs) have been reported as an important component of regenerative medicine and cell therapy for corneal stromal damage. We have demonstrated that the treatment with ADSCs leads to phenotypic changes in CSCs in vitro. However, the underlying mechanisms of such ADSC-induced changes in CSCs remain unclear...
March 20, 2018: Chinese Medical Journal
Lucio Barile, Elisabetta Cervio, Vincenzo Lionetti, Giuseppina Milano, Alessandra Ciullo, Vanessa Biemmi, Sara Bolis, Claudia Altomare, Marco Matteucci, Dario Disilvestre, Tudor Emanuel Fertig, Tiziano Torre, Stefanos Demertzis, Pierluigi Mauri, Tiziano Moccetti, Giuseppe Vassalli
Aims: Cell therapy trials using cardiac-resident progenitor cells (CPCs) and bone marrow-derived mesenchymal stem/progenitor cells (BMCs) in patients after myocardial infarction have provided encouraging results. Exosomes, nanosized extracellular vesicles of endosomal origin, figure prominently in the bioactivities of these cells. However, a head-to-head comparison of exosomes from the two cell types has not been performed yet. Methods and Results: CPCs and BMCs were derived from cardiac atrial appendage specimens and sternal bone marrow, respectively, from patients (n=20; age, 69...
March 5, 2018: Cardiovascular Research
E Tsitsikov, M H Harris, L B Silverman, S E Sallan, O K Weinberg
INTRODUCTION: Minimal residual disease (MRD) in B lymphoblastic leukemia has been demonstrated to be a powerful predictor of clinical outcome in numerous studies in both children and adults. In this study, we evaluated 86 pediatric patients with both diagnostic and remission flow cytometry studies and compared expression of CD81, CD58, CD19, CD34, CD20, and CD38 in the detection of MRD. METHODS: We evaluated 86 patients with B lymphoblastic leukemia who had both diagnostic studies and remission studies for the presence of MRD using multicolor flow cytometry...
March 2, 2018: International Journal of Laboratory Hematology
Laura Riva, Ok-Ryul Song, Jannick Prentoe, François Helle, Laurent L'homme, Charles-Henry Gattolliat, Alexandre Vandeputte, Lucie Fénéant, Sandrine Belouzard, Thomas F Baumert, Tarik Asselah, Jens Bukh, Priscille Brodin, Laurence Cocquerel, Yves Rouillé, Jean Dubuisson
Hepatitis C virus (HCV) infection causes 500,000 deaths annually, associated with end-stage liver diseases. Investigations of the HCV life cycle widened the knowledge in virology, and here we discovered that two piperazinylbenzenesulfonamides inhibit HCV entry into liver cells. The entry process of HCV into host cells is a complex process, not fully understood, but characterized by multiple spatially and temporally regulated steps involving several known host factors. Through a high-content virus-infection screening analysis with a library of 1,120 biologically active chemical compounds, we identified SB258585, an antagonist of the serotonin receptor 6 (5-HT6), as a new inhibitor of HCV entry in liver-derived cell lines, as well as in primary hepatocytes...
February 28, 2018: Journal of Virology
Yongshun Ma, Bo Pan, Haoxuan Yang, Izhar Hyder Qazi, Zhenzheng Wu, Changjun Zeng, Ming Zhang, Qingyong Meng, Guangbin Zhou
The present study aimed to investigate the effect of vitrification on the expression of fertilization related genes (CD9 and CD81) and DNA methyl transferases (DNMT1 and DNMT3b) in bovine germinal vesicle (GV) oocytes and their resulting metaphase Ⅱ (MⅡ) stages after in vitro maturation culture. GV oocytes were vitrified using the open-pulled straw method; after warming, they were cultured in vitro. The vitrified-warmed GV oocytes and more developed MII oocytes were used to calculate the maturation rates (first polar body extrusion under a stereomicroscopy), and to detect mRNA expression (qRT-PCR)...
February 21, 2018: Cryobiology
Hui Fang, Shuai Shao, Man Jiang, Erle Dang, Shengxian Shen, Jieyu Zhang, Pei Qiao, Caixia Li, Gang Wang
Bullous pemphigoid is an autoimmune inflammatory disorder characterised by the presence of autoantibodies against bullous pemphigoid autoantigens, leading to dermal-epidermal separation with consequent blister formation. However, whether and how the components of blister fluid exacerbate the progression of bullous pemphigoid is unclear. Exosomes are nanometre-sized vesicles released from cells into the body fluid, where they can transmit signals throughout the body. In the present study, we isolated and characterised exosomes from the blister fluids of patients with bullous pemphigoid, evaluated their proinflammatory role, and identified the underlying molecular mechanisms...
