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https://www.readbyqxmd.com/read/28445929/the-kinesin-motor-protein-kif7-is-required-for-t-cell-development-and-normal-mhc-expression-on-thymic-epithelial-cells-tec-in-the-thymus
#1
Ching-In Lau, Alessandro Barbarulo, Anisha Solanki, José Ignacio Saldaña, Tessa Crompton
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445867/the-mir-106a-363xpcl1-mirna-cluster-induces-murine-t-cell-lymphoma-despite-transcriptional-activation-of-the-p27kip1-cell-cycle-inhibitor
#2
Daniel A Kuppers, Thomas M Schmitt, Harry C Hwang, Lavanya Samraj, Bruce E Clurman, Matthew L Fero
The miR-106a~363 cluster encodes 6 miRNAs on the X-chromosome which are abundant in blood cells and overexpressed in a variety of malignancies. The constituent miRNA of miR-106a~363 have functional activities in vitro that are predicted to be both oncogenic and tumor suppressive, yet little is known about their physiological functions in vivo. Mature miR-106a~363 (Mirc2) miRNAs are processed from an intragenic, non-protein encoding gene referred to as Xpcl1 (or Kis2), situated at an X-chromosomal locus frequently targeted by retroviruses in murine lymphomas...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445509/functional-genetic-variants-within-the-sirt2-gene-promoter-in-acute-myocardial-infarction
#3
Wentao Yang, Feng Gao, Pei Zhang, Shuchao Pang, Yinghua Cui, Lixin Liu, Guanghe Wei, Bo Yan
Coronary artery disease (CAD), including acute myocardial infarction (AMI) is the complication of atherosclerosis. Recently, genome-wide association studies have identified a large number of CAD-related genetic variants. However, only 10% of CAD cases could be explained. Low frequent and rare genetic variants have been recently proposed to be main causes for CAD. SIRT2 is a member of sirtuin family, NAD(+)-dependent class III deacetylases. SIRT2 is involved in genomic stability, metabolism, inflammation, oxidative stress and autophagy, as well as in platelet function...
2017: PloS One
https://www.readbyqxmd.com/read/28445497/prostaglandin-e2-produced-following-infection-with-theiler-s-virus-promotes-the-pathogenesis-of-demyelinating-disease
#4
Seung Jae Kim, Young-Hee Jin, Byung S Kim
Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV) activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways, resulting in the production of IL-1β via the activation of caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome. The role of IL-1β in the pathogenesis of TMEV-induced demyelinating disease was previously investigated. However, the signaling effects of prostaglandin E2 (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral determinants and the pathogenesis of demyelinating disease are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28445461/tumour-ischaemia-by-interferon-%C3%AE-resembles-physiological-blood-vessel-regression
#5
Thomas Kammertoens, Christian Friese, Ainhoa Arina, Christian Idel, Dana Briesemeister, Michael Rothe, Andranik Ivanov, Anna Szymborska, Giannino Patone, Severine Kunz, Daniel Sommermeyer, Boris Engels, Matthias Leisegang, Ana Textor, Hans Joerg Fehling, Marcus Fruttiger, Michael Lohoff, Andreas Herrmann, Hua Yu, Ralph Weichselbaum, Wolfgang Uckert, Norbert Hübner, Holger Gerhardt, Dieter Beule, Hans Schreiber, Thomas Blankenstein
The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-γ (IFNγ) is critical in most of the analysed models. Although IFNγ can impede tumour growth by acting directly on cancer cells, it must also act on the tumour stroma for effective rejection of large, established tumours. However, which stroma cells respond to IFNγ and by which mechanism IFNγ contributes to tumour rejection through stromal targeting have remained unknown. Here we use a model of IFNγ induction and an IFNγ-GFP fusion protein in large, vascularized tumours growing in mice that express the IFNγ receptor exclusively in defined cell types...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445052/facile-preparation-of-drug-loaded-tristearin-encapsulated-superparamagnetic-iron-oxide-nanoparticles-using-coaxial-electrospray-processing
#6
Manoochehr Rasekh, Zeeshan Ahmad, Richard Barrie Michael Cross, Javier Hernández Gil, James D E T Wilton-Ely, Philip W Miller
Naturally occurring polymers are promising biocompatible materials that have many applications for emerging therapies, drug delivery systems and diagnostic agents. The handling and processing of such materials still constitutes a major challenge which can limit the full exploitation of their properties. This study explores an ambient environment processing technique: coaxial electrospray (CO-ES) to encapsulate genistein (an isoflavonoid and model drug), superparamagnetic iron oxide nanoparticles (SPIONs, 10-15 nm) and a fluorophore (BODIPY) into a layered (triglyceride tristearin shell) particulate system, with a view to constructing a theranostic agent...
