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https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#1
Alexandre Vallée, Rémy Guillevin, Jean-Noël Vallée
The canonical Wnt/β-catenin pathway is up-regulated in gliomas and involved in proliferation, invasion, apoptosis, vasculogenesis and angiogenesis. Nuclear β-catenin accumulation correlates with malignancy. Hypoxia activates hypoxia-inducible factor (HIF)-1α by inhibiting HIF-1α prolyl hydroxylation, which promotes glycolytic energy metabolism, vasculogenesis and angiogenesis, whereas HIF-1α is degraded by the HIF prolyl hydroxylase under normoxic conditions. We focus this review on the links between the activated Wnt/β-catenin pathway and the mechanisms underlying vasculogenesis and angiogenesis through HIF-1α under normoxic conditions in gliomas...
August 19, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28821547/cultivation-in-space-flight-produces-minimal-alterations-in-the-susceptibility-of-bacillus-subtilis-cells-to-72-different-antibiotics-and-growth-inhibiting-compounds
#2
Michael D Morrison, Patricia Fajardo-Cavazos, Wayne L Nicholson
Past results have suggested that bacterial antibiotic susceptibility is altered during space flight. To test this notion, Bacillus subtilis cells were cultivated in matched hardware, medium, and environmental conditions either in spaceflight microgravity on the International Space Station, termed Flight (FL) samples, or at Earth-normal gravity, termed Ground Control (GC) samples. Susceptibility of FL and GC samples was compared to 72 antibiotics and growth-inhibitory compounds using the Omnilog Phenotype Microarray (PM) system...
August 18, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28819022/%C3%AE-adrenergic-signaling-in-mice-housed-at-standard-temperatures-suppresses-an-effector-phenotype-in-cd8-t-cells-and-undermines-checkpoint-inhibitor-therapy
#3
Mark J Bucsek, Guanxi Qiao, Cameron R MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M Kokolus, Jason W-L Eng, Michelle N Messmer, Kristopher Attwood, Scott I Abrams, Bonnie L Hylander, Elizabeth A Repasky
The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8(+) T cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies - physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-adrenergic receptor knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28817954/dissecting-amyloid-beta-deposition-using-distinct-strains-of-the-neurotropic-parasite-toxoplasma-gondii-as-a-novel-tool
#4
Carla M Cabral, Kathryn E McGovern, Wes R MacDonald, Jenna Franco, Anita A Koshy
Genetic and pathologic data suggest that amyloid beta (Aβ), produced by processing of the amyloid precursor protein, is a major initiator of Alzheimer's disease (AD). To gain new insights into Aβ modulation, we sought to harness the power of the coevolution between the neurotropic parasite Toxoplasma gondii and the mammalian brain. Two prior studies attributed Toxoplasma-associated protection against Aβ to increases in anti-inflammatory cytokines (TGF-β and IL-10) and infiltrating phagocytic monocytes. These studies only used one Toxoplasma strain making it difficult to determine if the noted changes were associated with Aβ protection or simply infection...
July 2017: ASN Neuro
https://www.readbyqxmd.com/read/28817109/dysfunctional-natural-killer-cells-in-the-aftermath-of-cancer-surgery
#5
REVIEW
Leonard Angka, Sarwat T Khan, Marisa K Kilgour, Rebecca Xu, Michael A Kennedy, Rebecca C Auer
The physiological changes that occur immediately following cancer surgeries initiate a chain of events that ultimately result in a short pro-, followed by a prolonged anti-, inflammatory period. Natural Killer (NK) cells are severely affected during this period in the recovering cancer patient. NK cells play a crucial role in anti-tumour immunity because of their innate ability to differentiate between malignant versus normal cells. Therefore, an opportunity arises in the aftermath of cancer surgery for residual cancer cells, including distant metastases, to gain a foothold in the absence of NK cell surveillance...
August 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28815581/th1-polarizing-%C3%AE-%C3%AE-t-cells-and-scavenger-receptors-contribute-to-the-pathogenesis-of-pemphigus-vulgaris
#6
Dayasagar Das, Vivek Anand, Sujay Khandpur, V K Sharma, Alpana Sharma
Gamma delta T cells (γδ T cells) and Scavenger receptors are key innate immune machinery playing significant role in regulating immune homeostasis at epithelial surface. The roles of these immune components are not yet characterized for the autoimmune skin disorder Pemphigus Vulgaris (PV). Phenotyping and frequency of γδ T cells estimated by Flowcytometry has shown increased frequency of γδ T cells (6.7% vs. 4.4%) producing IFN-γ (35.2% vs. 26.68%), in circulation of patients compared to controls. Dual cytokine (IFN-γ & IL-4) secreting γδ T cells indicate plasticity of these cells...