February 22, 2018: Journal of Pathology
Jun Gu, Joshua Hardy, Irene Boo, Patricia Vietheer, Kathleen McCaffrey, Yousef Alhammad, Abha Chopra, Silvana Gaudieri, Pantelis Poumbourios, Fasséli Coulibaly, Heidi E Drummer
The Hepatitis C Virus (HCV) E2 glycoprotein is a major target of the neutralizing antibody response with multiple type-specific and broadly neutralizing antibody epitopes identified. The 412-423 region can generate broadly neutralizing antibodies (bnNAbs) that block interaction with the cell surface receptor CD81, with activity towards multiple HCV genotypes. In this study we reveal the structure of the rodent MAb24 with an extensive contact area towards a peptide spanning the 412-423 region. The crystal structure of the MAb24-peptide 412-423 complex reveals the paratope bound to a peptide hairpin, highly similar to that observed with human MAb HCV1, but with a different angle of approach...
February 21, 2018: Journal of Virology
Sergey E Sedykh, Lada V Purvinish, Artem S Monogarov, Evgeniya E Burkova, Alina E Grigor'eva, Dmitrii V Bulgakov, Pavel S Dmitrenok, Valentin V Vlassov, Elena I Ryabchikova, Georgy A Nevinsky
Exosomes are 40-100 nm nanovesicles containing RNA and different proteins. Exosomes containing proteins, lipids, mRNAs, and microRNAs are important in intracellular communication and immune function. Exosomes from different sources are usually obtained by combination of centrifugation and ultracentrifugation and according to published data can contain from a few dozens to thousands of different proteins. Crude exosome preparations from milk of eighteen horses were obtained for the first time using several standard centrifugations...
June 2017: Biochimie Open
Young-Chan Kwon, Keith Meyer, Guangyong Peng, Soumya Chatterjee, Daniel F Hoft, Ranjit Ray
A comprehensive strategy to control HCV infection needs a vaccine. Our phase I study with recombinant HCV E1/E2 EnvGPs as a candidate vaccine did not induce a strong immune response in volunteers. We analyzed the interactions of HCV EnvGPs with human monocyte derived macrophages as antigen presenting cells. HCV E2 induced immune regulatory cytokine IL-10 and sCD163 protein expression in macrophages from 7 of 9 blood donors tested. Further, HCV E2 enhanced Stat3 and suppressed Stat1 activation, reflecting macrophage polarization towards M2 phenotype...
February 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Edward J Goetzl, Janice B Schwartz, Erin L Abner, Gregory A Jicha, Dimitrios Kapogiannis
OBJECTIVE: Astrocytes fulfill neuronal trophic roles normally, but are transformed in Alzheimer's disease (AD) into A1-type reactive astrocytes that may destroy neurons through unknown mechanisms. METHODS: To investigate astrocyte inflammatory mechanisms, astrocyte-derived exosomes (ADEs) were isolated immunochemically from plasmas of AD patients and matched controls for ELISA quantification of complement proteins. RESULTS: ADE levels of C1q, C4b, C3d, factor B, factor D, Bb, C3b and C5b-C9 terminal complement complex (TCC), but not mannose-binding lectin (MBL), normalized by the CD81 exosome marker were significantly higher for AD patients (n=28) than age- and gender-matched controls (all p<0...
February 6, 2018: Annals of Neurology
Qi Gao, Venkata Yellapantula, Maly Fenelus, Janine Pichardo, Lu Wang, Ola Landgren, Ahmet Dogan, Mikhail Roshal
CD99(MIC2) is a widely expressed cell surface glycoprotein and functions as a tumor suppressor involved in downregulation of SRC family of tyrosine kinase. CD99 expression is tightly regulated through B-cell development. The principal aims of this study were to investigate the clinical utility of CD99 expression (i) in distinguishing normal plasma cells from primary plasma cell neoplasms; (ii) in detection of minimal residual disease in primary plasma cell neoplasms; and (iii) in distinguishing plasma cell component of B-cell lymphomas from primary plasma cell neoplasms...
