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Immunological pathways

Iêda Maria Martinez Paino, Fabrício Santos, Valtencir Zucolotto
Graphene Oxide (GO) has received enormous attention regarding its possible applications in medical areas including cancer treatment. Nevertheless, graphene biocompatibility and its interactions with cancer, normal and immune system cells still remain a major issue. In the current study, we focused on the immunological impact of GO in the oxidative burst by GO produced in fresh isolated primary human neutrophils, the most abundant leukocyte of immune system. We also studied the GO cytotoxicity, cell uptake and genotoxicity in fresh isolated primary human monocyte, neutrophil, human carcinoma cervical (HeLa) and L929 cells...
October 22, 2016: Journal of Biomedical Materials Research. Part A
Naoshi Nishida, Masatoshi Kudo
Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of patients with advanced stage of disease remains unfavorable. Several immune therapies have been applied to HCC, and their responses have not been satisfactory. The immune response to cancer is determined by the balance between the antigenicity of the tumor and the microenvironment of cancer tissues. Generally, accumulated genetic mutations are observed in HCC, which may lead to increased neoantigens on cancer cells with high antigenicity...
October 21, 2016: Oncology
Suprithi Choudhary, Ashish Mourya, Swati Ahuja, Sangeeta Pilkhwal Sah, Anil Kumar
Stress is associated with many diseases and dysfunctions, such as depression, cardiovascular alterations, immunological function disorder, inflammation, obesity, and insulin resistance. Stress-induced inflammation is associated with the genesis of insulin resistance. Stress activates hypothalamic pituitary adrenal axis, Renin Angiotensin System pathway, and sympatho-adrenal system, all of which are involved in the production of cytokines, causing the negative downregulation of insulin signaling either by phosphorylating serine residues of IRS or by inhibiting the activity of Akt leading to insulin resistance...
October 19, 2016: Inflammopharmacology
Jonatan Enk, Assi Levi, Yiska Weisblum, Rachel Yamin, Yoav Charpak-Amikam, Dana G Wolf, Ofer Mandelboim
Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring...
October 18, 2016: Cell Reports
Madhavan Nair, Vidya Sagar, Sudheesh Pilakka-Kanthikeel
Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection...
October 19, 2016: Scientific Reports
Xiaopeng Zhu, Hua Bian, Xin Gao
Nonalcoholic fatty liver disease (NAFLD) is a globally observed metabolic disease with high prevalence both in adults and children. However, there is no efficient medication available yet. Increased evidence indicates that berberine (BBR), a natural plant product, has beneficial effects on NAFLD, though the mechanisms are not completely known. In this review, we briefly summarize the pathogenesis of NAFLD and factors that influence the progression of NAFLD, and focus on the potential mechanisms of BBR in the treatment of NAFLD...
October 14, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Huiting Su, Ning Na, Xiaodong Zhang, Yong Zhao
CD74 (MHC class II invariant chain, Ii) is a non-polymorphic type II transmembrane glycoprotein. It is clear that, in addition to be an MHC class II chaperone, CD74 has a diversity of biological functions in physiological and pathological situations. CD74 also participates in other non-MHC II protein trafficking, such as angiotensin II type I receptor. In addition, CD74 is a cell membrane high-affinity receptor for macrophage migration inhibitory factor (MIF), D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins...
October 17, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Christian Brigolin, Nathan McKenty, Kirit Pindolia, Barry Wolf
Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous abnormalities. Untreated individuals with biotinidase deficiency cannot recycle biotin from biocytin (N-biotinyl-ϵ-lysine), the proteolytic digestion product of protein-bound biotin. Biotin therapy can markedly resolve symptoms, or can prevent the development of symptoms if initiated early. To understand better the pathogenesis of the neurological problems in the disorder in humans, we have compared gene transcription changes during the first week post-birth in the brains of biotinidase-deficient, transgenic, knock-out mice at days 1 and 8 and compared to changes in wildtype mice at the same times...
