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T-Cell apoptosis

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https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#1
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550198/host-derived-cd70-suppresses-murine-graft-versus-host-disease-by-limiting-donor-t-cell-expansion-and-effector-function
#2
Nicholas D Leigh, Rachel E O'Neill, Wei Du, Chuan Chen, Jingxin Qiu, Jonathan D Ashwell, Philip L McCarthy, George L Chen, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expressed on T cells, and its ligand, CD70, is expressed on APCs. The CD27/CD70 costimulatory pathway was shown to be critical for T cell function and survival in viral infection models...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550122/the-blood-borne-sialyltransferase-st6gal-1-is-a-negative-systemic-regulator-of-granulopoiesis
#3
Christopher W L Dougher, Alexander Buffone, Michael J Nemeth, Mehrab Nasirikenari, Eric E Irons, Paul N Bogner, Joseph T Y Lau
Responding to systemic demands in producing and replenishing end-effector blood cells is predicated on the appropriate delivery and interpretation of extrinsic signals to the HSPCs. The data presented herein implicate the systemic, extracellular form of the glycosyltransferase ST6Gal-1 in the regulation of late-stage neutrophil development. ST6Gal-1 is typically a membrane-bound enzyme sequestered within the intracellular secretory apparatus, but an extracellular form is released into the blood from the liver...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28549559/the-novel-indole-3-formaldehyde-2-aitfei-3-f-is-involved-in-processes-of-apoptosis-induction
#4
Mojgan Noroozi Karimabad, Mehdi Mahmoodi, Abdollah Jafarzadeh, Ali Darehkordi, Mohammad Reza Hajizadeh, Hossein Khorramdelazad, Soudeh Khanamani Falahati-Pour, Gholamhossein Hassanshahi
AIM AND OBJECTIVES: Balancing between Bax and Bcl-2 plays critical roles in both proliferation and self-renewal activation of cancer cells. Indole-3-formaldehyde derivatives limit the growth and facilitate cell death in different cell systems. In this study, we introduced a novel indole derivative (2-AITFEI-3-F) with tendency to facilitate apoptosis in NB4 line in comparison to basal Indole-3-formaldehyde (I3F). METHODS: The NB4 cells were cultured in RPMI1640 medium contained 2-AITFEI-3-F and I3F (15...
May 23, 2017: Life Sciences
https://www.readbyqxmd.com/read/28549491/increased-chondrocyte-apoptosis-in-kashin-beck-disease-and-rats-induced-by-t-2-toxin-and-selenium-deficiency
#5
Hao Jie Yang, Ying Zhang, Zhi Lun Wang, Sen Hai Xue, Si Yuan Li, Xiao Rong Zhou, Meng ZHANGg, Qian Fang, Wen Jun Wang, Chen Chen, Xiang Hua Deng, Jing Hong Chen
OBJECTIVE: To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease (KBD) and in an established T-2 toxin- and selenium (Se) deficiency-induced rat model. METHODS: Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining...
May 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28549200/effects-of-cell-death-inducing-dff45-like-effector-b-on-meat-quality-traits-in-berkshire-pigs
#6
G E Yu, S Kwon, J H Hwang, S M An, D H Park, D G Kang, T W Kim, I-S Kim, H C Park, J Ha, C W Kim
Cell death-inducing DFF45-like effector (CIDE) B is a member of the CIDE family of apoptosis-inducing factors. In the present study, we detected a single nucleotide polymorphism (SNP), c.414G>A, which corresponds to the synonymous SNP 414Arg, in CIDE-B in the Berkshire pigs. We also analyzed the relationships between the CIDE-B SNP and various meat quality traits. The SNP was significantly associated with post-mortem pH24h, water-holding capacity (WHC), fat content, protein content, drip loss, post-mortem temperature at 12 h (T12) and 24 h (T24) in a co-dominant model (P < 0...
