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https://www.readbyqxmd.com/read/28432378/advances-in-anti-viral-immune-defence-revealing-the-importance-of-the-ifn-jak-stat-pathway
#1
REVIEW
Nicola Raftery, Nigel J Stevenson
Interferon-alpha (IFN-α) is a potent anti-viral cytokine, critical to the host immune response against viruses. IFN-α is first produced upon viral detection by pathogen recognition receptors. Following its expression, IFN-α embarks upon a complex downstream signalling cascade called the JAK/STAT pathway. This signalling pathway results in the expression of hundreds of effector genes known as interferon stimulated genes (ISGs). These genes are the basis for an elaborate effector mechanism and ultimately, the clearance of viral infection...
April 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28427458/whole-exome-sequencing-identifies-novel-candidate-predisposition-genes-for-familial-polycythemia-vera
#2
Elina A M Hirvonen, Esa Pitkänen, Kari Hemminki, Lauri A Aaltonen, Outi Kilpivaara
BACKGROUND: Polycythemia vera (PV), characterized by massive production of erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe), leading to constitutive activation of JAK-STAT signaling pathway. Familial clustering is also observed occasionally, but high-penetrance predisposition genes to PV have remained unidentified. RESULTS: We studied the predisposition to PV by exome sequencing (three cases) in a Finnish PV family with four patients...
April 20, 2017: Human Genomics
https://www.readbyqxmd.com/read/28427244/whole-genome-expression-analyses-of-type-2-diabetes-in-human-skin-reveal-altered-immune-function-and-burden-of-infection
#3
Chun Wu, Xiaopan Chen, Jing Shu, Chun-Ting Lee
Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426026/generation-of-multipotent-induced-cardiac-progenitor-cells-from-mouse-fibroblasts-and-potency-testing-in-ex-vivo-mouse-embryos
#4
Pratik A Lalit, Adriana M Rodriguez, Karen M Downs, Timothy J Kamp
Here we describe a protocol to generate expandable and multipotent induced cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus differs from cell activation and signaling-directed (CASD) reprogramming to cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas CASD reprogramming can generate various cell types depending on culture conditions and raises the possibility of transitioning through a pluripotent cell state...
May 2017: Nature Protocols
https://www.readbyqxmd.com/read/28425456/salt-suppresses-ifn%C3%AE-inducible-chemokines-through-the-ifn%C3%AE-jak1-stat1-signaling-pathway-in-proximal-tubular-cells
#5
Yohei Arai, Daiei Takahashi, Kenichi Asano, Masato Tanaka, Mayumi Oda, Shigeru B H Ko, Minoru S H Ko, Shintaro Mandai, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
The mechanisms of immunoactivation by salt are now becoming clearer. However, those of immunosuppression remain unknown. Since clinical evidence indicates that salt protects proximal tubules from injury, we investigated mechanisms responsible for salt causing immunosuppression in proximal tubules. We focused on cytokine-related gene expression profiles in kidneys of mice fed a high salt diet using microarray analysis and found that both an interferon gamma (IFNγ) inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor, CXCR3, were suppressed...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424262/magnesium-reduces-hepatic-lipid-accumulation-in-yellow-catfish-pelteobagrus-fulvidraco-and-modulates-lipogenesis-and-lipolysis-via-ppara-jak-stat-and-ampk-pathways-in-hepatocytes
#6
Chuan-Chuan Wei, Kun Wu, Yan Gao, Li-Han Zhang, Dan-Dan Li, Zhi Luo
Background: Magnesium influences hepatic lipid deposition in vertebrates, but the underlying mechanism is unknown.Objective: We used yellow catfish and their isolated hepatocytes to test the hypothesis that magnesium influences lipid deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow catfish (mean ± SEM weight: 3.43 ± 0.02 g, 3 mo old, mixed sex) were fed a 0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C)...
