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https://www.readbyqxmd.com/read/29028770/expression-and-clinical-correlations-of-co-stimulatory-molecules-on-peripheral-t-lymphocyte-subsets-of-early-stage-severe-sepsis-a-prospective-observational-study
#1
Yi Lu, Le An, Qiang Liu, Chunsheng Li
OBJECTIVE: To investigate the expression and clinical correlations of co-stimulatory molecules on peripheral T cell subsets of severe sepsis (SS) patients. METHODS: Blood samples of patients with community-acquired pneumonia associated SS and healthy controls (HCs) were analyzed. SS patients were followed up for 28 days. Co-stimulatory molecules expression on T cell subsets was determined by flow cytometry analysis. The clinical correlations of these parameters were examined...
October 12, 2017: Shock
https://www.readbyqxmd.com/read/29027915/a-combination-of-immune-checkpoint-inhibition-with-metronomic-chemotherapy-as-a-way-of-targeting-therapy-resistant-cancer-cells
#2
REVIEW
Irina Kareva
Therapeutic resistance remains a major obstacle in treating many cancers, particularly in advanced stages. It is likely that cytotoxic lymphocytes (CTLs) have the potential to eliminate therapy-resistant cancer cells. However, their effectiveness may be limited either by the immunosuppressive tumor microenvironment, or by immune cell death induced by cytotoxic treatments. High-frequency low-dose (also known as metronomic) chemotherapy can help improve the activity of CTLs by providing sufficient stimulation for cytotoxic immune cells without excessive depletion...
October 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29027570/are-we-right-to-consider-mesenchymal-stem-cells-to-be-a-new-perspective-for-patients-with-juvenile-idiopathic-arthritis
#3
REVIEW
Krzysztof Orczyk, Elzbieta Smolewska
Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in childhood. Up to 50% of patients are resistant to standard therapy, which includes non-steroid anti-inflammatory drugs, corticosteroids, disease-modifying anti-rheumatic drugs and biologic therapies. Intra-articular injection of mesenchymal stem cells (MSCs) is proposed as a new approach to JIA treatment. MSCs can modulate inflammation via mechanisms of both adaptive and innate immune response. They are able to inhibit T and B cell proliferation, promote regulatory T cells, suppress the maturation of dendritic cells, stimulate macrophage differentiation into M2 phenotype and reduce effectiveness of natural killer cells...
October 13, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29027229/extracellular-nucleosides-and-nucleotides-as-immunomodulators
#4
REVIEW
Oliver Kepp, Friedemann Loos, Peng Liu, Guido Kroemer
Some anticancer agents induce immunogenic cell death that is accompanied by the emission of danger signals into the tumor microenvironment, thus attracting and activating innate immune effectors and finally inducing anticancer immunity. The release of extracellular nucleosides such as adenosine triphosphate (ATP) from the tumor in response to anticancer therapy plays a pivotal role in the attraction of antigen presenting cells and the activation of inflammasome-mediated proinflammatory cascades. In contrast, the ectonucleotidase-catalyzed phosphohydrolysis of nucleotides to nucleosides reduces the extracellular availability of nucleotides, hence limiting the recruitment and activation of antigen-presenting cells...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29026722/mthfr-3-untranslated-region-polymorphisms-contribute-to-recurrent-pregnancy-loss-risk-and-alterations-in-peripheral-natural-killer-cell-proportions
#5
Eun Sun Kim, Jung Oh Kim, Hui Jeong An, Jung Hyun Sakong, Hyun Ah Lee, Ji Hyang Kim, Eun Hee Ahn, Young Ran Kim, Woo Sik Lee, Nam Keun Kim
OBJECTIVE: To identify the associations between polymorphisms of the 3'-untranslated region (UTR) of methylenetetrahydrofolate reductase (MTHFR) gene, which codes for an important regulatory enzyme primarily involved in folate metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women. METHODS: The study population comprised 369 RPL patients and 228 controls. MTHFR 2572C>A, 4869C>G, 5488C>T, and 6685T>C 3'-UTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis or by TaqMan allelic discrimination assays...
