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Immune modulation

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https://www.readbyqxmd.com/read/28719615/a-human-tissue-based-functional-assay-platform-to-evaluate-the-immune-function-impact-of-small-molecule-inhibitors-that-target-the-immune-system
#1
Cristina St Pierre, Jane Guo, John D Shin, Laura W Engstrom, Hyun-Hee Lee, Alan Herbert, Laura Surdi, James Baker, Michael Salmon, Sanjiv Shah, J Michael Ellis, Hani Houshyar, Michael A Crackower, Melanie A Kleinschek, Dallas C Jones, Alexandra Hicks, Dennis M Zaller, Stephen E Alves, Ravisankar A Ramadas
While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#2
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28719385/prevention-of-hemolytic-disease-of-the-fetus-and-newborn-what-have-we-learned-from-animal-models
#3
Yoelys Cruz-Leal, Danielle Marjoram, Alan H Lazarus
PURPOSE OF REVIEW: This review aims to highlight recent advances in our understanding of how anti-red blood cell (RBC) antibodies prevent erythrocyte immunization with an emphasis on new murine models. RECENT FINDINGS: New murine models with clinically relevant human erythrocyte antigens have been used to understand the alloimmunization process and its inhibition. The search to elucidate the mechanism of action of IgG-mediated inhibition of erythrocyte alloimmunization has provided new evidence in support of a potential role for epitope masking, immune deviation and/or antigen modulation in this process...
July 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28719178/the-therapeutic-role-and-drug-delivery-potential-of-neuroinflammation-as-a-target-in-neurodegenerative-disorders
#4
Abhijeet Singh, Ankit Chokriwal, Madan Mohan Sharma, Devendra Jain, Juhi Saxena, Bjorn John Stephen
Neuroinflammation, the condition associated with the hyper activity of immune cells within the CNS (central nervous system) has recently been linked to a host range of neurodegenerative disorders. Targeting neuroinflammation could be of prime importance as recent research highlights the beneficial aspects associated with modulating the inflammatory mediators associated with the CNS. One of the main obstructions in neuroinflammatory treatments is the hindrance posed by the Blood Brain Barrier for the delivery of drugs...
July 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28718997/mesenchymal-stem-cell-derived-factors-immuno-modulatory-effects-and-therapeutic-potential
#5
REVIEW
Vladislav Volarevic, Marina Gazdic, Bojana Simovic Markovic, Nemanja Jovicic, Valentin Djonov, Nebojsa Arsenijevic
Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed...
July 18, 2017: BioFactors
https://www.readbyqxmd.com/read/28718419/targeting-pi3k-signaling-in-combination-cancer-therapy
#6
REVIEW
Elvire Pons-Tostivint, Benoît Thibault, Julie Guillermet-Guibert
Targeting upstream phosphatidylinositol-3-kinases (PI3Ks) in the PI3K/Akt/mTOR pathway appears to be a promising therapy in solid cancers; however, first early clinical trials with PI3K inhibitors in monotherapy have been disappointing. A massive array of preclinical and clinical trials are currently evaluating combinations of PI3K inhibitors in targeted therapies. These combinations include co-treatments with drugs directed against other intra-/extracellular signaling molecules, nuclear hormone receptors, DNA damage repair enzymes, and immune modulators...
June 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718351/exosomal-hsp60-a-potentially-useful-biomarker-for-diagnosis-assessing-prognosis-and-monitoring-response-to-treatment
#7
Caruso Bavisotto, F Cappello, Ajl Macario, E Conway de Macario, M Logozzi, S Fais, C Campanella
Cell-to-cell communication is imperative for life and it is mediated by sending and receiving information via the secretion and subsequent receptor-mediated detection of biological molecules. Exosomes (EXs) secreted from cells to the extracellular environment play an important role in intercellular communication in normal and pathological conditions. Areas covered: New evidence indicates that tumor cells-derived EXs contribute to cancer progression through the modulation of tumor microenvironment. The exosomal heat shock protein 60 (HSP60) is very likely a key player in intercellular cross-talk, particularly during the progress of diseases, such as cancer...
