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https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#1
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926930/cytomegalovirus-specific-il-10-producing-cd4-t-cells-are-governed-by-type-i-ifn-induced-il-27-and-promote-virus-persistence
#2
Mathew Clement, Morgan Marsden, Maria A Stacey, Juneid Abdul-Karim, Silvia Gimeno Brias, Diana Costa Bento, Martin J Scurr, Peter Ghazal, Casey T Weaver, Gianluca Carlesso, Simon Clare, Simon A Jones, Andrew Godkin, Gareth W Jones, Ian R Humphreys
CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#3
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926855/temporally-programmed-cd8%C3%AE-dc-activation-enhances-combination-cancer-immunotherapy
#4
Alice Tzeng, Monique J Kauke, Eric F Zhu, Kelly D Moynihan, Cary F Opel, Nicole J Yang, Naveen Mehta, Ryan L Kelly, Gregory L Szeto, Willem W Overwijk, Darrell J Irvine, K Dane Wittrup
Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α(+) dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926828/harnessing-cancer-cell-metabolism-for-theranostic-applications-using-metabolic-glycoengineering-of-sialic-acid-in-breast-cancer-as-a-pioneering-example
#5
REVIEW
Haitham A Badr, Dina M M AlSadek, Motawa E El-Houseini, Christopher T Saeui, Mohit P Mathew, Kevin J Yarema, Hafiz Ahmed
Abnormal cell surface display of sialic acids - a family of unusual 9-carbon sugars - is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation...
November 25, 2016: Biomaterials
https://www.readbyqxmd.com/read/27926504/the-immunomodulatory-effects-of-tnf-%C3%AE-inhibitors-on-human-th17-cells-via-ror%C3%AE-t-histone-acetylation
#6
Yi-Ching Lin, Yu-Chih Lin, Cheng-Chin Wu, Ming-Yii Huang, Wen-Chan Tsai, Chih-Hsing Hung, Po-Lin Kuo
The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926486/novel-epstein-barr-virus-like-particles-incorporating-gh-gl-ebna1-or-gb-lmp2-induce-high-neutralizing-antibody-titers-and-ebv-specific-t-cell-responses-in-immunized-mice
#7
Elizabeth M Perez, Joslyn Foley, Timelia Tison, Rute Silva, Javier Gordon Ogembo
Previous Epstein-Barr virus (EBV) prophylactic vaccines based on the major surface glycoprotein gp350/220 as an immunogen have failed to block viral infection in humans, suggesting a need to target other viral envelope glycoproteins. In this study, we reasoned that incorporating gH/gL or gB, critical glycoproteins for viral fusion and entry, on the surface of a virus-like particle (VLP) would be more immunogenic than gp350/220 for generating effective neutralizing antibodies to prevent viral infection of both epithelial and B cell lines...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925857/analysis-of-the-intestinal-microbial-community-and-inferred-functional-capacities-during-the-host-response-to-pneumocystis-pneumonia
#8
Derrick R Samuelson, Tysheena P Charles, Nicholas M de la Rua, Christopher M Taylor, Eugene E Blanchard, Meng Luo, Judd E Shellito, David A Welsh
BACKGROUND: Pneumocystis pneumonia is a major cause of morbidity and mortality in patients infected with HIV/AIDS. In this study, we evaluated the intestinal microbial communities associated with the development of experimental Pneumocystis pneumonia, as there is growing evidence that the intestinal microbiota is critical for host defense against fungal pathogens. METHODS: C57BL/6 mice were infected with live Pneumocystis murina (P. murina) via intratracheal inoculation and sacrificed 7 and 14 days postinfection for microbiota analysis...
December 7, 2016: Experimental Lung Research
https://www.readbyqxmd.com/read/27925643/primary-and-secondary-hemophagocytic-lymphohistiocytosis-have-different-patterns-of-t-cell-activation-differentiation-and-repertoire
#9
Sandra Ammann, Kai Lehmberg, Udo Zur Stadt, Gritta Janka, Anne Rensing-Ehl, Christian Klemann, Maximilian Heeg, Sebastian Bode, Ilka Fuchs, Stephan Ehl
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome characterized by hyperactivation of lymphocytes and histiocytes. T cells play a key role in HLH pathogenesis, but their differentiation pattern is not well characterized in patients with active HLH. We compared T-cell activation patterns between patients with familial HLH (1°HLH), 2°HLH without apparent infectious trigger (2°HLH) and 2°HLH induced by a viral infection (2°V-HLH). Polyclonal CD8(+) T cells are highly activated in 1°HLH and 2°V-HLH, but less in 2°HLH as assessed by HLA-DR expression and marker combination with CD45RA, CCR7, CD127, PD-1 and CD57...