September 2017: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/29026335/challenging-the-standard-of-care-in-advanced-melanoma-focus-on-pembrolizumab
#6
REVIEW
Raghad M Abdul-Karim, C Lance Cowey
The last several years have seen a dramatic rise in the number of effective therapies that have been shown to improve survival outcomes for patients with advanced melanoma. Among these treatments are the immune checkpoint inhibitors, a new class of immunotherapy, that have demonstrated the ability to improve both response rates and survival outcomes. Pembrolizumab, an immune checkpoint inhibitor that blocks the negative regulatory PD-1 receptor on T-cell lymphocytes, has shown improved efficacy compared to standard therapies with an acceptable tolerability profile...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/29025894/nascent-rna-sequencing-reveals-a-dynamic-global-transcriptional-response-at-genes-and-enhancers-to-the-natural-medicinal-compound-celastrol
#7
Noah Dukler, Gregory T Booth, Yi-Fei Huang, Nathaniel Tippens, Colin T Waters, Charles G Danko, John T Lis, Adam Siepel
Most studies of responses to transcriptional stimuli measure changes in cellular mRNA concentrations. By sequencing nascent RNA instead, it is possible to detect changes in transcription in minutes rather than hours and thereby distinguish primary from secondary responses to regulatory signals. Here, we describe the use of PRO-seq to characterize the immediate transcriptional response in human cells to celastrol, a compound derived from traditional Chinese medicine that has potent anti-inflammatory, tumor-inhibitory, and obesity-controlling effects...
October 12, 2017: Genome Research
https://www.readbyqxmd.com/read/29025592/significantly-mutated-genes-and-regulatory-pathways-in-sclc-a-meta-analysis
#8
Varsha Sundaresan, Victor T Lin, Faming Liang, Frederic J Kaye, Reika Kawabata-Iwakawa, Kouya Shiraishi, Takashi Kohno, Jun Yokota, Lei Zhou
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and demands effective targeted therapeutic strategies. In this meta-analysis study, we aim to identify significantly mutated genes and regulatory pathways to help us better understand the progression of SCLC and to identify potential biomarkers. Besides ranking genes based on their mutation frequencies, we sought to identify statistically significant mutations in SCLC with the MutSigCV software. Our analysis identified several genes with relatively low mutation frequency, including PTEN, as highly significant (p < 0...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025424/understanding-immune-phenotypes-in-human-gastric-disease-tissues-by-multiplexed-immunohistochemistry
#9
Le Ying, Feng Yan, Qiaohong Meng, Xiangliang Yuan, Liang Yu, Bryan R G Williams, David W Chan, Liyun Shi, Yugang Tu, Peihua Ni, Xuefeng Wang, Dakang Xu, Yiqun Hu
BACKGROUND: Understanding immune phenotypes and human gastric disease in situ requires an approach that leverages multiplexed immunohistochemistry (mIHC) with multispectral imaging to facilitate precise image analyses. METHODS: We developed a novel 4-color mIHC assay based on tyramide signal amplification that allowed us to reliably interrogate immunologic checkpoints, including programmed death-ligand 1 (PD-L1), cytotoxic T cells (CD8(+)T) and regulatory T cells (Foxp3), in formalin-fixed, paraffin-embedded tissues of various human gastric diseases...
October 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29024803/graft-derived-reconstitution-of-mucosal-associated-invariant-t-cells-after-allogeneic-hematopoietic-cell-transplantation
#10
Abir Bhattacharyya, Laïla-Aïcha Hanafi, Alyssa Sheih, Jonathan L Golob, Sujatha Srinivasan, Michael J Boeckh, Steven A Pergam, Sajid Mahmood, Kelsey K Baker, Ted A Gooley, Filippo Milano, David N Fredricks, Stanley R Riddell, Cameron J Turtle
Mucosal-associated invariant T (MAIT) cells express a semi-invariant Vα7.2(+) T cell receptor (TCR) that recognizes ligands from distinct bacterial and fungal species. In neonates, MAIT cells proliferate coincident with gastrointestinal (GI) bacterial colonization. In contrast, under non-inflammatory conditions adult MAIT cells remain quiescent due to acquired regulation of TCR signaling. Effects of inflammation and the altered GI microbiota after allogeneic hematopoietic cell transplantation (HCT) on MAIT cell reconstitution have not been described...