April 26, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28444932/the-association-of-lamb1-polymorphism-and-expression-changes-with-the-risk-of-coal-workers-pneumoconiosis
#7
Xiaoming Ji, Baiqun Wu, Ruhui Han, Jingjin Yang, Esther Ayaaba, Ting Wang, Lei Han, Chunhui Ni
BACKGROUND: Pneumoconiosis is a serious occupational disease worldwide, which is characterized by irreversible and diffuse lung fibrotic lesions. Laminin beta 1(LAMB1) is widely expressed in tissues and it is crucial for both lung morphogenesis and physiological function. In this study, we explored the association between LAMB1 rs4320486 and risk of pneumoconiosis in a Chinese population, as well as its mechanisms. METHODS: In this case-control study, 600 CWP patients and 605 controls were genotyped for the LAMB1 rs4320486 polymorphism using TaqMan methods...
April 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28444814/chronic-antibody-mediated-rejection-in-nonhuman-primate-renal-allografts-validation-of-human-histological-and-molecular-phenotypes
#8
B A Adam, R N Smith, I A Rosales, M Matsunami, B Afzali, T Oura, A B Cosimi, T Kawai, R B Colvin, M Mengel
Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded (FFPE) samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously-described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, CAV1), derived from 10-fold cross-validation ROC curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (AUC=0...
April 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28444612/wbp2nl-pawp-mrna-and-protein-expression-in-sperm-cells-are-not-related-to-semen-parameters-fertilization-rate-or-reproductive-outcome
#9
T Freour, M Barragan, A Ferrer-Vaquer, A Rodríguez, Rita Vassena
PURPOSE: WBP2NL/PAWP, a protein found in the post-acrosomal region of mammalian spermatozoa, has been proposed as a sperm-borne oocyte-activating factor (SOAF) contributing to Ca(2+) release within the oocyte and subsequent fertilization and embryo development. However, its relevance as either a diagnostic or a prognostic marker of fertilization failure has been questioned in the recent literature. We analyzed WBP2NL/PAWP gene and protein expression level and localization in patients without previous intracytoplasmic sperm injection (ICSI) cycles in order to assess its association with both sperm characteristics and ability to fertilize...
March 21, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#10
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28443893/trail-np-hybrids-for-cancer-therapy-a-review
#11
REVIEW
H Belkahla, G Herlem, F Picaud, T Gharbi, M Hémadi, S Ammar, O Micheau
Cancer is a worldwide health problem. It is now considered as a leading cause of morbidity and mortality in developed countries. In the last few decades, considerable progress has been made in anti-cancer therapies, allowing the cure of patients suffering from this disease, or at least helping to prolong their lives. Several cancers, such as those of the lung and pancreas, are still devastating in the absence of therapeutic options. In the early 90s, TRAIL (Tumor Necrosis Factor-related apoptosis-inducing ligand), a cytokine belonging to the TNF superfamily, attracted major interest in oncology owing to its selective anti-tumor properties...
