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https://www.readbyqxmd.com/read/28102734/fibroblast-like-synoviocytes-dependent-effector-molecules-as-a-critical-mediator-for-rheumatoid-arthritis-current-status-and-future-directions
#1
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. Currently available biological agents and inhibitor therapy that specifically target tumor necrosis factor-α, interleukin 1β (IL-1β), IL-6, T cells, B cells, and subcellular molecules (p38 mitogen-activated protein kinase and janus kinase) cannot facilitate complete remission in all patients and are unable to cure the disease. Therefore, further potent therapeutic targets need to be identified for effective treatment and successful clinical outcomes in patients with RA...
January 19, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28102226/chronic-lymphocytic-leukaemia
#2
Thomas J Kipps, Freda K Stevenson, Catherine J Wu, Carlo M Croce, Graham Packham, William G Wierda, Susan O'Brien, John Gribben, Kanti Rai
Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5(+) B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all...
January 19, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28102026/piperine-a-pungent-alkaloid-from-black-pepper-inhibits-b-lymphocyte-activation-and-effector-functions
#3
David A Soutar, Carolyn D Doucette, Robert S Liwski, David W Hoskin
Piperine has several well-documented anti-inflammatory properties; however, little is known regarding its effect on humoral immunity. In this study, we describe the immunosuppressive effect of piperine on B lymphocytes, which are integral to the humoral immune response. Mouse B cells were cultured in the absence or presence of non-cytotoxic concentrations (25, 50, and 100 μM) of piperine during T-dependent or T-independent stimulation. Piperine inhibited B cell proliferation by causing G0/G1 phase cell cycle arrest in association with reduced expression of cyclin D2 and D3...
January 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28101891/different-expression-of-leptin-and-igf1-in-the-adult-and-prepubertal-testis-in-dogs
#4
L Müller, M P Kowalewski, I M Reichler, E Kollár, O Balogh
Leptin (Lep) and insulin-like growth factor 1 (IGF1) are implicated in the regulation of testicular function, but in dogs, our knowledge is limited to the possible role of the IGF1 system in testicular tumours. In this study, we aimed to describe and compare gene expression and protein localization of Lep, IGF1 and their receptors (LepR and IGF1R, respectively) in the testis of healthy adult and prepubertal dogs. Testes were collected from sexually healthy mature (n = 7) and from 8-week-old dogs (n = 7)...
January 18, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28101786/evaluation-of-t-regulatory-lymphocytes-transcription-factors-in-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp-patients
#5
Sanaz Ahmadi Ghezeldasht, Hamed Sadeghian, Mahmoud Reza Azarpazhooh, Seyyed Ali Akbar Shamsian, Houshang Rafatpanah, Mahmood Mahmoodi, Seyyed Abdolrahim Rezaee
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4(+)CD25(+) T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 (Foxp3), and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry...
January 18, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28101221/a-complex-translocation-3-17-15-in-acute-promyelocytic-leukemia-confirmed-by-fluorescence-in-situ-hybridization
#6
Yanming Wang, Junjie Ma, Xinguang Liu, Riming Liu, Lingling Xu, Li Wang, Jiannong Cen, Xiaoxia Chu
Acute promyelocytic leukemia (APL) is typified by t(15;17)(q22;q21), generating the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The PML-RARA fusion gene is believed to play a vital role in leukemogenesis. A sizeable minority of patients with complex variants of APL have been reported. The present study reports the case of a 33-year-old male with APL carrying a potential complex translocation. The initial symptom was bleeding gums. Chromosomal analysis of the bone marrow cells revealed an atypical 17q aberration...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100849/the-role-genes-encoding-of-killer-cell-immunoglobulin-like-receptors-kirs-and-their-ligands-in-susceptibility-to-and-progression-of-hiv-infection
#7
Olga Błachowicz, Katarzyna Zwolińska
NK cells are a part of the innate antiviral response. Their activity is regulated by signals from the surface receptors. Some of them, known as killer cell immunoglobulin-like receptors (KIRs), determine the quality and intensity of the immunological response, together with their ligands (HLA class I). KIR genes are very polymorphic, and this is reflected in the NK activity modulation. The stimulation of NK cells, especially in the early stages of the infection, can reduce the transmission of HIV or slow down the progression of infection...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100838/car-t-cells-engage-in-anticancer-martial-arts
#8
Saar Gill
A clever redesign of the chimeric antigen receptor T cell concept turns a cancer-mediated immunosuppressive cytokine into a growth signal.