December 2016: Molecular Genetics and Metabolism Reports
Pavitra Ramachandran, Vivian Lee, Zhangyong Wei, Ji Yun Song, Giulia Casal, Therese Cronin, Keirnan Willett, Rachel Huckfeldt, Jessica I W Morgan, Tomas S Aleman, Albert M Maguire, Jean Bennett
Within the next decade, we will see many gene therapy clinical trials for eye diseases progress, which may lead to treatments for thousands of visually impaired people around the world. To target retinal diseases that affect specific cell types, several recombinant adeno-associated virus (AAV) serotypes have been generated and used successfully in pre-clinical mouse studies. Because there are numerous anatomic, and physiologic differences between the eyes of mice and 'men' and because surgical delivery approaches and immunologic responses also differ between these species, we evaluated the transduction characteristics of two promising new serotypes AAV7m8 and AAV8BP2, in retinas of animals that are most similar to those of humans: non-human primates (NHPs)...
October 18, 2016: Human Gene Therapy
Elena W Y Hsieh, Joseph D Hernandez
PURPOSE OF REVIEW: This review gives an overview of the systems-immunology single-cell proteomic and transcriptomic approaches that can be applied to study primary immunodeficiency. It also introduces recent advances in multiparameter tissue imaging, which allows extensive immune phenotyping in disease-affected tissue. RECENT FINDINGS: Mass cytometry is a variation of flow cytometry that uses rare earth metal isotopes instead of fluorophores as tags bound to antibodies, allowing simultaneous measurement of over 40 parameters per single-cell...
October 5, 2016: Current Opinion in Allergy and Clinical Immunology
Shai S Shen-Orr, David Furman, Brian A Kidd, Francois Hadad, Patricia Lovelace, Ying-Wen Huang, Yael Rosenberg-Hasson, Sally Mackey, Fatemeh A Gomari Grisar, Yishai Pickman, Holden T Maecker, Yueh-Hsiu Chien, Cornelia L Dekker, Joseph C Wu, Atul J Butte, Mark M Davis
Chronic inflammation, a decline in immune responsiveness, and reduced cardiovascular function are all associated with aging, but the relationships among these phenomena remain unclear. Here, we longitudinally profiled a total of 84 signaling conditions in 91 young and older adults and observed an age-related reduction in cytokine responsiveness within four immune cell lineages, most prominently T cells. The phenotype can be partially explained by elevated baseline levels of phosphorylated STAT (pSTAT) proteins and a different response capacity of naive versus memory T cell subsets to interleukin 6 (IL-6), interferon α (IFN-α), and, to a lesser extent, IL-21 and IFN-γ...
October 12, 2016: Cell Systems
Wenting Ma, Le Tao, Xuefei Wang, Qinyi Liu, Wei Zhang, Qiuying Li, Chunfeng He, Dongying Xue, Jie Zhang, Cheng Liu
AIMS: Sorafenib, which has been used extensively for the treatment of renal cell cancer and advanced hepatocellular carcinoma (HCC), has also been shown to have antifibrotic effects in liver fibrosis. However, the effects of sorafenib on renal fibrosis are unknown. Therefore, we investigated whether sorafenib inhibited renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and further explored the potential mechanism. METHODS: Mice underwent UUO followed by vehicle or sorafenib treatment...
October 17, 2016: Cellular Physiology and Biochemistry
Hector R Martínez, César E Escamilla-Ocañas, Juan Miguel Tenorio-Pedraza, David Gómez-Almaguer, Jose Carlos Jaime-Perez, Leticia A Olguín-Ramírez, Sergio Salazar-Marioni, María Teresa González-Garza
INTRODUCTION: Increased cytokine expression is a prominent finding in amyotrophic lateral sclerosis (ALS). Due to their interdependence and pleiotropism, interpretation of CSF concentrations of a single cytokine is challenging. We describe a cytokine analysis in ALS patients using a pathway-based statistical method to identify changes in the whole cytokine network. METHODS: We analyzed 19 cytokines in CSF of ALS patients and controls. An equality of concentration matrices was conducted that allowed us to evaluate disturbances in the relationship of cytokines between controls and ALS patients with less and more than 12months of disease length...