October 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29024485/placenta-derived-adherent-stromal-cells-improve-diabetes-mellitus-associated-left-ventricular-diastolic-performance
#11
Sophie Van Linthout, Nazha Hamdani, Kapka Miteva, Annika Koschel, Irene Müller, Lena Pinzur, Zami Aberman, Kathleen Pappritz, Wolfgang Albrecht Linke, Carsten Tschöpe
Left ventricular (LV) diastolic dysfunction is among others attributed to cardiomyocyte stiffness. Mesenchymal stromal cells (MSC) have cardiac-protective properties. We explored whether intravenous (i.v.) application of PLacenta-eXpanded (PLX) MSC-like cells (PLX) improves LV diastolic relaxation in streptozotocin (STZ)-induced diabetic mice and investigated underlying mechanisms. Diabetes mellitus was induced by STZ application (50 mg/kg body weight) during five subsequent days. One week after the first STZ injection, PLX or saline were i...
October 10, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29023933/mir-15a-16-1-suppresses-ahr-dependent-il-22-secretion-in-cd4-t-cells-and-contributes-to-immune-mediated-organ-injury
#12
Zhou Lu, Jiajing Liu, Xiaoming Liu, Enyu Huang, Jiao Yang, Jiawen Qian, Dan Zhang, Ronghua Liu, Yiwei Chu
Interleukin-22 (IL-22), as a link between leukocytic and non-leukocytic cells, has gained increasing attention for its pronounced tissue-protective properties. MicroRNAs (miRNAs), emerging as crucial immune modulators, have been reported to be involved in the production and action of various cytokines. However, the precise control of IL-22 by miRNAs and its subsequent actions remained to be elucidated. In this study, we found a negative correlation between the expression of miR-15a/16-1 and IL-22 in the model of concanavalinA (ConA)-induced immune-mediated liver injury...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29023682/short-term-cytokine-stimulation-reveals-regulatory-t-cells-with-down-regulated-foxp3-expression-in-human-peripheral-blood
#13
Paula Tabares, Susanne Berr, Daniela Langenhorst, Birgit Sawitzki, Ineke Ten Berge, Hans-Peter Tony, Thomas Hünig
The identification of regulatory T cells (Treg cells) in human peripheral blood is an important tool in diagnosis, research and therapeutic intervention. As compared to lymphoid tissues, the frequencies of circulating Treg cells identified as CD4(+) CD25(+) Foxp3(+) are, however, low. We here show that many of these cells remain undetected due to transient down regulation of Foxp3, which rapidly decays in the absence of cytokine-mediated STAT5 signals. Short-term incubation of PBMCs or isolated CD4(+) T-cells, but not of lymph node cells, with IL-2, -7, or -15 more than doubles the frequency of Foxp3(+) CD25(+) among CD4(+) T-cells detectable by flow cytometry...
October 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29023598/the-greenland-shark-somniosus-microcephalus-hemoglobins-and-ligand-binding-properties
#14
Roberta Russo, Daniela Giordano, Gianluca Paredi, Francesco Marchesani, Lisa Milazzo, Giovanna Altomonte, Pietro Del Canale, Stefania Abbruzzetti, Paolo Ascenzi, Guido di Prisco, Cristiano Viappiani, Angela Fago, Stefano Bruno, Giulietta Smulevich, Cinzia Verde
A large amount of data is currently available on the adaptive mechanisms of polar bony fish hemoglobins, but structural information on those of cartilaginous species is scarce. This study presents the first characterisation of the hemoglobin system of one of the longest-living vertebrate species (392 ± 120 years), the Arctic shark Somniosus microcephalus. Three major hemoglobins are found in its red blood cells and are made of two copies of the same α globin combined with two copies of three very similar β subunits...
2017: PloS One
https://www.readbyqxmd.com/read/29023469/the-common-oncogenomic-program-of-notch1-and-notch3-signaling-in-t-cell-acute-lymphoblastic-leukemia
#15
Sung Hee Choi, Eric Severson, Warren S Pear, Xiaole S Liu, Jon C Aster, Stephen C Blacklow
Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL), in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells...