August 16, 2017: Immunology
https://www.readbyqxmd.com/read/28815044/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#7
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28813410/identification-of-cmtm6-and-cmtm4-as-pd-l1-protein-regulators
#8
Riccardo Mezzadra, Chong Sun, Lucas T Jae, Raquel Gomez-Eerland, Evert de Vries, Wei Wu, Meike E W Logtenberg, Maarten Slagter, Elisa A Rozeman, Ingrid Hofland, Annegien Broeks, Hugo M Horlings, Lodewyk F A Wessels, Christian U Blank, Yanling Xiao, Albert J R Heck, Jannie Borst, Thijn R Brummelkamp, Ton N M Schumacher
The clinical benefit for patients with diverse types of metastatic cancers that has been observed upon blockade of the interaction between PD-1 and PD-L1 has highlighted the importance of this inhibitory axis in the suppression of tumour-specific T-cell responses. Notwithstanding the key role of PD-L1 expression by cells within the tumour micro-environment, our understanding of the regulation of the PD-L1 protein is limited. Here we identify, using a haploid genetic screen, CMTM6, a type-3 transmembrane protein of previously unknown function, as a regulator of the PD-L1 protein...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#9
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28811963/characterization-of-the-cryoablation-induced-immune-response-in-kidney-cancer-patients
#10
Taigo Kato, Tomoyuki Iwasaki, Motohide Uemura, Akira Nagahara, Hiroki Higashihara, Keigo Osuga, Yuji Ikeda, Kazuma Kiyotani, Jae-Hyun Park, Norio Nonomura, Yusuke Nakamura
Cryoablation is one of treatment modalities for kidney cancer and is expected to induce strong local immune responses as well as systemic T-cell-mediated immune reactions that may lead to the regression of distant metastatic lesions. Thus, the characterization of T cell repertoire and immune environment in tumors before and after treatment should contribute to the better understanding of the cryoablation-induced anticancer immune responses. In this study, we collected tumor tissues from 22 kidney cancer patients, before cryoablation and at 3 mo after cryoablation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811197/seasonal-changes-in-plasma-testosterone-and-cortisol-suggest-an-androgen-mediated-regulation-of-the-pituitary-adrenal-axis-in-the-tarabul-s-gerbil-gerbillus-tarabuli-thomas-1902
#11
Yamina Zatra, Naouel Aknoun-Sail, Arezki Kheddache, Abdelouafi Benmouloud, Salima Charallah, Elara N Moudilou, Jean-Marie Exbrayat, Farida Khammar, Zaina Amirat
In the desert gerbil Gerbillus tarabuli (Thomas, 1902), cortisol is the main glucocorticosteroid produced by the adrenal glands. Plasma cortisol concentrations show highest values when testosterone is reduced and lowest values during the breeding season which occurs from early winter to late spring. In order to specify the implication of testicular androgens in these corticosteroid seasonal variations we investigated the effects induced by gonadectomy performed during the breeding season on the pituitary adrenal axis...
August 12, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28810662/galectin-9-binds-to-o-glycans-on-protein-disulfide-isomerase
#12
Katrin Schaefer, Nicholas E Webb, Mabel Pang, Jenny E Hernandez-Davies, Katharine P Lee, Pascual Gonzalez, Martin V Douglass, Benhur Lee, Linda G Baum
Changes in the T cell surface redox environment regulate critical cell functions, such as cell migration, viral entry and cytokine production. Cell surface protein disulfide isomerase (PDI) contributes to the regulation of T cell surface redox status. Cell surface PDI can be released into the extracellular milieu or can be internalized by T cells. We have found that galectin-9, a soluble lectin expressed by T cells, endothelial cells and dendritic cells, binds to and retains PDI on the cell surface. While endogenous galectin-9 is not required for basal cell surface PDI expression, exogenous galectin-9 mediated retention of cell surface PDI shifted the disulfide/thiol equilibrium on the T cell surface...
September 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28810516/lectin-from-inflorescences-of-ornamental-crop-alpinia-purpurata-acts-on-immune-cells-to-promote-th1-and-th17-responses-nitric-oxide-release-and-lymphocyte-activation
#13
Jéssica de Santana Brito, Gustavo Ramos Salles Ferreira, Emeline Klimczak, Liliya Gryshuk, Nataly Diniz de Lima Santos, Leydianne Leite de Siqueira Patriota, Leyllane Rafael Moreira, Ana Karine Araújo Soares, Bruno Rafael Barboza, Patrícia Maria Guedes Paiva, Daniela Maria do Amaral Ferraz Navarro, Virgínia Maria Barros de Lorena, Cristiane Moutinho Lagos de Melo, Marília Cavalcanti Coriolano, Thiago Henrique Napoleão
Alpinia purpurata is an ornamental crop known as a source of bioactive molecules. This is the first study to report isolation of a lectin (carbohydrate-binding protein) from A. purpurata inflorescences (ApuL). The immunomodulatory potential of ApuL was evaluated by investigating its effects on the production of cytokines and release of nitric oxide by human peripheral blood mononuclear cells (PBMCs). In addition, the differentiation and activation of lymphocytes treated with ApuL was evaluated by immunophenotyping assays...
