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https://www.readbyqxmd.com/read/29679542/treatments-for-diabetes-mellitus-type-ii-new-perspectives-regarding-the-possible-role-of-calcium-and-camp-interaction
#1
REVIEW
Diego Soares Carvalho, Alexandre Aparecido de Almeida, Aurélio Ferreira Borges, Diego Vannucci Campos
Diabetes mellitus (DM) is among the top ten causes of death worldwide. It is considered to be one of the major global epidemics of the 21st century, with a significant impact on public health budgets. DM is a metabolic disorder with multiple etiologies. Its pathophysiology is marked by dysfunction of pancreatic β-cells which compromises the synthesis and secretion of insulin along with resistance to insulin action in peripheral tissues (muscle and adipose). Subjects presenting insulin resistance in DM type 2 often also exhibit increased insulin secretion and hyperinsulinemia...
April 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29679299/impact-of-computer-aided-ct-and-pet-analysis-on-non-invasive-t-staging-in-patients-with-lung-cancer-and-atelectasis
#2
Paul Flechsig, Ramin Rastgoo, Clemens Kratochwil, Ole Martin, Tim Holland-Letz, Alexander Harms, Hans-Ulrich Kauczor, Uwe Haberkorn, Frederik L Giesel
PURPOSE: Tumor delineation within an atelectasis in lung cancer patients is not always accurate. When T staging is done by integrated 2-deoxy-2-[18 F]fluoro-D-glucose ([18 F]FDG)-positron emission tomography (PET)/X-ray computer tomography (CT), tumors of neuroendocrine differentiation and slowly growing tumors can present with reduced FDG uptake, thus aggravating an exact T staging. In order to further exhaust information derived from [18 F]FDG-PET/CT, we evaluated the impact of CT density and maximum standardized uptake value (SUVmax) for the classification of different tumor subtypes within a surrounding atelectasis, as well as possible cutoff values for the differentiation between the primary tumor and atelectatic lung tissue...
April 20, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29676639/effects-of-controlled-diesel-exhaust-and-allergen-exposure-on-microrna-and-gene-expression-in-humans-modulation-of-lung-inflammatory-markers-associated-with-asthma
#3
Christopher F Rider, Masatsugu Yamamoto, Oliver P Günther, Amrit Singh, Jeremy A Hirota, Scott J Tebbutt, Christopher Carlsten
RATIONALE: Air pollution may contribute to the development of allergic diseases, including asthma, by enhancing immune responses to allergen, but the effects on microRNA, messenger RNA, and inflammatory markers remain unexplored. OBJECTIVES: To determine if acute exposure to diesel exhaust and/or allergen alters expression of microRNA and genes with effects on inflammatory markers associated with asthma. METHODS: Fifteen atopic participants were exposed in a crossover trial to inhaled filtered air or diesel exhaust (DE; 300 μg particulate matter with aerodynamic diameter less than or equal to 2...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29675979/senescent-cells-re-engineered-to-express-spd-1-for-inhibiting-pd-1-pd-l1-as-a-vaccination-approach-against-breast-cancer
#4
Zehong Chen, Kang Hu, Lieting Feng, Ruxiong Su, Nan Lai, Zike Yang, Shijun Kang
Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the PD-1/PD-L1 pathway was found to play an important role in vaccine failure. Hence, we further developed sPD1-expressing senescent cells to overcome PD-L1/PD1-mediated immune suppression while vaccinating to promote dendritic cells (DCs) maturity, thereby amplifying T cell activation...
April 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29674350/awakening-exhausted-nk-cells-in-lymphomas
#5
Lapo Alinari
No abstract text is available yet for this article.
April 19, 2018: Blood
https://www.readbyqxmd.com/read/29672862/aryl-hydrocarbon-receptor-activation-by-diesel-exhaust-particles-mediates-epithelium-derived-cytokines-expression-in-severe-allergic-asthma
#6
Chih-Ming Weng, Chun-Hua Wang, Meng-Jung Lee, Jung-Re He, Hsin-Yu Huang, Ming-Wei Chao, Kian Fan Chung, Han-Pin Kuo
BACKGROUND: Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium-derived thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma. METHODS: Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation (NT), cytokine expression and gene activation...
April 19, 2018: Allergy
https://www.readbyqxmd.com/read/29672594/type-i-interferon-signaling-attenuates-regulatory-t-cell-function-in-viral-infection-and-in-the-tumor-microenvironment
#7
Arunakumar Gangaplara, Craig Martens, Eric Dahlstrom, Amina Metidji, Ameya S Gokhale, Deborah D Glass, Maria Lopez-Ocasio, Rachel Baur, Kishore Kanakabandi, Stephen F Porcella, Ethan M Shevach
Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute, chronic infectious diseases and tumor microenvironment remains unclear. We recently demonstrated that IFN-α/β receptor (IFNAR) signaling promotes Treg function in autoimmunity. Here we dissected the functional role of IFNAR-signaling in Tregs using Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice in acute LCMV Armstrong, chronic Clone-13 viral infection, and in tumor models...