2017: PloS One
https://www.readbyqxmd.com/read/29023267/enhanced-th17-responses-in-patients-with-il10-receptor-deficiency-and-infantile-onset-ibd
#16
Dror S Shouval, Liza Konnikova, Alexandra E Griffith, Sarah M Wall, Amlan Biswas, Lael Werner, Moran Nunberg, Jochen Kammermeier, Jeremy A Goettel, Rajsavi Anand, Hannah Chen, Batia Weiss, Jian Li, Anthony Loizides, Baruch Yerushalmi, Tadahiro Yanagi, Rita Beier, Laurie S Conklin, Christen L Ebens, Fernanda G M S Santos, Mary Sherlock, Jeffery D Goldsmith, Daniel Kotlarz, Sarah C Glover, Neil Shah, Athos Bousvaros, Holm H Uhlig, Aleixo M Muise, Christoph Klein, Scott B Snapper
BACKGROUND: IL10 receptor (IL10R) deficiency causes severe infantile-onset inflammatory bowel disease. Intact IL10R-dependent signals have been shown to be important for innate and adaptive immune cell functions in mice. We have previously reported a key role of IL10 in the generation and function of human anti-inflammatory macrophages. Independent of innate immune cell defects, the aim of the current study was to determine the role of IL10R signaling in regulating human CD4 T-cell function...
October 11, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29022387/lactobacillus-plantarum-is-10506-supplementation-reduced-scorad-in-children-with-atopic-dermatitis
#17
C R S Prakoeswa, N Herwanto, R Prameswari, L Astari, S Sawitri, A N Hidayati, D M Indramaya, E R Kusumowidagdo, I S Surono
Lactobacillus plantarum IS-10506 is a novel probiotic isolated from dadih, an Indonesian traditional fermented buffalo milk. It's in vitro and in vivo probiotic properties have been assessed. Probiotic function has been shown in vivo by the suppression of allergic reactions in BALB/c mice through the action of T-regulatory cells cytokines by balancing Th1 and Th2 immune response. Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease characterised by the imbalance of Th1 and Th2. The aim of the study was to assess the probiotic function of L...
October 12, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/29021893/the-efficacy-of-oral-and-subcutaneous-antigen-specific-immunotherapy-in-murine-cow-s-milk-and-peanut-allergy-models
#18
Marlotte M Vonk, Laura Wagenaar, Raymond H H Pieters, Leon M J Knippels, Linette E M Willemsen, Joost J Smit, Betty C A M van Esch, Johan Garssen
BACKGROUND: Antigen-specific immunotherapy (AIT) is a promising therapeutic approach for both cow's milk allergy (CMA) and peanut allergy (PNA), but needs optimization in terms of efficacy and safety. AIM: Compare oral immunotherapy (OIT) and subcutaneous immunotherapy (SCIT) in murine models for CMA and PNA and determine the dose of allergen needed to effectively modify parameters of allergy. METHODS: Female C3H/HeOuJ mice were sensitized intragastrically (i...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/29021795/neuroendocrine-and-immune-responses-undertake-different-fates-following-tryptophan-or-methionine-dietary-treatment-tales-from-a-teleost-model
#19
Rita Azeredo, Marina Machado, António Afonso, Camino Fierro-Castro, Felipe E Reyes-López, Lluis Tort, Manuel Gesto, Marta Conde-Sieira, Jesús M Míguez, José L Soengas, Eva Kreuz, Sven Wuertz, Helena Peres, Aires Oliva-Teles, Benjamin Costas
Methionine and tryptophan appear to be fundamental in specific cellular pathways involved in the immune response mechanisms, including stimulation of T-regulatory cells by tryptophan metabolites or pro-inflammatory effects upon methionine supplementation. Thus, the aim of this study was to evaluate the immunomodulatory effect of these amino acids on the inflammatory and neuroendocrine responses in juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP, respectively, 2× dietary requirement level) or a control diet meeting the amino acids requirement levels (CTRL)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29021521/tristetraprolin-inhibits-macrophage-il-27-induced-activation-of-antitumour-cytotoxic-t-cell-responses
#20
Qinghong Wang, Huan Ning, Hui Peng, Lin Wei, Rong Hou, Daniel F Hoft, Jianguo Liu
IFN-γ-producing cytotoxic T lymphocytes are essential for host defense against viral infection and cancer. Here we show that the RNA-binding tristetraprolin, encoded by Zfp36, is needed for CD8(+) T-cell production of IFN-γ in vivo. When activated in vitro, however, IFN-γ production by naive wild type and tristetraprolin-deficient CD8(+) T-cells is comparable. IL-27 is overproduced by tristetraprolin-deficient macrophages and increased systemically in tristetraprolin-deficient mice. Tristetraprolin suppresses IL-27 production by promoting p28 mRNA degradation...
October 11, 2017: Nature Communications
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