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Yiqing Pan, Yue Liu, Li Wang, Feng Xue, Yanqin Hu, Ran Hu, Chen Xu
Sertoli cells create a local tolerogenic microenvironment to maintain testicular immune privilege especially through the formation of a blood-testis barrier (BTB). However, the molecular mechanisms underlying the immune modulation function and BTB dynamics of Sertoli cells remained elusive. MAP phosphatase (MKP)-1 acts as a crucial negative regulator of the inflammatory response. Nevertheless, the role of MKP-1 in regulating Sertoli cells has not been elucidated. In this study, we have for the first time uncovered distinct cellular localization of MKP-1 in the cells at different stages of mouse testis, and the level of MKP-1 expression was significantly up-regulated by LPS-induced acute testis inflammation...
October 22, 2016: Oncotarget
Liang Xiao, Bo Yang, Xiaoyu Liu, Yan Luo, Qiongmei Ji, Zhong Wen, Zhigang Liu, Ping-Chang Yang
Food allergy (FA) is an adverse immune response to certain innocent food. It is estimated about 2% to 6% of the general population suffer from FA. Symptoms of a food allergic reaction may involve the gastrointestinal tract or/and other organs. The gut microbiota plays a critical role in diet-induced health problems. Whether the changes in the composition of the intestinal microbiota regulate allergic responses to food remains poorly understood. Thus, we created an FA animal model, sequenced the V4-V5 regions of 16S rRNA genes to characterize the genera abundance of gut microbiota...
October 21, 2016: Oncotarget
Lorena P Suarez-Kelly, Gregory M Kemper, Megan C Duggan, Andrew Stiff, Tiffany C Nole, Joseph Markowitz, Eric A Luedke, Vedat O Yildiz, Lianbo Yu, Alena Cristina Jaime-Ramirez, Volodymyr Karpa, Xiaoli Zhang, William E Carson
The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed...
October 21, 2016: Oncotarget
Cinthia C Stempin, Claudia C Motrán, María P Aoki, Cristian R Falcón, Fabio M Cerbán, Laura Cervi
Macrophage plasticity is critical for controlling inflammation including those produced by helminth infections, where alternatively activated macrophages (AAM) are accumulated in tissues. AAM expressing the co-inhibitory molecule programmed death ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasitic infections. However, the role of PD-L2 during F. hepatica infection has not yet been explored. We observed that F. hepatica infection or a F...
October 21, 2016: Oncotarget
Eloi R Verrier, Che C Colpitts, Charlotte Bach, Laura Heydmann, Laetitia Zona, Fei Xiao, Christine Thumann, Emilie Crouchet, Raphaël Gaudin, Camille Sureau, François-Loïc Cosset, Jane A McKeating, Patrick Pessaux, Yujin Hoshida, Catherine Schuster, Mirjam B Zeisel, Thomas F Baumert
Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3...
October 25, 2016: Cell Reports
Jeremy A Goettel, Roopali Gandhi, Jessica E Kenison, Ada Yeste, Gopal Murugaiyan, Sharmila Sambanthamoorthy, Alexandra E Griffith, Bonny Patel, Dror S Shouval, Howard L Weiner, Scott B Snapper, Francisco J Quintana
Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B...
October 25, 2016: Cell Reports
David S Wald, Jonathan P Bestwick, Joan K Morris, Ken Whyte, Lucy Jenkins, Nicholas J Wald
Background Child-parent screening for familial hypercholesterolemia has been proposed to identify persons at high risk for inherited premature cardiovascular disease. We assessed the efficacy and feasibility of such screening in primary care practice. Methods We obtained capillary blood samples to measure cholesterol levels and to test for familial hypercholesterolemia mutations in 10,095 children 1 to 2 years of age during routine immunization visits. Children were considered to have positive screening results for familial hypercholesterolemia if their cholesterol level was elevated and they had either a familial hypercholesterolemia mutation or a repeat elevated cholesterol level 3 months later...