August 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28808261/atomic-force-microscopy-micro-rheology-reveals-large-structural-inhomogeneities-in-single-cell-nuclei
#14
Michael Lherbette, Ália Dos Santos, Yukti Hari-Gupta, Natalia Fili, Christopher P Toseland, Iwan A T Schaap
During growth, differentiation and migration of cells, the nucleus changes size and shape, while encountering forces generated by the cell itself and its environment. Although there is increasing evidence that such mechanical signals are employed to control gene expression, it remains unclear how mechanical forces are transduced through the nucleus. To this end, we have measured the compliance of nuclei by applying oscillatory strains between 1 and 700 Hz to individual nuclei of multiple mammalian cell-lines that were compressed between two plates...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808010/voltage-gated-calcium-flux-mediates-escherichia-coli-mechanosensation
#15
Giancarlo N Bruni, R Andrew Weekley, Benjamin J T Dodd, Joel M Kralj
Electrically excitable cells harness voltage-coupled calcium influx to transmit intracellular signals, typically studied in neurons and cardiomyocytes. Despite intense study in higher organisms, investigations of voltage and calcium signaling in bacteria have lagged due to their small size and a lack of sensitive tools. Only recently were bacteria shown to modulate their membrane potential on the timescale of seconds, and little is known about the downstream effects from this modulation. In this paper, we report on the effects of electrophysiology in individual bacteria...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807997/phosphoantigen-induced-conformational-change-of-butyrophilin-3a1-btn3a1-and-its-implication-on-v%C3%AE-9v%C3%AE-2-t-cell-activation
#16
Siyi Gu, Joseph R Sachleben, Christopher T Boughter, Wioletta I Nawrocka, Marta T Borowska, Jeffrey T Tarrasch, Georgios Skiniotis, Benoît Roux, Erin J Adams
Human Vγ9Vδ2 T cells respond to microbial infections as well as certain types of tumors. The key initiators of Vγ9Vδ2 activation are small, pyrophosphate-containing molecules called phosphoantigens (pAgs) that are present in infected cells or accumulate intracellularly in certain tumor cells. Recent studies demonstrate that initiation of the Vγ9Vδ2 T cell response begins with sensing of pAg via the intracellular domain of the butyrophilin 3A1 (BTN3A1) molecule. However, it is unknown how downstream events can ultimately lead to T cell activation...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807056/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#17
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806280/integrated-analysis-of-biopsies-from-inflammatory-bowel-disease-patients-identifies-saa1-as-a-link-between-mucosal-microbes-with-th17-and-th22-cells
#18
Mei San Tang, Rowann Bowcutt, Jacqueline M Leung, Martin J Wolff, Uma M Gundra, David Hudesman, Lisa B Malter, Michael A Poles, Lea Ann Chen, Zhiheng Pei, Antonio G Neto, Wasif M Abidi, Thomas Ullman, Lloyd Mayer, Richard A Bonneau, Ilseung Cho, Pʼng Loke
BACKGROUND: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD. METHODS: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD...
August 9, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28804996/in-vitro-evaluation-of-3d-bioprinted-tri-polymer-network-scaffolds-for-bone-tissue-regeneration
#19
Stephanie T Bendtsen, Mei Wei
In vitro evaluations provide vital information on the ability of tissue engineered scaffolds to support cell life and promote natural physiological behaviors in culture. Such assessments are necessary to conduct before implementation of the scaffolds for tissue healing in vivo. The scaffold extracellular matrix must provide the biochemical and mechanical cues necessary to promote cellular attachment, migration and proliferation before differentiation and new tissue deposition can occur. In this study, an in vitro evaluation was conducted to assess the ability of scaffolds 3D printed with a previously developed alginate-polyvinyl alcohol-hydroxyapatite formulation to promote proliferation of encapsulated MC3T3 cells...
August 14, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28803347/melatonin-mitochondria-and-the-skin
#20
REVIEW
Andrzej T Slominski, Michal A Zmijewski, Igor Semak, Tae-Kang Kim, Zorica Janjetovic, Radomir M Slominski, Jaroslaw W Zmijewski
The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis in response to noxious factors. An important part of the skin response to stress is its ability for melatonin synthesis and subsequent metabolism through the indolic and kynuric pathways. Indeed, melatonin and its metabolites have emerged as indispensable for physiological skin functions and for effective protection of a cutaneous homeostasis from hostile environmental factors...
August 12, 2017: Cellular and Molecular Life Sciences: CMLS
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