October 11, 2016: Cytokine
Matthew R Collinson-Pautz, Kevin M Slawin, Jonathan M Levitt, David M Spencer
Therapeutic DNA-based vaccines aim to prime an adaptive host immune response against tumor-associated antigens, eliminating cancer cells primarily through CD8+ cytotoxic T cell-mediated destruction. To be optimally effective, immunological adjuvants are required for the activation of tumor-specific CD8+ T cells responses by DNA vaccination. Here, we describe enhanced anti-tumor efficacy of an in vivo electroporation-delivered DNA vaccine by inclusion of a genetically encoded chimeric MyD88/CD40 (MC) adjuvant, which integrates both innate and adaptive immune signaling pathways...
2016: PloS One
Rahul Krishnan, David Ko, Clarence E Foster, Wendy Liu, A M Smink, Bart de Haan, Paul De Vos, Jonathan R T Lakey
Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves...
2017: Methods in Molecular Biology
Sirilaksana Kunjara, Patricia McLean, Laurens Rademacher, Thomas W Rademacher, Fabiana Fascilla, Stefano Bettocchi, Marco Scioscia
Immunological alterations, endothelial dysfunction, and insulin resistance characterize preeclampsia. Endothelial cells hold the key role in the pathogenesis of this disease. The signaling pathways mediating these biological abnormalities converge on PKB/Akt, an intracellular kinase regulating cell survival, proliferation, and metabolism. Inositol second messengers are involved in metabolic and cell signaling pathways and are highly expressed during preeclampsia. Intracellular action of these molecules is deeply affected by zinc, manganese, and calcium...
2016: International Journal of Endocrinology
Thomas Dörner, Peter E Lipsky
New insights into the mechanisms of autoimmune diseases have been obtained not only from preclinical studies, but also from clinical trials of pan-B-cell-directed therapy. Overall, the results of these clinical trials suggest that more-specific approaches focusing on pathogenic B-cell functions, and perhaps sparing or even enhancing regulatory B-cell activity, might be attractive alternatives. Importantly, pathogenic B-cell subpopulations function within a network of cellular interactions, many of which might require additional interventions to restore immunologic balance and suppress autoimmune disease...
October 13, 2016: Nature Reviews. Rheumatology
A Sheih, W C Parks, S F Ziegler
Airway epithelial cells are among the first to encounter inhaled allergens and can initiate allergic responses by producing pro-Th2 innate cytokines. In this study, we investigated the role of epithelial-derived cytokines in sensitization to a clinically relevant allergen, cockroach allergen (CRA). Among the epithelial-derived cytokines, granulocyte macrophage colony-stimulating factor (GM-CSF) had a central role in the initiation of Th2 allergic responses to CRA. We show that initial exposure to CRA directly activated airway epithelial cells through a TLR4-MyD88-dependent pathway and MyD88 signaling in epithelial cells induced upregulation of GM-CSF during sensitization...
October 12, 2016: Mucosal Immunology
S Kang, C Zhang, T Ohno, M Azuma
The PD-1/B7-H1 pathway regulates immune responses and maintains homeostasis. Here, we identified a unique expression of B7 homolog 1 (B7-H1) on masticatory mucosae in the oral cavity. B7-H1 was physiologically expressed on the dorsal surface of the tongue, gingiva, and hard palate. Other squamous epithelia and other structures of the epithelia did not express B7-H1 in the steady state. Physiological B7-H1 expression on masticatory mucosae was limited on prickle cells, and its expression on basal keratinocytes (KCs) was strictly regulated...
October 12, 2016: Mucosal Immunology
Herman Waldmann, Duncan Howie, Stephen Cobbold
A major goal of immunosuppressive therapies is to harness immune tolerance mechanisms so as to minimize unwanted side effects associated with protracted immunosuppressive therapy. Antibody blockade of lymphocyte coreceptor and costimulatory pathways in mice has demonstrated the principle that both naive and primed immune systems can be reprogrammed toward immunological tolerance. Such tolerance can involve the amplification of activity of regulatory T cells, and is maintained through continuous recruitment of such cells through processes of infectious tolerance...
August 2016: Microbiology Spectrum
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