October 27, 2016: New England Journal of Medicine
Patrick T Walsh, Padraic G Fallon
The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural antagonist IL-36Ra. The cytokines exert their effects through a specific IL-36 receptor consisting of IL-36R and IL-1RAcP chains. IL-36 cytokines can direct both innate and adaptive immune responses by acting on parenchymal, stromal, and specific immune cell subsets...
October 26, 2016: Annals of the New York Academy of Sciences
Nobuaki Suzuki, Shoichi Hazama, Haruo Iguchi, Kazuhiro Uesugi, Hiroaki Tanaka, Kosei Hirakawa, Atsushi Aruga, Takashi Hatori, Hidenobu Ishizaki, Yuzo Umeda, Toshiyoshi Fujiwara, Tetsuya Ikemoto, Mitsuo Shimada, Kazuhiko Yoshimatsu, Ryoichi Shimizu, Hiroto Hayashi, Koichiro Sakata, Hiroko Takenouchi, Hiroto Matsui, Yoshitaro Shindo, Michihisa Iida, Yasunobu Koki, Hideki Arima, Hiroyuki Furukawa, Tomio Ueno, Shigefumi Yoshino, Yusuke Nakamura, Masaaki Oka, Hiroaki Nagano
We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine...
October 26, 2016: Cancer Science
Laura Denise Mendes da Silva, Mariana Gatto, Mariana Miziara de Abreu Teodoro, Marjorie de Assis Golim, Érika Alessandra Pelisson Nunes da Costa, Francilene Capel Tavares Carvalho, Daniela Ramos Rodrigues, Paulo Câmara Marques Pereira, Ângela Maria Victoriano de Campos Soares, Sueli Aparecida Calvi
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi is a serious public health issue. Its evolution involves an acute stage, characterized by no specific symptoms, and the chronic stage during most individuals are asymptomatic, but about 30 to 40% of them become symptomatic presenting the cardiac or digestive disease. Host immune response mechanisms involved in symptomatic or asymptomatic chronic disease are not fully understood. The pro-inflammatory cytokines are crucial in host resistance. However, a fine control of this inflammatory process, by action of anti-inflammatory cytokines, is necessary to avoid tissue injury...
October 26, 2016: Scandinavian Journal of Immunology
T J Mai, R Ma, Z Li, S C Bi
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model...
October 24, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Sérgio Ferreira de Lima, Mayara Mansur Fernandes Tavares, Jamilly Lopes de Macedo, Renata Santos de Oliveira, Sandra de Andrade Heráclio, Maria de Mascena Diniz Maia, Paulo Roberto Eleutério de Souza, Ronald Moura, Sergio Crovella
Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil...
October 24, 2016: Memórias do Instituto Oswaldo Cruz
Layla Gomes Siravenha, Leonardo Quintão Siravenha, Lucimar Di Paula Madeira, Aldemir B Oliveira-Filho, Luiz Fernando Almeida Machado, Rosimar Neris Martins Feitosa, Antonio Carlos Rosário Vallinoto, Marluísa de Oliveira Guimarães Ishak, Ricardo Ishak
: The dental pulp is a sterile highly vascularized tissue and has been commonly used as a biological material to detect the genome of infectious agents that reach the dental tissue. Indeed, the pulp is also used to reveal past and ancient infections in the field of paleomicrobiology. The present study aimed to detect the presence of Hepatitis C virus (HCV) in a small community (approximately 400 inhabitants) in the Amazon region of Brazil (Nossa Senhora do Perpetuo Socorro, Vizeu, Para, Brazil) and standardize a technique for the detection of the virus in the dental pulp...