April 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28443693/confounder-factors-masking-a-leydig-cell-ovarian-tumor-in-a-post-menopausal-woman-treated-for-androgen-positive-receptor-breast-cancer
#12
Felipe Scipião Moura, Flávia A Costa-Barbosa, Sydney Correia Leao, Sergio Mancini Nicolau, Claudio E Kater, Patrícia T Monteagudo
Post-menopause hyperandrogenism is a condition that needs careful evaluation. Aromatase inhibitors (AI), which are important in the management of positive estrogen breast cancer, and chronic kidney disease (CKD) can puzzle the evaluation of this condition. A postmenopause female with type-2 diabetes and advanced CKD was attended due to progressive virilization, which has started after the introduction of an AI for breast cancer 5 years earlier. Clinical and radiological investigation has confirmed a pure Leydig cell tumor as source of hyperandrogenism...
April 26, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28443628/intestinal-microbiota-link-lymphopenia-to-murine-autoimmunity-via-pd-1-cxcr5-dim-b-helper-t-cell-induction
#13
Toshiki Eri, Kimito Kawahata, Takeyuki Kanzaki, Mitsuru Imamura, Kazuya Michishita, Lisa Akahira, Ei Bannai, Noritada Yoshikawa, Yasumasa Kimura, Takeshi Satoh, Satoshi Uematsu, Hirotoshi Tanaka, Kazuhiko Yamamoto
T cell lymphopenia results in peripheral homeostatic expansion to maintain the T cell immune system, which is termed lymphopenia-induced proliferation (LIP). LIP is a potential risk for expanding autoreactive clones to become pathogenic in human and murine autoimmune diseases. However, the ontogeny of T cells that induce autoantibody production by autoreactive B cells in LIP remains unclear. Transfer of CD4(+)CD25(-) conventional T (Tc) cells into T-cell-deficient athymic nude mice has been previously reported as a LIP-induced autoimmune model which develops organ-specific autoimmune diseases and systemic antinuclear antibodies (ANAs)...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28443247/evaluation-of-a-new-ifn-%C3%AE-release-assay-for-rapid-diagnosis-of-active-tuberculosis-in-a-high-incidence-setting
#14
Gen Li, Feng Li, Hui-Min Zhao, Han-Li Wen, Hai-Cong Li, Chun-Ling Li, Ping Ji, Peng Xu, Kang Wu, Zhi-Dong Hu, Shui-Hua Lu, Douglas B Lowrie, Jian-Xin Lv, Xiao-Yong Fan
Blood-based interferon-gamma (IFN-γ) release assays (IGRAs) have been proven to be useful in the diagnosis of Mycobacterium tuberculosis (Mtb) infection. However, IGRAs have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. The established T-SPOT. TB assay containing Mtb-specific antigens ESAT-6 and CFP10 are widely used for immunodiagonsis of Mtb infection, but the high cost is one of the restricting factors against its clinical application in the developing countries...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28443098/the-lysine-methyltransferase-g9a-in-immune-cell-differentiation-and-function
#15
REVIEW
Sebastian Scheer, Colby Zaph
G9a (KMT1C, EHMT2) is a lysine methyltransferase (KMT) whose primary function is to di-methylate lysine 9 of histone H3 (H3K9me2). G9a-dependent H3K9me2 is associated with gene silencing and acts primarily through the recruitment of H3K9me2-binding proteins that prevent transcriptional activation. Gene repression via G9a-dependent H3K9me2 is critically required in embryonic stem (ES) cells for the development of cellular lineages by repressing expression of pluripotency factors. In the immune system, lymphoid cells such as T cells and innate lymphoid cells (ILCs) can differentiate from a naïve state into one of several effector lineages that require both activating and repressive mechanisms to maintain the correct gene expression program...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28443096/the-microbiota-and-epigenetic-regulation-of-t-helper-17-regulatory-t-cells-in-search-of-a-balanced-immune-system
#16
REVIEW
Annie Luo, Steven T Leach, Romain Barres, Luke B Hesson, Michael C Grimm, David Simar
