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https://www.readbyqxmd.com/read/29160853/therapeutic-strategies-against-epstein-barr-virus-associated-cancers-using-proteasome-inhibitors
#1
REVIEW
Kwai Fung Hui, Kam Pui Tam, Alan Kwok Shing Chiang
Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral lytic reactivation, modify cell cycle checkpoints, prevent apoptosis and evade immune surveillance. In this review, we aim to provide an overview of the mechanisms by which the virus manipulates the ubiquitin-proteasome system in EBV-associated lymphoid and epithelial malignancies, to evaluate the efficacy of proteasome inhibitors on the treatment of these cancers and discuss potential novel viral-targeted treatment strategies against the EBV-associated cancers...
November 21, 2017: Viruses
https://www.readbyqxmd.com/read/29155454/harnessing-the-power-of-regulatory-t-cells-to-control-autoimmune-diabetes-overview-and-perspective
#2
REVIEW
Hua Yu, Ricardo Paiva, Richard A Flavell
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T cells (Teff) and regulatory T cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity...
November 20, 2017: Immunology
https://www.readbyqxmd.com/read/29155208/inflammatory-renin-angiotensin-system-disruption-attenuates-sensory-hyperinnervation-and-mechanical-hypersensitivity-in-a-rat-model-of-provoked-vestibulodynia
#3
Anuradha Chakrabarty, Zhaohui Liao, Ying Mu, Peter G Smith
Vestibulodynia is characterized by peri-vaginal mechanical hypersensitivity, hyperinnervation, and abundant inflammatory cells expressing renin-angiotensin system proteins. We developed a tractable rat model of vestibulodynia to further assess the contributions of the renin-angiotensin system. Complete Freund's adjuvant (CFA) injected into the posterior vestibule induced marked vestibular hypersensitivity throughout a 7-day test period. Numbers of axons immunoreactive for PGP9.5, calcitonin gene-related peptide, and GFRα2 were increased...
November 15, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29154208/characteristics-of-nk-cells-from-leukemic-microenvironment-in-mll-af9-induced-acute-myeloid-leukemia
#4
Feifei Yang, Rong Wang, Wenli Feng, Chong Chen, Xiao Yang, Lina Wang, Yuting Hu, Qian Ren, Guoguang Zheng
NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment. However, their characteristics in leukemic microenvironment, including maturation status, phenotype, subpopulations and functional roles especially immunoregulatory potential, have not been well established. Here, we studied these characteristics of NK cells in MLL-AF9 induced mouse acute myeloid leukemia (AML) model...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29152448/vision-assisted-micromanipulation-using-closed-loop-actuation-of-multiple-microrobots
#5
M Arifur Rahman, Noboru Takahashi, Kawai F Siliga, Nigel K Ng, Zhidong Wang, Aaron T Ohta
Accurate control and precise positioning of opto-thermocapillary flow-addressed bubble microrobots are necessary for micromanipulation. In addition, micromanipulation using the simultaneous actuation of multiple microrobots requires a robust control system to enable independent motion. This paper demonstrates a hybrid closed-loop vision-assisted control system capable of actuating multiple microrobots simultaneously and positioning them at precise locations relative to micro-objects under manipulation. A vision-assisted grasp-planning application was developed and used to calculate the necessary trajectories of the microrobots to form cages around micro-objects...
2017: Robotics and Biomimetics
https://www.readbyqxmd.com/read/29152027/design-considerations-for-open-well-microfluidic-platforms-for-hypoxic-cell-studies
#6
Matthew B Byrne, Matthew T Leslie, Heeral S Patel, H Rex Gaskins, Paul J A Kenis
Regions of hypoxia are common in solid tumors and are associated with enhanced malignancy, metastasis, and chemo/radio resistance. Real-time hypoxic cellular experimentation is challenging due to the constant need for oxygen control. Most microfluidic platforms developed thus far for hypoxic cell studies are burdened by complex design parameters and are difficult to use for uninitiated investigators. However, open-well microfluidic platforms enable short and long term hypoxic cell studies with an ease of use workflow...