May 25, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28548945/soluble-antigens-from-the-neurotropic-pathogen-angiostrongylus-cantonensis-directly-induce-thymus-atrophy-in-a-mouse-model
#7
Zhen Liu, Dong-Ming Su, Zi-Long Yu, Feng Wu, Rui-Feng Liu, Shi-Qi Luo, Zhi-Yue Lv, Xin Zeng, Xi Sun, Zhong-Dao Wu
The nematode Angiostrongylus cantonensis (A.C.) is a neurotropic pathogen; stage-III larva invade the human (non-permissive host) central nervous system (CNS) to cause eosinophilic meningitis or meningoencephalitis accompanied by immunosuppression. In an A.C.-infectedmouse (another non-permissive host) model, CNS damage-associated T cell immune deficiency and severe inflammation were proposed to result from activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, glucocorticoids are anti-inflammatory agents...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548942/the-n-terminal-tail-coordinates-with-carbohydrate-recognition-domain-to-mediate-galectin-3-induced-apoptosis-in-t-cells
#8
Huiting Xue, Lu Liu, Zihan Zhao, Zhongyu Zhang, Yuan Guan, Hairong Cheng, Yifa Zhou, Guihua Tai
Galectin-3 is a galectin with a unique flexible N-terminal tail (NT) connected to the conserved carbohydrate recognition domain (CRD). Galectin-3 is associated with tumor immune tolerance and exhibits an ability to induce T cell apoptosis. We used Jurkat, Jurkat E6-1 and CEM T-cell lines and human peripheral blood mononuclear cells (PBMCs) to investigate the specific roles of the CRD and NT in inducing T cell apoptosis. Galectin-3 triggered sustained extracellular signal-regulated kinase (ERK) phosphorylation that induced apoptosis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548645/waldenstrom-macroglobulinemia-cells-devoid-of-btk-c481s-or-cxcr4-whim-like-mutations-acquire-resistance-to-ibrutinib-through-upregulation-of-bcl-2-and-akt-resulting-in-vulnerability-towards-venetoclax-or-mk2206-treatment
#9
A Paulus, S Akhtar, H Yousaf, A Manna, S M Paulus, Y Bashir, T R Caulfield, M Kuranz-Blake, K Chitta, X Wang, Y Asmann, R Hudec, W Springer, S Ailawadhi, A Chanan-Khan
Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9-3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed the absence of BTK(C481S) and CXCR4(WHIM-like) mutations...
May 26, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28545032/endoplasmic-reticulum-stress-mediated-membrane-expression-of-crt-erp57-induces-immunogenic-apoptosis-in-drug-resistant-endometrial-cancer-cells
#10
Qin Xu, Chuanben Chen, An Lin, Yunqing Xie
OBJECTIVE: To investigate the role of endoplasmic reticulum (ER) stress-mediated CRT/ERp57 complex expression underlying the mechanism of resistance to doxorubicin (DOX) in endometrial carcinoma (EC) in vivo and in vitro. METHODS: The expression of CRT, ERp57, p-PERK, eIF2α, p-eIF2α in EC patients and EC cells was detected by Western blots and by immunofluorescence assay. MTT assay was used to determine the LC50 of EC cells to DOX and cell viability. Apoptosis was assayed using flow cytometer...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544747/k-ras-mutation-and-amplification-status-is-predictive-of-resistance-and-high-basal-pakt-is-predictive-of-sensitivity-to-everolimus-in-biliary-tract-cancer-cell-lines
#11
Yvonne Yeung, David K Lau, Fiona Chionh, Hoanh Tran, Janson W T Tse, Andrew J Weickhardt, Mehrdad Nikfarjam, Andrew M Scott, Niall C Tebbutt, John M Mariadason
Advanced biliary tract cancer (BTC) has a poor prognosis and limited treatment options. The PI3K/Akt/mTOR signaling pathway is hyperactivated in a subset of BTCs and clinical activity to the mTOR inhibitor everolimus has been observed in some BTC patients. The goal of this study was to identify biomarkers predictive of everolimus response. Twenty BTC cell lines were assessed for everolimus sensitivity with a spectrum of growth inhibitory responses observed. Molecular biomarkers of sensitivity and resistance were identified by interrogation of the activation status of the Ras/MAPK and PI3K/Akt/mTOR pathways...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28544542/conditional-macrophage-depletion-increases-inflammation-and-does-not-inhibit-the-development-of-osteoarthritis-in-obese-mafia-mice
#12
Chia-Lung Wu, Jenna McNeill, Kelsey Goon, Dianne Little, Kelly Kimmerling, Janet Huebner, Virginia Kraus, Farshid Guilak
OBJECTIVE: Macrophages are believed to play a critical role in the inflammation associated with the development of osteoarthritis (OA) in obesity. The objective of the study was to investigate whether short-term, systemic depletion of macrophages would mitigate OA following injury in obese mice. METHODS: CSF-1R-GFP(+) Macrophage Fas-Induced Apoptosis (MaFIA) transgenic mice that allow conditional depletion of macrophages were placed on a high-fat diet and underwent surgery to induce knee OA...