April 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29671161/under-evaluated-or-unassessed-pathogenic-pathways-in-autoimmune-hepatitis-and-implications-for-future-management
#8
REVIEW
Albert J Czaja
Autoimmune hepatitis is a consequence of perturbations in homeostatic mechanisms that maintain self-tolerance but are incompletely understood. The goals of this review are to describe key pathogenic pathways that have been under-evaluated or unassessed in autoimmune hepatitis, describe insights that may shape future therapies, and encourage investigational efforts. The T cell immunoglobulin mucin proteins constitute a family that modulates immune tolerance by limiting the survival of immune effector cells, clearing apoptotic bodies, and expanding the population of granulocytic myeloid-derived suppressor cells...
April 18, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29670776/-kit-d816v-positive-acute-mast-cell-leukemia-associated-with-normal-karyotype-acute-myeloid-leukemia
#9
Marta Lopes, Maria Dos Anjos Teixeira, Cláudia Casais, Vanessa Mesquita, Patrícia Seabra, Renata Cabral, José Palla-García, Catarina Lau, João Rodrigues, Maria Jara-Acevedo, Inês Freitas, Jose Ramón Vizcaíno, Jorge Coutinho, Luis Escribano, Alberto Orfao, Margarida Lima
Introduction: Mast cell (MC) leukemia (MCL) is extremely rare. We present a case of MCL diagnosed concomitantly with acute myeloblastic leukemia (AML). Case Report: A 41-year-old woman presented with asthenia, anorexia, fever, epigastralgia, and diarrhea. She had a maculopapular skin rash, hepatosplenomegaly, retroperitoneal adenopathies, pancytopenia, 6% blast cells (BC) and 20% MC in the peripheral blood, elevated lactate dehydrogenase, cholestasis, hypoalbuminemia, hypogammaglobulinemia, and increased serum tryptase (184  μ g/L)...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29670673/pm2-5-induced-the-expression-of-fibrogenic-mediators-via-hmgb1-rage-signaling-in-human-airway-epithelial-cells
#10
Weifeng Zou, Fang He, Sha Liu, Jinding Pu, Jinxing Hu, Qing Sheng, Tao Zhu, Tianhua Zhu, Bing Li, Pixin Ran
Background: The aim of the present study was to test whether fine particulate matter (PM2.5) induces the expression of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, and transforming growth factor- β 1 (TGF- β 1) in human bronchial epithelial cells (HBECs) in vitro via high-mobility group box 1 (HMGB1) receptor for advanced glycation end products (RAGE) signaling. Methods: Sprague-Dawley rats were exposed to motor vehicle exhaust (MVE) or clean air. HBECs were either transfected with a small interfering RNA (siRNA) targeting HMGB1 or incubated with anti-RAGE antibodies and subsequently stimulated with PM2...
2018: Canadian Respiratory Journal: Journal of the Canadian Thoracic Society
https://www.readbyqxmd.com/read/29670207/homeostatic-proliferation-leads-to-telomere-attrition-and-increased-pd-1-expression-after-autologous-hematopoietic-sct-for-systemic-sclerosis
#11
Lucas C M Arruda, João R Lima-Júnior, Emmanuel Clave, Daniela A Moraes, Corinne Douay, Isabelle Fournier, Hélène Moins-Teisserenc, Dimas T Covas, Belinda P Simões, Dominique Farge, Antoine Toubert, Kelen C R Malmegrim, Maria Carolina Oliveira
In the months that follow autologous hematopoietic stem cell transplantation (AHSCT), lymphopenia drives homeostatic proliferation, leading to oligoclonal expansion of residual cells. Here we evaluated how replicative senescent and exhausted cells associated with clinical outcomes of 25 systemic sclerosis (SSc) patients who underwent AHSCT. Patients were clinically monitored for skin (modified Rodnan's skin score, mRSS) and internal organ involvement and had blood samples collected before and semiannually, until 3 years post-AHSCT, for quantification of telomere length, CD8+ CD28- and PD-1+ cells, and serum cytokines...