September 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/29150659/ectopic-foxp3-expression-preserves-primitive-features-of-human-hematopoietic-stem-cells-while-impairing-functional-t-cell-differentiation
#7
F R Santoni de Sio, L Passerini, M M Valente, F Russo, L Naldini, M G Roncarolo, R Bacchetta
FOXP3 is the transcription factor ruling regulatory T cell function and maintenance of peripheral immune tolerance, and mutations in its coding gene causes IPEX autoimmune syndrome. FOXP3 is also a cell-cycle inhibitor and onco-suppressor in different cell types. In this work, we investigate the effect of ectopic FOXP3 expression on HSC differentiation and we challenged this approach as a possible HSC-based gene therapy for IPEX. FOXP3-expressing HSC showed reduced proliferation ability and increased maintenance of primitive markers in vitro in both liquid and OP9-ΔL1 co-cultures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29147615/tumor-associated-neutrophils-induce-apoptosis-of-non-activated-cd8-t-cells-in-a-tnf%C3%AE-and-no-dependent-mechanism-promoting-a-tumor-supportive-environment
#8
Janna Michaeli, Merav E Shaul, Inbal Mishalian, Avi-Hai Hovav, Liran Levy, Lidia Zolotriov, Zvi Granot, Zvi G Fridlender
The role of neutrophils in tumor progression has become in recent years a subject of growing interest. Tumor-associated neutrophils (TANs), which constitute an important portion of the tumor microenvironment, promote immunosuppression in advanced tumors by modulating the proliferation, activation and recruitment of a variety of immune cell types. Studies which investigated the consequences of manipulating TAN polarization suggest that the impact of these neutrophils on tumor progression is considerably mediated by and dependent on the presence of CD8 T-cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29144203/suppression-or-activation-of-immune-responses-by-predicted-secreted-proteins-of-the-soybean-rust-pathogen-phakopsora-pachyrhizi
#9
Mingsheng Qi, James P Grayczyk, Janina M Seitz, Youngsill Lee, Tobias I Link, Doil Choi, Kerry F Pedley, Ralf T Voegele, Thomas J Baum, Steven A Whitham
Rust fungi, such as the soybean rust pathogen Phakopsora pachyrhizi, are major threats to crop production. They form specialized haustoria that are hyphal structures intimately associated with host-plant cell membranes. These haustoria have roles in acquiring nutrients and secreting effector proteins that manipulate host immune systems. Functional characterization of effector proteins of rust fungi is important for understanding mechanisms that underlie their virulence and pathogenicity. Hundreds of candidate effector proteins have been predicted for rust pathogens, but it is not clear how to prioritize these effector candidates for further characterization...
November 16, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29143962/comparison-of-gene-expression-in-post-smolt-atlantic-salmon-challenged-by-lf-89-like-and-em-90-like-piscirickettsia-salmonis-isolates-reveals-differences-in-the-immune-response-associated-with-pathogenicity
#10
M Rozas-Serri, A Peña, G Arriagada, R Enríquez, L Maldonado
Piscirickettsiosis is the main bacterial disease affecting the Chilean salmon farming industry and is responsible for high economic losses. The aim of this study was to describe and comparatively quantify the immune response of post-smolt Atlantic salmon infected by cohabitation with fish bearing LF-89-like and EM-90-like Piscirickettsia salmonis. The expression of 17 genes related to the immune response was studied in head kidney from cohabitant fish by RT-qPCR. Our results at the transcriptomic level suggest that P...
November 16, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29140108/cytomegalovirus-and-hiv-persistence-pouring-gas-on-the-fire
#11
Aaron Christensen-Quick, Christophe Vanpouille, Andrea Lisco, Sara Gianella
The inherent stability of a small population of T cells that are latently infected with HIV despite antiretroviral therapy (ART) remains a stubborn obstacle to an HIV cure. By exploiting the memory compartment of our immune system, HIV maintains persistence in a small subset of quiescent cells with varying phenotypes, thus evading immune surveillance and clinical detection. Understanding the molecular and immunological mechanisms that maintain the latent reservoir will be critical to the success of HIV eradication strategies...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29126914/targeting-immuno-metabolism-to-improve-anti-cancer-therapies
#12
Kevin Beezhold, Craig A Byersdorfer
The immunology community has made significant strides in recent years in using the immune system to target and eliminate cancer. Therapies such as hematopoietic stem cell transplantation (HSCT) are the standard of care treatment for several malignancies, while therapies incorporating chimeric antigen receptor (CAR) T cells or checkpoint molecule blockade have been revolutionary. However, these approaches are not optimal for all cancers and in some cases, have failed outright. The greatest obstacle to making these therapies more effective may be rooted in one of the most basic concepts of cell biology, metabolism...
November 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29126597/role-of-autophagy-in-mhc-class-i-restricted-antigen-presentation
#13
Luc Van Kaer, Vrajesh V Parekh, J Luke Postoak, Lan Wu
Major histocompatibility complex (MHC) class I molecules present peptide antigens to MHC class I-restricted CD8(+) T lymphocytes. The peptides loaded onto MHC class I molecules are typically derived from cytosolic antigens, which includes both self and foreign proteins. In addition to this classical MHC class I antigen presentation pathway, some cell types, especially dendritic cells can present antigens from exogenous sources to MHC class I-restricted CD8(+) T cells, in a process called cross-presentation...
November 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29118008/ctla-4-a-moving-target-in-immunotherapy
#14
Behzad Rowshanravan, Neil Halliday, David M Sansom
CD28 and CTLA-4 are members of a family of Immunoglobulin-related receptors that are responsible for various aspects of T cell immune regulation. The family includes CD28, CTLA-4 and ICOS as well as other proteins including PD-1, BTLA and TIGIT. These receptors have both stimulatory (CD28, ICOS) as well as inhibitory roles (CTLA-4, PD-1, BTLA and TIGIT) in T cell function. Increasingly these pathways are targeted as part of immune modulatory strategies to treat cancers, referred to generically as immune checkpoint blockade, and conversely to treat autoimmunity and CTLA-4 deficiency...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29113524/how-does-preeclampsia-affect-neonates-highlights-in-the-disease-s-immunity
#15
Lina R Marins, Leonardo B Anizelli, Ana L Sarquis, Mariana D Romanowski
INTRODUCTION: Preeclampsia (PE) is the primary obstetrical cause in one to four perinatal deaths. Although the etiology and pathogenesis of preeclampsia is not fully known, a proinflammatory immune state prevails and can disrupt fetal hematopoiesis. Some of the effects on the newborn include neonatal thrombocytopenia, neutropenia, a reduction in T regulatory cells and an increased cytotoxic natural killer cell profile. METHOD: Electronic databases were searched, and defined criteria were applied to select articles for review...