May 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28542595/antifungal-tc17-cells-are-durable-and-stable-persisting-as-long-lasting-vaccine-memory-without-plasticity-towards-ifn%C3%AE-cells
#13
Som Gowda Nanjappa, Andrew J McDermott, J Scott Fites, Kevin Galles, Marcel Wüthrich, George S Deepe, Bruce S Klein
Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542576/ebola-virus-glycoprotein-directly-triggers-t-lymphocyte-death-despite-of-the-lack-of-infection
#14
Mathieu Iampietro, Patrick Younan, Andrew Nishida, Mukta Dutta, Ndongala Michel Lubaki, Rodrigo I Santos, Richard A Koup, Michael G Katze, Alexander Bukreyev
Fatal outcomes of Ebola virus (EBOV) infections are typically preceded by a 'sepsis-like' syndrome and lymphopenia despite T cells being resistant to Ebola infection. The mechanisms that lead to T lymphocytes death remain largely unknown; however, the degree of lymphopenia is highly correlative with fatalities. Here we investigated whether the addition of EBOV or its envelope glycoprotein (GP) to isolated primary human CD4+ T cells induced cell death. We observed a significant decrease in cell viability in a GP-dependent manner, which is suggestive of a direct role of GP in T cell death...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28541776/enantioselective-apoptosis-and-oxidative-damage-induced-by-individual-isomers-of-profenofos-in-primary-hippocampal-neurons
#15
Xian T Lu, Yun Ma, Hang J Zhang, Mei Q Jin, Jun H Tang
The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L(-1). The cell viability and lactate dehydrogenase (LDH) efflux indicated that (-)-PFF exposure was associated with more toxic effects than (+)-PFF above the concentration of 5 mg L(-1) (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L(-1) (-)-PFF, (+)-PFF and rac-PFF for 24 h reached 23...
May 25, 2017: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
https://www.readbyqxmd.com/read/28540322/targeting-wnt-%C3%AE-catenin-activated-cells-with-dominant-negative-n-cadherin-to-reduce-neointima-formation
#16
Sarah Hulin-Curtis, Helen Williams, Kerry S Wadey, Graciela B Sala-Newby, Sarah J George
Approximately 50% of coronary artery bypass grafts using the autologous saphenous vein fail within 10 years due to intimal thickening. This study examined whether a gene therapy approach that selectively kills Wnt/β-catenin/T cell factor (TCF) activated vascular smooth muscle cells (VSMCs) using dominant-negative N-cadherin (dn-N-cadherin) reduced intimal thickening. Cultured human VSMCs infected with an adenovirus (Ad) encoding dn-N-cadherin via the TCF promoter (Ad-TOP-dn-N-cadherin) specifically expressed dn-N-cadherin in response to activation of the Wnt/β-catenin/TCF pathway...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28540184/detection-of-intramyocardially-injected-dir-labeled-mesenchymal-stem-cells-by-optical-and-optoacoustic-tomography
#17
Markus T Berninger, Pouyan Mohajerani, Moritz Wildgruber, Nicolas Beziere, Melanie A Kimm, Xiaopeng Ma, Bernhard Haller, Megan J Fleming, Stephan Vogt, Martina Anton, Andreas B Imhoff, Vasilis Ntziachristos, Reinhard Meier, Tobias D Henning
The distribution of intramyocardially injected rabbit MSCs, labeled with the near-infrared dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbo-cyanine-iodide (DiR) using hybrid Fluorescence Molecular Tomography-X-ray Computed Tomography (FMT-XCT) and Multispectral Optoacoustic Tomography (MSOT) imaging technologies, was investigated. Viability and induction of apoptosis of DiR labeled MSCs were assessed by XTT- and Caspase-3/-7-testing in vitro. 2 × 10(6), 2 × 10(5) and 2 × 10(4) MSCs labeled with 5 and 10 μg DiR/ml were injected into fresh frozen rabbit hearts...
June 2017: Photoacoustics
https://www.readbyqxmd.com/read/28539593/identification-of-the-matricellular-protein-fibulin-5-as-a-target-molecule-of-glucokinase-mediated-calcineurin-nfat-signaling-in-pancreatic-islets
#18
Tomoko Okuyama, Jun Shirakawa, Hiromi Yanagisawa, Mayu Kyohara, Shunsuke Yamazaki, Kazuki Tajima, Yu Togashi, Yasuo Terauchi
Glucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The islet Fbln5 expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase in Fbln5 expression was diminished in Irs-2-deficient islets...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539588/cooperation-of-oncolytic-herpes-virotherapy-and-pd-1-blockade-in-murine-rhabdomyosarcoma-models
#19
Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M Swain, Julia K Love, Joseph R Stanek, Louis Boon, Joe Conner, Timothy P Cripe
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28537927/wx-132-18b-a-novel-microtubule-inhibitor-exhibits-promising-anti-tumor-effects
#20
Fang Guan, Rui Ding, Qi Zhang, Wei Chen, Feifei Li, Long Long, Wei Li, Linna Li, Dexuan Yang, Lan Xie, Shoujun Yuan, Lili Wang
Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance...
May 9, 2017: Oncotarget
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