April 18, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29669930/tsc2-deficient-tumors-have-evidence-of-t-cell-exhaustion-and-respond-to-anti-pd-1-anti-ctla-4-immunotherapy
#12
Heng-Jia Liu, Patrick H Lizotte, Heng Du, Maria C Speranza, Hilaire C Lam, Spencer Vaughan, Nicola Alesi, Kwok-Kin Wong, Gordon J Freeman, Arlene H Sharpe, Elizabeth P Henske
Tuberous sclerosis complex (TSC) is an incurable multisystem disease characterized by mTORC1-hyperactive tumors. TSC1/2 mutations also occur in other neoplastic disorders, including lymphangioleiomyomatosis (LAM) and bladder cancer. Whether TSC-associated tumors will respond to immunotherapy is unknown. We report here that the programmed death 1 coinhibitory receptor (PD-1) is upregulated on T cells in renal angiomyolipomas (AML) and pulmonary lymphangioleiomyomatosis (LAM). In C57BL/6J mice injected with syngeneic TSC2-deficient cells, anti-PD-1 alone decreased 105K tumor growth by 67% (P < 0...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29669251/self-renewal-and-toll-like-receptor-signaling-sustain-exhausted-plasmacytoid-dendritic-cells-during-chronic-viral-infection
#13
Monica Macal, Yeara Jo, Simone Dallari, Aaron Y Chang, Jihong Dai, Shobha Swaminathan, Ellen J Wehrens, Patricia Fitzgerald-Bocarsly, Elina I Zúñiga
Although characterization of T cell exhaustion has unlocked powerful immunotherapies, the mechanisms sustaining adaptations of short-lived innate cells to chronic inflammatory settings remain unknown. During murine chronic viral infection, we found that concerted events in bone marrow and spleen mediated by type I interferon (IFN-I) and Toll-like receptor 7 (TLR7) maintained a pool of functionally exhausted plasmacytoid dendritic cells (pDCs). In the bone marrow, IFN-I compromised the number and the developmental capacity of pDC progenitors, which generated dysfunctional pDCs...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29666149/genetic-and-phenotypic-difference-in-cd8-t-cell-exhaustion-between-chronic-hepatitis-b-infection-and-hepatocellular-carcinoma
#14
Xiaochen Wang, Qifeng He, Haiyuan Shen, Xiao-Jie Lu, Beicheng Sun
BACKGROUND: Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8+ T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). METHODS: In this study, we assayed the phenotypes and functional states of CD8+ T cells separating from human CHB tissues and HCC tissues, and re-analyse the single-cell sequencing data (GSE98638) published previously...
April 17, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29664577/the-gradual-rise-of-memory-inflation
#15
REVIEW
Paul Klenerman
Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8+ T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to "exhaustion" the repeated antigen encounters experienced by CD8+ T cells lead to development of a robust T-cell population structure which maintains functionality and size...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29663369/specific-blockade-cd73-alters-the-exhausted-phenotype-of-t-cells-in-head-and-neck-squamous-cell-carcinoma
#16
Wei-Wei Deng, Yi-Cun Li, Si-Rui Ma, Liang Mao, Guang-Tao Yu, Lin-Lin Bu, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
The adenosine-induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto-5-nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4+ and CD8+ T cells was associated with an 'exhausted' phenotype. Further, treatment with anti-CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the 'exhausted' phenotype of CD4+ and CD8+ T cells through downregulation of total expression of PD-1 and CTLA-4 on T cells...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#17
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29661225/lymphocyte-subset-expression-and-serum-concentrations-of-pd-1-pd-l1-in-sepsis-pilot-study
#18
Julie K Wilson, Yuan Zhao, Mervyn Singer, Jo Spencer, Manu Shankar-Hari
BACKGROUND: Sepsis remains a major cause of mortality in critical care, for which specific treatments are lacking. The dysregulated response to infection seen in sepsis includes features of lymphocyte dysfunction and exhaustion, suggesting that immune-stimulatory therapy may improve outcomes in certain patient groups. Monoclonal antibodies targeting checkpoint molecules, such as programmed-death 1 protein (PD-1) and its ligand PD-L1, have shown success in stimulating the immune response in patients with cancer, and are being considered for future sepsis trials...
April 17, 2018: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29660158/cutaneous-presentation-preceding-acute-myeloid-leukemic-with-cd4-cd56-expression-misdiagnosed-as-a-blastic-plasmocytoid-dendritic-cell-neoplasm-a-case-report
#19
Vanessa Szablewski, Valérie Costes, Caroline Bret, Olivier Dereure, Hicheri Yosr, Melissa Alame, Valère Cacheux
Acute myeloid leukemia (AML) may initially present as cutaneous lesions corresponding to blasts involving the skin as the first clinical manifestation prior to blood and bone marrow (BM) infiltration. Such presentation is known as myeloid leukemia cutis (LC). Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is an aggressive tumour derived from the precursors of plasmocytoid dendritic cells with cutaneous and bone marrow (BM) involvement and leukemic dissemination. Myeloid LC and BPDCN may be difficult to distinguish as they share similar clinical and histopathological features, in particular AML with monocytic differentiation...
April 16, 2018: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29657294/rare-splice-variants-in-long-non-coding-rnas
#20
Rituparno Sen, Gero Doose, Peter F Stadler
Long non-coding RNAs (lncRNAs) form a substantial component of the transcriptome and are involved in a wide variety of regulatory mechanisms. Compared to protein-coding genes, they are often expressed at low levels and are restricted to a narrow range of cell types or developmental stages. As a consequence, the diversity of their isoforms is still far from being recorded and catalogued in its entirety, and the debate is ongoing about what fraction of non-coding RNAs truly conveys biological function rather than being "junk"...
July 5, 2017: Non-Coding RNA
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