April 19, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28424246/enteropathy-associated-t-cell-lymphoma-subtypes-are-characterized-by-loss-of-function-of-setd2
#7
Andrea B Moffitt, Sarah L Ondrejka, Matthew McKinney, Rachel E Rempel, John R Goodlad, Chun Huat Teh, Sirpa Leppa, Susanna Mannisto, Panu E Kovanen, Eric Tse, Rex K H Au-Yeung, Yok-Lam Kwong, Gopesh Srivastava, Javeed Iqbal, Jiayu Yu, Kikkeri Naresh, Diego Villa, Randy D Gascoyne, Jonathan Said, Magdalena B Czader, Amy Chadburn, Kristy L Richards, Deepthi Rajagopalan, Nicholas S Davis, Eileen C Smith, Brooke C Palus, Tiffany J Tzeng, Jane A Healy, Patricia L Lugar, Jyotishka Datta, Cassandra Love, Shawn Levy, David B Dunson, Yuan Zhuang, Eric D Hsi, Sandeep S Dave
Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis...
April 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28424232/spatiotemporal-regulation-of-cell-fusion-by-jnk-and-jak-stat-signaling-during-drosophila-wound-healing
#8
Ji-Hyun Lee, Chan-Wool Lee, Si-Hyoung Park, Kwang-Min Choe
Cell-cell fusion is widely observed during development and disease and imposes a dramatic change on participating cells. Cell fusion should be tightly controlled, but the underlying mechanism is poorly understood. Here, we found that the JAK/STAT pathway suppressed cell fusion during wound healing and delimited the event to the vicinity of the wound in the Drosophila larval epidermis. In the absence of JAK/STAT signaling, a large syncytium containing 3-fold the number of nuclei observed in wild-type tissue formed in wounded epidermis...
April 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#9
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signaling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418923/osu-a9-inhibits-pancreatic-cancer-cell-lines-by-modulating-p38-jak-stat3-signaling
#10
Wan-Chi Tsai, Li-Yuan Bai, Yi-Jin Chen, Po-Chen Chu, Ya-Wen Hsu, Aaron M Sargeant, Jing-Ru Weng
Pancreatic cancer is an aggressive malignancy that is the fourth leading cause of death worldwide. Since there is a dire need for novel and effective therapies to improve the poor survival rates of advanced pancreatic cancer patients, we analyzed the antitumor effects of OSU-A9, an indole-3-carbinol derivative, on pancreatic cancer cell lines in vitro and in vivo. OSU-A9 exhibited a stronger antitumor effect than gemcitabine on two pancreatic cancer cell lines, including gemcitabine-resistant PANC-1 cells. OSU-A9 treatment induced apoptosis, the down-regulation of Akt phosphorylation, up-regulation of p38 phosphorylation and decreased phosphorylation of JAK and STAT3...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415825/recombinant-human-erythropoietin-stimulates-melanoma-tumor-growth-through-activation-of-initiation-factor-eif4e
#11
Annabelle Julius, Anjali Desai, Raymond L Yung
Recombinant human erythropoietin (EPO) is standard treatment for anemia in cancer patients. Recent clinical trials suggest that EPO may accelerate tumor progression and increase mortality. However, the evidence supporting a growth-promoting effect of EPO has remained controversial. Employing an in vivo model of B16 murine melanoma, we observed that administration of EPO to tumor bearing C57BL/6 mice resulted in pronounced acceleration of melanoma growth. Our in vitro studies demonstrate that B16 murine melanoma cells express EPOR, both at the protein and mRNA levels...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415722/stat3-phosphorylation-is-required-for-embryonic-stem-cells-ground-state-maintenance-in-2i-culture-media
#12
Dan Wang, Hui Sang, Kaiyue Zhang, Yan Nie, Shuang Zhao, Yan Zhang, Ningning He, Yuebing Wang, Yang Xu, Xiaoyan Xie, Zongjin Li, Na Liu
Embryonic stem cells (ES cells) can be maintained its undifferentiated state with feeder cells or LIF, which can activate Jak/Stat3 pathway. Recently, it has been reported a new culture condition comprising serum-free medium with ERK and GSK3β inhibitors (2i) could drive ES cells into a state of pluripotency more like inner cell mass (ICM) in mouse blastocysts called ground state. However, although 2i could sustain ES cells self-renewal, LIF is routinely added. The roles of Stat3 activation are still unclear now...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415697/down-regulation-of-interleukin-7-receptor-il-7r-contributes-to-central-nervous-system-demyelination