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100832/reporter-gene-imaging-of-targeted-t-cell-immunotherapy-in-recurrent-glioma
#9
Khun Visith Keu, Timothy H Witney, Shahriar Yaghoubi, Jarrett Rosenberg, Anita Kurien, Rachel Magnusson, John Williams, Frezghi Habte, Jamie R Wagner, Stephen Forman, Christine Brown, Martin Allen-Auerbach, Johannes Czernin, Winson Tang, Michael C Jensen, Behnam Badie, Sanjiv S Gambhir
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8(+) cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100745/disease-progression-dependent-effects-of-trem2-deficiency-in-a-mouse-model-of-alzheimer-s-disease
#10
Taylor R Jay, Anna M Hirsch, Margaret L Broihier, Crystal M Miller, Lee E Neilson, Richard M Ransohoff, Bruce T Lamb, Gary E Landreth
: Neuroinflammation is an important contributor to Alzheimer's disease (AD) pathogenesis, as underscored by the recent identification of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2). Understanding TREM2 function promises to provide important insights into how neuroinflammation contributes to AD pathology. However, studies so far have produced seemingly conflicting results, with reports that amyloid pathology can be both decreased and increased in TREM2-deficient AD mouse models...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100666/t-type-ca2-channels-are-required-for-enhanced-sympathetic-axon-growth-by-tnf%C3%AE-reverse-signalling
#11
Lilian Kisiswa, Clara Erice, Laurent Ferron, Sean Wyatt, Catarina Osório, Annette C Dolphin, Alun M Davies
Tumour necrosis factor receptor 1 (TNFR1)-activated TNFα reverse signalling, in which membrane-integrated TNFα functions as a receptor for TNFR1, enhances axon growth from developing sympathetic neurons and plays a crucial role in establishing sympathetic innervation. Here, we have investigated the link between TNFα reverse signalling and axon growth in cultured sympathetic neurons. TNFR1-activated TNFα reverse signalling promotes Ca(2+) influx, and highly selective T-type Ca(2+) channel inhibitors, but not pharmacological inhibitors of L-type, N-type and P/Q-type Ca(2+) channels, prevented enhanced axon growth...
January 2017: Open Biology
https://www.readbyqxmd.com/read/28100650/transforming-growth-factor-%C3%AE-suppresses-peroxisome-proliferator-activated-receptor-%C3%AE-expression-via-both-smad-binding-and-novel-tgf-%C3%AE-inhibitory-elements
#12
Sowmya P Lakshmi, Aravind T Reddy, Raju C Reddy
Transforming growth factor β (TGF-β) contributes to wound healing and, when dysregulated, to pathological fibrosis. TGF-β and the anti-fibrotic nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) repress each other's expression, and such PPARγ downregulation is prominent in fibrosis and mediated, via previously unknown mechanisms, by SMAD signaling. Here we show that TGF-β induces association of SMAD3 with both SMAD4, needed for translocation of the complex into the nucleus, and the essential context-sensitive corepressors E2F4 and p107...
January 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#13
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28100033/relaxin-3-inputs-target-hippocampal-interneurons-and-deletion-of-hilar-relaxin-3-receptors-in-floxed-rxfp3-mice-impairs-spatial-memory
#14
M Haidar, G Guèvremont, C Zhang, Rad Bathgate, E Timofeeva, C M Smith, A L Gundlach
Hippocampus is innervated by γ-aminobutyric acid (GABA) 'projection' neurons of the nucleus incertus (NI), including a population expressing the neuropeptide, relaxin-3 (RLN3). In studies aimed at gaining an understanding of the role of RLN3 signaling in hippocampus via its Gi/o -protein-coupled receptor, RXFP3, we examined the distribution of RLN3-immunoreactive nerve fibres and RXFP3 mRNA-positive neurons in relation to hippocampal GABA neuron populations. RLN3-positive elements were detected in close-apposition with a substantial population of somatostatin (SST)- and GABA-immunoreactive neurons, and a smaller population of parvalbumin- and calretinin-immunoreactive neurons in different hippocampal areas, consistent with the relative distribution patterns of RXFP3 mRNA and these marker transcripts...