July 18, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28718331/entinostat-for-the-treatment-of-breast-cancer
#8
Dario Trapani, Angela Esposito, Carmen Criscitiello, Luca Mazzarella, Marzia Locatelli, Ida Minchella, Saverio Minucci, Giuseppe Curigliano
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results...
July 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28718031/newcomers-in-paediatric-gi-pathology-childhood-enteropathies-including-very-early-onset-monogenic-ibd
#9
Arzu Ensari, Judith Kelsen, Pierre Russo
Childhood enteropathies are a group of diseases causing severe chronic (>2-3 weeks) diarrhoea often starting in the first week of life with the potential for fatal complications for the affected infant. Early identification and accurate classification of childhood enteropathies are, therefore, crucial for making treatment decisions to prevent life-threatening complications. Childhood enteropathies are classified into four groups based on the underlying pathology: (i) conditions related to defective digestion, absorption and transport of nutrients and electrolytes; (ii) disorders related to enterocyte differentiation and polarization; (iii) defects of enteroendocrine cell differentiation; and (iv) disorders associated with defective modulation of intestinal immune response...
July 17, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#10
Tanja Vajen, Birke J Benedikter, Alexandra C A Heinzmann, Elena M Vasina, Yvonne Henskens, Martin Parsons, Patricia B Maguire, Frank R Stassen, Johan W M Heemskerk, Leon J Schurgers, Rory R Koenen
Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717403/the-potential-role-of-adult-stem-cells-in-the-management-of-the-rheumatic-diseases
#11
REVIEW
Tiziana Franceschetti, Cosimo De Bari
Adult stem cells are considered as appealing therapeutic candidates for inflammatory and degenerative musculoskeletal diseases. A large body of preclinical research has contributed to describing their immune-modulating properties and regenerative potential. Additionally, increasing evidence suggests that stem cell differentiation and function are disrupted in the pathogenesis of rheumatic diseases. Clinical studies have been limited, for the most part, to the application of adult stem cell-based treatments on small numbers of patients or as a 'salvage' therapy in life-threatening disease cases...
July 2017: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/28717181/discovery-of-novel-human-gene-regulatory-modules-from-gene-co-expression-and-promoter-motif-analysis
#12
Shisong Ma, Michael Snyder, Savithramma P Dinesh-Kumar
Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif's enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716985/two-microrna-signatures-for-malignancy-and-immune-infiltration-predict-overall-survival-in-advanced-epithelial-ovarian-cancer
#13
Ilya Korsunsky, Janaki Parameswaran, Iuliana Shapira, John Lovecchio, Andrew Menzin, Jill Whyte, Lisa Dos Santos, Sharon Liang, Tawfiqul Bhuiya, Mary Keogh, Houman Khalili, Cassandra Pond, Anthony Liew, Andrew Shih, Peter K Gregersen, Annette T Lee
MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions...
July 17, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28716899/hdac1-upregulation-by-nanog-promotes-multidrug-resistance-and-a-stem-like-phenotype-in-immune-edited-tumor-cells
#14
Kwon-Ho Song, Chel Hun Choi, Hyo-Jung Lee, Se Jin Oh, Seon Rang Woo, Soon-Oh Hong, Kyung Hee Noh, Hanbyoul Cho, Eun Joo Chung, Jae-Hoon Kim, Joon-Yong Chung, Stephen M Hewitt, Seungki Baek, Kyung-Mi Lee, Cassian Yee, Minjoo Son, Chih-Ping Mao, T-C Wu, Tae Woo Kim
Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Immunoediting driven by antigen (Ag)-specific T cells enriches NANOG expression in tumor cells, resulting in a stem-like phenotype and immune resistance. Here we identify HDAC1 as a key mediator of the NANOG-associated phenotype. NANOG upregulated HDAC1 through promoter occupancy, thereby decreasing histone H3 acetylation on K14 and K27. NANOG-dependent, HDAC1-driven epigenetic silencing of cell cycle inhibitor CDKN2D and CDKN1B induced stem-like features...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716890/negative-regulation-of-cytokine-signaling-in-immunity