February 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Tadashi Maemura, Satoshi Fukuyama, Yukihiko Sugita, Tiago J S Lopes, Tomomi Nakao, Takeshi Noda, Yoshihiro Kawaoka
Exosomes regulate cell-cell communication by transferring functional proteins and RNAs between cells. Here, to clarify the function of exosomes during influenza virus infection, we characterized lung-derived exosomal microRNAs (miRNAs). Among the detected miRNAs, miR-483-3p was present at high levels in bronchoalveolar lavage fluid (BALF) exosomes during infection of mice with various strains of influenza virus, and miR-483-3p transfection potentiated gene expression of type I interferon and proinflammatory cytokine upon viral infection of MLE-12 cells...
January 24, 2018: Journal of Infectious Diseases
Yongyut Pewkliang, Siriwan Rungin, Kaewta Lerdpanyangam, Apisak Duangmanee, Phongthon Kanjanasirirat, Phichaya Suthivanich, Khanit Sa-Ngiamsuntorn, Suparerk Borwornpinyo, Jetsumon Sattabongkot, Rapatbhorn Patrapuvich, Suradej Hongeng
BACKGROUND: Eradication of malaria is difficult because of the ability of hypnozoite, the dormant liver-stage form of Plasmodium vivax, to cause relapse in patients. Research efforts to better understand the biology of P. vivax hypnozoite and design relapse prevention strategies have been hampered by the lack of a robust and reliable model for in vitro culture of liver-stage parasites. Although the HC-04 hepatoma cell line is used for culturing liver-stage forms of Plasmodium, these cells proliferate unrestrictedly and detach from the culture dish after several days, which limits their usefulness in a long-term hypnozoite assay...
January 25, 2018: Malaria Journal
Eliana Amati, Omar Perbellini, Gianluca Rotta, Martina Bernardi, Katia Chieregato, Sabrina Sella, Francesco Rodeghiero, Marco Ruggeri, Giuseppe Astori
BACKGROUND: Mesenchymal stromal cells (MSC) are a heterogeneous population of multipotent progenitors used in the clinic because of their immunomodulatory properties and their ability to differentiate into multiple mesodermal lineages. Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can be collected noninvasively and without major ethical concerns. Comparative studies comprehensively characterizing the MSC phenotype across several tissue sources are still lacking...
January 16, 2018: Stem Cell Research & Therapy
Qingyi Zhang, Lin Fu, Yahui Liang, Zikuan Guo, Lisheng Wang, Cong Ma, Hengxiang Wang
Mesenchymal stem cells (MSCs) have been approved as a cellular drug for the treatment of a variety of immune-related diseases by the government of many countries'. Previous investigations, including ours, have shown that exosomes secreted by MSCs (MSC-ex) are one of the main factors responsible for the therapeutic effect of MSCs. However, the immune modulation activities and the contents of MSC-ex derived from cells under different incubation conditions differ dramatically. Therefore, the optimal way to ensure effectiveness is by identifying and preparing MSC-ex with confirmed potent immunosuppressive activity...
January 16, 2018: Journal of Cellular Physiology
Alla Kachko, Maria Isabel Costafreda, Iryna Zubkova, Jerome Jacques, Kazuyo Takeda, Frances Wells, Gerardo Kaplan, Marian E Major
Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. Several host molecules participate in HCV cell entry but this process remains unclear. The complete unraveling of the HCV entry process is important to further understand viral pathogenesis and develop therapeutics. The human hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, functions as a phospholipid receptor involved in cell entry of several enveloped viruses. Here, we studied the role of HAVCR1 in HCV infection...
January 10, 2018: Journal of Virology
Ye Tian, Ling Ma, Manfei Gong, Guoqiang Su, Shaobin Zhu, Wenqiang Zhang, Shuo Wang, Zhibin Li, Chaoxiang Chen, Lihong Li, Lina Wu, Xiaomei Yan
Extracellular vesicles (EVs) have stimulated considerable scientific and clinical interest, yet protein profiling and sizing of individual EVs remains challenging due to their small particle size, low abundance of proteins, and overall heterogeneity. Building upon a laboratory-built high-sensitivity flow cytometer (HSFCM), we report here a rapid approach for quantitative multiparameter analysis of single EVs down to 40 nm with an analysis rate up to 10,000 particles per minute. Statistically robust particle size distribution was acquired in minutes with a resolution and profile well matched with those of cryo-TEM measurements...
January 4, 2018: ACS Nano
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