November 7, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29106928/epithelial-mesenchymal-stem-cell-transition-in-a-human-organ-lessons-from-lichen-planopilaris
#16
H Imanishi, D M Ansell, J Chéret, M Harries, M Bertolini, N Sepp, T Bíró, E Poblet, F Jimenez, J Hardman, S Parameswara Panicker, C M Ward, R Paus
Epithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles (HFs), during the inflammatory permanent alopecia, lichen planopilaris (LPP). We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with TGF-ß1, EGF, and interferon-γ administration, which to our knowledge is previously unreported...
October 26, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29104504/host-cell-vimentin-restrains-toxoplasma-gondii-invasion-and-phosphorylation-of-vimentin-is-partially-regulated-by-interaction-with-tgrop18
#17
Cheng He, Ling Kong, Lijuan Zhou, Jing Xia, Haixia Wei, Min Liu, Hongjuan Peng
The obligate intracellular parasite, Toxoplasma gondii, manipulates the cytoskeleton of its host cells to facilitate infection. A significant rearrangement of host cell vimentin around Toxoplasma parasitophorous vacuoles is observed during the course of infection. ROP18 (TgROP18) is a serine-threonine kinase secreted by T. gondii rhoptry and a major virulence factor; however, the mechanisms by which this kinase modulates host factors remain poorly understood. Different and dynamic patterns of vimentin solubility, phosphorylation, and expression levels were observed in host cells infected with T...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29100506/long-term-in-vitro-culture-of-plasmodium-vivax-isolates-from-madagascar-maintained-in-saimiri-boliviensis-blood
#18
Rajeev K Mehlotra, D'Arbra Blankenship, Rosalind E Howes, Tovonahary A Rakotomanga, Brune Ramiranirina, Stephanie Ramboarina, Thierry Franchard, Marlin H Linger, Melinda Zikursh-Blood, Arsène C Ratsimbasoa, Peter A Zimmerman, Brian T Grimberg
BACKGROUND: Plasmodium vivax is the most prevalent human malaria parasite and is likely to increase proportionally as malaria control efforts more rapidly impact the prevalence of Plasmodium falciparum. Despite the prominence of P. vivax as a major human pathogen, vivax malaria qualifies as a neglected and under-studied tropical disease. Significant challenges bringing P. vivax into the laboratory, particularly the capacity for long-term propagation of well-characterized strains, have limited the study of this parasite's red blood cell (RBC) invasion mechanism, blood-stage development, gene expression, and genetic manipulation...
November 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29099039/cytokine-signaling-in-multiple-sclerosis-and-its-therapeutic-applications
#19
REVIEW
Pushpalatha Palle, Kelly L Monaghan, Sarah M Milne, Edwin C K Wan
Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known but it is widely accepted that it is autoimmune in nature. Disease onset is believed to be initiated by the activation of CD4+ T cells that target autoantigens of the central nervous system (CNS) and their infiltration into the CNS, followed by the expansion of local and infiltrated peripheral effector myeloid cells that create an inflammatory milieu within the CNS, which ultimately lead to tissue damage and demyelination...
October 13, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29093262/human-regulatory-t-cells-undergo-self-inflicted-damage-via-granzyme-pathways-upon-activation
#20
Esilida Sula Karreci, Siawosh K Eskandari, Farokh Dotiwala, Sujit K Routray, Ahmed T Kurdi, Jean Pierre Assaker, Pavlo Luckyanchykov, Albana B Mihali, Omar Maarouf, Thiago J Borges, Abdullah Alkhudhayri, Kruti R Patel, Amr Radwan, Irene Ghobrial, Martina McGrath, Anil Chandraker, Leonardo V Riella, Wassim Elyaman, Reza Abdi, Judy Lieberman, Jamil Azzi
Tregs hold great promise as a cellular therapy for multiple immunologically mediated diseases, given their ability to control immune responses. The success of such strategies depends on the expansion of healthy, suppressive Tregs ex vivo and in vivo following the transfer. In clinical studies, levels of transferred Tregs decline sharply in the blood within a few days of the transfer. Tregs have a high rate of apoptosis. Here, we describe a new mechanism of Treg self-inflicted damage. We show that granzymes A and -B (GrA and GrB), which are highly upregulated in human Tregs upon stimulation, leak out of cytotoxic granules to induce cleavage of cytoplasmic and nuclear substrates, precipitating apoptosis in target cells...
November 2, 2017: JCI Insight
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