#15
Akihiko Yoshimura, Minako Ito, Shunsuke Chikuma, Takashi Akanuma, Hiroko Nakatsukasa
Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of cytokine signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716827/galectin-1-driven-tolerogenic-programs-aggravate-yersinia-enterocolitica-infection-by-repressing-antibacterial-immunity
#16
Roberto C Davicino, Santiago P Méndez-Huergo, Ricardo J Eliçabe, Juan C Stupirski, Ingo Autenrieth, María S Di Genaro, Gabriel A Rabinovich
Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersinia outer proteins (Yops), that modulate activation, signaling, and survival of immune cells. In this article, we show that galectin-1 (Gal-1), an immunoregulatory lectin widely expressed in mucosal tissues, contributes to Y...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716464/modulating-effects-of-omega-3-fatty-acids-and-pioglitazone-combination-on-insulin-resistance-through-toll-like-receptor-4-in-type-2-diabetes-mellitus
#17
Salma M Eraky, Noha Abdel-Rahman, Laila A Eissa
Toll-like receptor 4 (TLR-4) plays important roles in innate immunity. Changes in the reduction-oxidation balance of tissues can lead to a pro-inflammatory state and insulin resistance. An action thought to be mediated by TLRs. Omega-3 fatty acids and Peroxisome Proliferator Activated Receptor gamma (PPAR-γ) agonists as pioglitazone are used for decreasing inflammation. The aim of this study is to investigate the anti-diabetic effects of combining omega -3 fatty acid with pioglitazone on type 2 diabetes, and the modifying effects on TLR-4...
June 17, 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28716092/the-role-of-microglial-p2x7-modulation-of-cell-death-and-cytokine-release
#18
Yingbo He, Natalie Taylor, Lawrence Fourgeaud, Anindya Bhattacharya
BACKGROUND: ATP-gated P2X7 is a non-selective cation channel, which participates in a wide range of cellular functions as well as pathophysiological processes including neuropathic pain, immune response, and neuroinflammation. Despite its abundant expression in microglia, the role of P2X7 in neuroinflammation still remains unclear. METHODS: Primary microglia were isolated from cortices of P0-2 C57BL/6 wild-type or P2X7 knockout (P2X7(-/-)) mouse pups. Lipopolysaccharide, lipopolysaccharide plus IFNγ, or IL4 plus IL13 were used to polarize microglia to pro-inflammatory or anti-inflammatory states...
July 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28715682/cath-2-and-ll-37-increase-mannose-receptor-expression-antigen-presentation-and-the-endocytic-capacity-of-chicken-mononuclear-phagocytes
#19
Marina D Kraaij, Albert van Dijk, Henk P Haagsman
Cathelicidins display in vitro and in vivo immunomodulatory activities and are part of the innate immune system. Previously, we found that in ovo treatment with chicken cathelicidin CATH-2 partially protects young broilers against respiratory E. coli infection. To determine the cellular aspects of this protection, we investigated immunomodulatory effects of CATH-2 and the human cathelicidin LL-37 on primary chicken peripheral blood mononuclear cells (PBMCs). Treatment of chicken PBMCs with L-CATH-2, D-CATH-2 or LL-37 increased the percentage of mononuclear phagocytes, but decreased that of B cells...
July 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28715645/characteristics-of-regulatory-b-cells-in-patients-with-chronic-hepatitis-b-virus-infection-in-different-immune-phases
#20
Guiyang Wang, Yong Liu, Rui Huang, Bei Jia, Ran Su, Zhenhua Sun, Chen Tian, Yali Xiong, Juan Xia, Xiaomin Yan, Zhaoping Zhang, Chao Wu
Regulatory B cells (Bregs) are reported to play an important role in the immune responses to chronic hepatitis B virus (HBV) via Toll-like-receptors (TLRs) signaling. We aimed to investigate the characteristics of Bregs and the expressions of TLRs in Bregs in the peripheral blood of different immune phases of patients with chronic HBV infection. In this study, we determined the frequencies of Bregs and TLR9, TLR2, and TLR4 in peripheral blood using flow cytometry and determined the levels of IL-10 in serum with the Human Magnetic Cytokine/Chemokine Bead Panel...
May 2017: Discovery Medicine
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