Immune cells not only affect tissue homeostasis at the site of inflammation but also exert systemic effects contributing to multiple chronic conditions. Recent evidence clearly supports an altered T helper 17/regulatory T cell (Th17/Treg) balance leading to the development and progression of inflammatory diseases that not only affect the gastrointestinal tract but also have whole-body manifestations, including insulin resistance. Epigenetic mechanisms are amenable to both environmental and circulating factors and contribute to determining the T cell landscape...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28442923/soluble-cytotoxic-t-lymphocyte-antigen-4-a-favorable-predictor-in-malignant-tumors-after-therapy
#17
Qiqi Liu, Pingping Hu, Guodong Deng, Jingxin Zhang, Ning Liang, Jian Xie, Lili Qiao, Hui Luo, Jiandong Zhang
PURPOSE: Soluble cytotoxic T-lymphocyte antigen 4 (sCTLA-4), one of the isoforms of CTLA-4, was discovered to be critical in downregulating the negative signal of CTLA-4 in T-cell responses. Contrary to the classical immunosuppressive effect of CTLA-4, its immunoregulatory function might be complicated. However, the clinical significance of sCTLA-4 to immune regulation and the variation in cancer therapy have not been elucidated. We postulated that the level of sCTLA-4 might affect the outcome of cancer prognosis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442606/the-exit-strategy-an-approach-for-identifying-bacterial-proteins-exported-during-host-infection
#18
E F Perkowski, K E Zulauf, D Weerakoon, J D Hayden, T R Ioerger, D Oreper, S M Gomez, J C Sacchettini, M Braunstein
Exported proteins of bacterial pathogens function both in essential physiological processes and in virulence. Past efforts to identify exported proteins were limited by the use of bacteria growing under laboratory (in vitro) conditions. Thus, exported proteins that are exported only or preferentially in the context of infection may be overlooked. To solve this problem, we developed a genome-wide method, named EXIT (exported in vivotechnology), to identify proteins that are exported by bacteria during infection and applied it to Mycobacterium tuberculosis during murine infection...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28442583/seletalisib-characterization-of-a-novel-potent-and-selective-inhibitor-of-pi3k%C3%AE
#19
Rodger A Allen, Daniel C Brookings, Mark J Powell, Jean Delgado, Lindsay K Shuttleworth, Mark Merriman, Ian J Fahy, Roohi Tewari, John P Silva, Louise J Healy, Gareth C G Davie, Breda Twomey, Rona M Cutler, Apoorva Kotian, Andrea Crosby, Gillian McCluskey, Gillian Watt, Andrew Payne
PI3Ks are key signaling enzymes regulating cellular survival, development and function. Expression of the PI3Kδ isoform is largely restricted to leukocytes and it plays a key role in immune cell development and function. Seletalisib is a novel small molecule inhibitor of PI3Kδ that was evaluated in biochemical assays, cellular assays of adaptive and innate immunity, and an in vivo rat model of inflammation. Our findings show that seletalisib is a potent, ATP-competitive and highly selective PI3Kδ inhibitor able to block AKT phosphorylation following activation of the BCR in a B-cell line...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28442260/synthesis-of-benzoxazole-derivatives-as-interleukin-6-antagonists
#20
Darong Kim, Hee Yeon Won, Eun Sook Hwang, Young-Kook Kim, Hea-Young Park Choo
A growing number of studies have demonstrated that interleukin (IL)-6 plays pathological roles in the development of chronic inflammatory disease and autoimmune disease by activating innate immune cells and by stimulating adaptive inflammatory T cells. So, suppression of IL-6 function may be beneficial for prevention and treatment of chronic inflammatory disease. This study reports that a series of synthetic derivatives of benzoxazole have suppressive effects on IL-6-mediated signaling. Among 16 synthetic derivatives of benzoxazole, the compounds 4, 6, 11, 15, 17, and 19 showed a strong suppressive activity against IL-6-induced phosphorylation of signal transducer and activator of transcription (STAT) 3 by 80-90%...
April 7, 2017: Bioorganic & Medicinal Chemistry
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