December 7, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27925349/hepatitis-c-viremia-reversibly-maintains-subset-of-antigen-specific-t-bet-tissue-like-memory-b-cells
#10
Li-Yuan Chang, Yonghai Li, David E Kaplan
BACKGROUND: Chronic antigen exposure and/or aging increases the frequency of T-box expressed in T cells (T-bet)-expressing B-lymphocytes in mice. The frequency and significance of B-cell T-bet expression during chronic hepatitis C (HCV) infection in human subjects has never been described. METHODS: Healthy controls, cirrhotic and non-cirrhotic HCV-infected patients, and non-HCV patients with cirrhosis were recruited. Peripheral blood mononuclear cells were phenotyped for expression of T-bet and related markers by flow cytometry...
December 7, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27925010/the-effects-of-a-simple-method-for-cryopreservation-and-thawing-procedures-on-cord-blood-derived-dc-based-esophageal-carcinoma-vaccine
#11
J Yu, L Xie, S Chen, J Zhang, G Guo, B Chen
BACKGROUND: Producing sufficient numbers of DCs at one time point and subsequently cryopreserving the generated DCs in ready-for-use aliquots for clinical application is useful in cancer treatment. OBJECTIVE: To study the effects of a simplified cryopreservation method and thawing procedures acting on the biological characteristics and specific cytotoxic activity of cord blood derived DC-based esophageal carcinoma vaccine. MATERIALS AND METHODS: CD34+ hematopoietic stem cells were isolated from cord blood using CD34+ Progenitor Cell Isolation Kit by magnetic cell sorting system (MACS)...
July 2016: Cryo Letters
https://www.readbyqxmd.com/read/27924827/pd-1-pd-l-pathway-inhibits-m-tb-specific-cd4-t-cell-functions-and-phagocytosis-of-macrophages-in-active-tuberculosis
#12
Lei Shen, Yan Gao, Yuanyuan Liu, Bingyan Zhang, Qianqian Liu, Jing Wu, Lin Fan, Qinfang Ou, Wenhong Zhang, Lingyun Shao
The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924821/critical-role-of-tslp-responsive-mucosal-dendritic-cells-in-the-induction-of-nasal-antigen-specific-iga-response
#13
S Joo, Y Fukuyama, E J Park, Y Yuki, Y Kurashima, R Ouchida, S F Ziegler, H Kiyono
Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine involved in T helper 2 type immune responses. The primary target of TSLP is myeloid dendritic cells (DCs), however, little is known about the mechanism by which TSLP elicits respiratory IgA immune responses upon mucosal immunization. Here, we found that the levels of TSLP and TSLPR were upregulated in the mucosal DCs of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin (CT) compared with those immunized with PspA alone...
December 7, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27924731/improved-immunogenicity-against-a-her2-neu-derived-peptide-by-employment-of-a-pan-hla-dr-binding-epitope-and-cpg-in-a-balb-c-mice-model
#14
Sahar Tahaghoghi-Hajghorbani, Jalil Tavakkol-Afshari, Mahmoud Reza Jaafari, Haniyeh Ghaffari-Nazari, Elham Masoumi, Seyed Amir Jalali
BACKGROUND: An efficient strategy to improve the immunogenicity of peptide vaccines is the use of a synthetic peptide containing cytotoxic T-lymphocyte (CTL) epitopes with T-helper (Th) inducing-epitopes. OBJECTIVE: Our purpose was to determine the use of human epidermal growth factor receptor-2 (Her2/neu)-specific CTL epitopes plus the pan HLA DR-binding epitope (PADRE) and CpG oligodeoxynucleotides (ODNs) to induce antitumor effects in vaccinated mice. METHOD: Female BALB/c mice were immunized with subcutaneously the different vaccines...
December 6, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27924395/the-effect-of-postoperative-complications-on-survival-of-patients-after-minimally-invasive-esophagectomy-for-esophageal-cancer
#15
Kun-Kun Li, Yin-Jian Wang, Xue-Hai Liu, Qun-You Tan, Yao-Guang Jiang, Wei Guo
BACKGROUND: Minimally invasive esophagectomy (MIE) has been shown to be a feasible technique for the treatment of esophageal cancer; however, its postoperative morbidity remains high. This retrospective study aimed to evaluate the effect of postoperative complications on long-term outcomes in patients who have undergone MIE for esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study enrolled patients who had undergone MIE for ESCC between September 2009 and November 2014; all procedures were performed by a single surgical team...