2016: PloS One
Kshipra Singh, Nicole T Al-Greene, Thomas G Verriere, Lori A Coburn, Mohammad Asim, Daniel P Barry, Margaret M Allaman, Dana M Hardbower, Alberto G Delgado, M Blanca Piazuelo, Bruce A Vallance, Alain P Gobert, Keith T Wilson
Solute carrier family 7 member 2 (SLC7A2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in immune responses to pathogens. We assessed the role of SLC7A2 in murine infection with Citrobacter rodentium, an attaching and effacing enteric pathogen that causes colitis. Induction of SLC7A2 was upregulated in colitis tissues, and localized predominantly to colonic epithelial cells. Compared to wild-type mice, Slc7a2-/-mice infected with C. rodentium had improved survival and decreased weight loss, colon weight, and histologic injury; this was associated with decreased colonic macrophages, dendritic cells, granulocytes, and Th1 and Th17 cells...
October 2016: PLoS Pathogens
Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Pavan Kumar Nathella, Padmaja Paidipally, Munenori Ishibashi, Elwyn Welch, Amy R Tvinnereim, Mitsuo Ikebe, Vijaya Lakshmi Valluri, Subash Babu, Hardy Kornfeld, Ramakrishna Vankayalapati
In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice...
October 2016: PLoS Pathogens
Chwan Hong Foo, Christina L Rootes, Karla Cowley, Glenn A Marsh, Cathryn M Gould, Celine Deffrasnes, Christopher J Cowled, Reuben Klein, Sarah J Riddell, Deborah Middleton, Kaylene J Simpson, Lin-Fa Wang, Andrew G D Bean, Cameron R Stewart
Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded microRNAs (miRNAs) impacting henipavirus infection in human cells. Members of the miR-181 and miR-17~93 families strongly promoted Hendra virus infection...
October 2016: PLoS Pathogens
Ines Rama, Ines Llaudó, Pere Fontova, Gema Cerezo, Carlos Soto, Casimiro Javierre, Miguel Hueso, Nuria Montero, Alberto Martínez-Castelao, Juan Torras, Josep M Grinyó, Josep M Cruzado, Nuria Lloberas
BACKGROUND: Patients undergoing conventional hemodialysis (C-HD) present a greater immuno-inflammatory state probably related to uremia, sympathetic nervous system (SNS) activation and /or membrane bioincompatibility, which could improve with a technique-switching to online hemodiafiltration (OL-HD). The antigen-independent pathway activation of this modified immunologic state turns dendritic cells (DC) into an accurate cell model to study these patients. The aim of this study is to further evaluate the immune-inflammatory state of patients in C-HD assessed by DC maturation...
2016: PloS One
Elisa Terracciano, Ermanno Zorzoli, Gian Loreto D'Alò, Laura Zaratti, Elisabetta Franco
Vaccinations and the controversy around them always go in parallel. We identified four categories blending in various amounts of truth and imagination: history, myths, shams and frauds. Over the years, they have alternated and sometimes transformed into one another. This sharp separation into categories is certainly academic and forced. In fact, the line between these aspects is not clear enough to allow a rigid and well-defined division. Our work starts from the category containing the most truthfulness: history, and goes on to analyze two categories that add fantasy to facts: myths and shams (or better, "old wives' tales")...
July 2016: Igiene e Sanità Pubblica
Xiurong Yu, Hongying Sun, Xiangyun Lin, Xiuxiang Liu
BACKGROUND Breast feeding can enhance preterm infants' neurodevelopmental outcome, regulate immune function development. This study aims to develop breastfeeding evaluation indicators system in neonatal intensive care units (NICU) and to provide theoretical basis for all-round evaluation of breast feeding quality for hospitalized preterm infants. MATERIAL AND METHODS This study was performed based on Avedis Donabedian's theory of medical care quality. Preterm infant breast feeding evaluation indicators system frame was initially formed by using literature review, clinical on-spot observation and expert consultation methods...
October 26, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Luis Sendra Gisbert, Antonio Miguel Matas, Luis Sabater Ortí, María José Herrero Cervera, Laura Sabater Olivas, Eva María Montalvá Orón, Matteo Frasson, Rafael Abargues López, Rafael López-Andújar, Eduardo García-Granero Ximénez, Salvador Francisco Aliño Pellicer
: Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. Immunosuppressant drugs permitted improving organ transplantation but they cannot completely solve the problem and their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required...
October 26, 2016: Liver Transplantation
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