January 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/28099915/liquid-biopsy-genotyping-in-lung-cancer-ready-for-clinical-utility
#15
Wei-Lun Huang, Yi-Lin Chen, Szu-Chun Yang, Chung-Liang Ho, Fang Wei, David T Wong, Wu-Chou Su, Chien-Chung Lin
Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care...
January 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099848/biophysical-attributes-of-cpg-presentation-control-tlr9-signaling-to-differentially-polarize-systemic-immune-responses
#16
Jardin A Leleux, Pallab Pradhan, Krishnendu Roy
It is currently unknown whether and how mammalian pathogen recognition receptors (PRRs) respond to biophysical patterns of pathogen-associated molecular danger signals. Using synthetic pathogen-like particles (PLPs) that mimic physical properties of bacteria or large viruses, we have discovered that the quality and quantity of Toll-like receptor 9 (TLR9) signaling by CpG in mouse dendritic cells (mDCs) are uniquely dependent on biophysical attributes; specifically, the surface density of CpG and size of the presenting PLP...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099841/targeted-inhibition-of-egfr-and-glutaminase-induces-metabolic-crisis-in-egfr-mutant-lung-cancer
#17
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Clara Magyar, Daniel Braas, Thomas Graeber, Nicholas J Jackson, Johannes Czernin, Ethan Emberley, Matthew Gross, Julie Janes, Andy Mackinnon, Alison Pan, Mirna Rodriguez, Melissa Works, Winter Zhang, Francesco Parlati, Susan Demo, Edward Garon, Kostyantyn Krysan, Tonya C Walser, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099381/daily-propranolol-administration-reduces-persistent-injury-associated-anemia-following-severe-trauma-and-chronic-stress
#18
Ines G Alamo, Kolenkode B Kannan, Letitia E Bible, Tyler J Loftus, Harry Ramos, Philip A Efron, Alicia M Mohr
BACKGROUND: Following severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators such as ferroportin, transferrin and transferrin receptor-1 (TFR-1) are unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a non-selective beta-blocker, restores bone marrow function and improves iron homeostasis...
January 17, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28099204/narrowing-in-on-the-anti-%C3%AE-cell-specific-t-cells-looking-where-the-action-is
#19
Sally C Kent, Jenny Aurielle B Babon
PURPOSE OF THE REVIEW: By necessity, the vast majority of information we have on autoreactive T cells in human type 1 diabetes (T1D) has come from the study of peripheral blood of donors with T1D. It is not clear how representative the peripheral autoreactive T-cell repertoire is of the autoreactive T cells infiltrating the islets in T1D. We will summarize and discuss what is known of the immunohistopathology of insulitis, the T-cell receptor repertoire expressed by islet-infiltrating T cells, and the autoreactivity and function of islet-infiltrating T cells in T1D...
January 17, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28096694/luteolin-inhibits-lung-metastasis-cell-migration-and-viability-of-triple-negative-breast-cancer-cells
#20
Matthew T Cook, Yayun Liang, Cynthia Besch-Williford, Salman M Hyder
Most breast cancer-related deaths from triple-negative breast cancer (TNBC) occur following metastasis of cancer cells and development of tumors at secondary sites. Because TNBCs lack the three receptors targeted by current chemotherapeutic regimens, they are typically treated with extremely aggressive and highly toxic non-targeted treatment strategies. Women with TNBC frequently develop metastatic lesions originating from drug-resistant residual cells and have poor prognosis. For this reason, novel therapeutic strategies that are safer and more effective are sought...
2017: Breast Cancer: Targets and Therapy
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