December 6, 2016: Surgical Endoscopy
https://www.readbyqxmd.com/read/27924074/optimized-t-cell-receptor-mimic-tcrm-chimeric-antigen-receptor-t-cells-directed-towards-the-intracellular-wilms-tumor-1-antigen
#16
S Rafiq, T J Purdon, A F Daniyan, M Koneru, T Dao, C Liu, D A Scheinberg, R J Brentjens
CD19-directed chimeric antigen receptor (CAR) T-cells are clinically effective in a limited set of leukemia patients. However, CAR T-cell therapy thus far has been largely restricted to targeting extracellular tumor-associated antigens (TAA). Herein, we report a T-cell receptor-mimic (TCRm) CAR, termed WT1-28z, that is reactive to a peptide portion of the intracellular onco-protein Wilms Tumor 1(WT1), as it is expressed on the surface of the tumor cell in the context of HLA-A*02:01. T-cells modified to express WT1-28z specifically targeted and lysed HLA-A*02:01+ WT1+ tumors and enhanced survival of mice engrafted with HLA-A*02:01+, WT1+ leukemia or ovarian tumors...
December 7, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27923906/cd4-t-cell-effector-commitment-coupled-to-self-renewal-by-asymmetric-cell-divisions
#17
Simone A Nish, Kyra D Zens, Radomir Kratchmarov, Wen-Hsuan W Lin, William C Adams, Yen-Hua Chen, Bonnie Yen, Nyanza J Rothman, Avinash Bhandoola, Hai-Hui Xue, Donna L Farber, Steven L Reiner
Upon infection, an activated CD4(+) T cell produces terminally differentiated effector cells and renews itself for continued defense. In this study, we show that differentiation and self-renewal arise as opposing outcomes of sibling CD4(+) T cells. After influenza challenge, antigen-specific cells underwent several divisions in draining lymph nodes (LN; DLNs) while maintaining expression of TCF1. After four or five divisions, some cells silenced, whereas some cells maintained TCF1 expression. TCF1-silenced cells were T helper 1-like effectors and concentrated in the lungs...
December 6, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27923824/human-dendritic-cells-mitigate-nk-cell-dysfunction-mediated-by-nonselective-jak%C3%A2-blockade
#18
Shane A Curran, Justin A Shyer, Erin T St Angelo, Lillian R Talbot, Sneh Sharma, David J Chung, Glenn Heller, Katharine C Hsu, Brian C Betts, James W Young
Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-vs-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined...
December 6, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27923697/layer-by-layer-nanoparticle-platform-for-cancer-active-targeting
#19
Min Sung Suh, Jie Shen, Liisa T Kuhn, Diane J Burgess
Nanoparticles as drug delivery carriers have been investigated over the last few decades, particularly for cancer treatment. The rationale in developing such nanoparticles is to maximize drug efficacy while minimizing toxic side effects. This can be most effectively achieved through target specific drug delivery. A novel biocompatible nanoparticle platform prepared using the core-shell self-assembly technique is reported. The core consists of calcium phosphate which is biocompatible and pH-sensitive, and the shell is composed of biocompatible polymers (hyaluronic acid, CD44 targeting moiety; and chitosan, physical cross-linker)...
December 3, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27923677/intact-mitochondrial-ca-2-uniport-is-essential-for-agonist-induced-activation-of-endothelial-nitric-oxide-synthase-enos
#20
Suphachai Charoensin, Emrah Eroglu, Marissa Opelt, Helmut Bischof, Corina T Madreiter-Sokolowski, Andrijana Kirsch, Maria R Depaoli, Saša Frank, Astrid Schrammel, Bernd Mayer, Markus Waldeck-Weiermair, Wolfgang F Graier, Roland Malli
Mitochondrial Ca(2+) uptake regulates diverse endothelial cell functions and has also been related to nitric oxide (NO(•)) production. However, it is not entirely clear if the organelles support or counteract NO(•) biosynthesis by taking up Ca(2+). The objective of this study was to verify whether or not mitochondrial Ca(2+) uptake influences Ca(2+)-triggered NO(•) generation by endothelial NO(•) synthase (eNOS) in an immortalized endothelial cell line (EA.hy926), respective primary human umbilical vein endothelial cells (HUVECs) and eNOS-RFP (red fluorescent protein) expressing human embryonic kidney (HEK293) cells...
December 3, 2016: Free Radical Biology & Medicine
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