#13
Xudan Lei, Shijiao Cai, Yang Chen, Jianlin Cui, Yajie Wang, Zongjin Li, Yuhao Li
Interleukin 7 receptor (IL-7R) has been associated with the pathogenesis of multiple sclerosis (MS), though the mechanisms are not clear. Because myelin expression is highly conserved between zebrafish and mammals, zebrafish have become an ideal model for studying demyelination. We used a transgenic (Tg; mbp:nfsB-egfp) zebrafish line in which oligodendrocytes expressed green fluorescent protein (GFP) from the larval stage to adulthood. Exposing adult transgenic zebrafish to metronidazole induced demyelination that resembled the morphological changes associated with the early stages of MS...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415601/regulatory-network-of-gata3-in-pediatric-acute-lymphoblastic-leukemia
#14
Qianqian Hou, Fei Liao, Shouyue Zhang, Duyu Zhang, Yan Zhang, Xueyan Zhou, Xuyang Xia, Yuanxin Ye, Hanshuo Yang, Zhaozhi Li, Leiming Wang, Xi Wang, Zhigui Ma, Yiping Zhu, Liang Ouyang, Yuelan Wang, Hui Zhang, Li Yang, Heng Xu, Yang Shu
GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415594/interaction-of-epstein-barr-virus-genes-with-human-gastric-carcinoma-transcriptome
#15
Ruiyuan Zhang, Michael J Strong, Melody Baddoo, Zhen Lin, Yu-Ping Wang, Erik K Flemington, Yao-Zhong Liu
Gastric carcinoma (GC) is a leading cause of mortality. 10% of GC cases are related with EBV (Epstein-Barr virus) infection. The detailed mechanistic roles EBV genes play and especially the interaction between the viral genes and human genes in GC remain unclear. In this study, raw fastq data from 285 GC samples were downloaded from TCGA (The Cancer Genome Atlas), including 25 EBV positive (EBV+) GC samples and 260 EBV negative (EBV-) GC samples. RNA-seq based expression data were generated for both human genes (among all the samples) and for the EBV genes (among the 25 EBV+ samples)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413750/an-optically-isotropic-antiferroelectric-liquid-crystal-oi-aflc-display-mode-operating-over-a-wide-temperature-range-using-ternary-bent-core-liquid-crystal-mixtures
#16
Leah Bergquist, Cuiyu Zhang, Roberta R Ribeiro de Almeida, Brittany Pellegrene, Miroslaw Salamonczyk, Matthew Kim, Jung-Im Hwang, Kyeong-Jin Kim, Joun-Ho Lee, Antal Jákli, Torsten Hegmann
We report on the synthesis and characterization of bent-core liquid crystal (LC) compounds and the preparation of mixtures that provide an optically isotropic antiferroelectric (OI-AFLC) liquid crystal display mode over a very wide temperature interval and well below room temperature. From the collection of compounds synthesized during this study, we recognized that several ternary mixtures displayed a modulated SmCaPA phase down to below -40 °C and up to about 100 °C on both heating and cooling, as well as optical tilt angles in the transformed state of approximately 45° (optically isotropic state)...
April 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28413047/a-homolog-of-teleostean-signal-transducer-and-activator-of-transcription-3-stat3-from-rock-bream-oplegnathus-fasciatus-structural-insights-transcriptional-modulation-and-subcellular-localization
#17
S D N K Bathige, William Shanthakumar Thulasitha, Navaneethaiyer Umasuthan, J D H E Jayasinghe, Qiang Wan, Bo-Hye Nam, Jehee Lee
Signal transducer and activator of transcription 3 (STAT3) is one of the crucial transcription factors in the Janus kinase (JAK)/STAT signaling pathway, and it was previously considered as acute phase response factor. A number of interleukins (ILs) such as IL-5, IL-6, IL-9, IL-10, IL-12, and IL-22 are known to be involved in activation of STAT3. In addition, various growth factors and pathogenic or oxidative stresses mediate the activation of a wide range of functions via STAT3. In this study, a STAT3 homolog was identified and functionally characterized from rock bream (RbSTAT3), Oplegnathus fasciatus...
April 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28413030/the-role-matrix-metalloproteinases-in-the-production-of-aortic-aneurysm
#18
Simon W Rabkin
Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle cells in the aortic media and the destruction of extracellular matrix (ECM). Furthermore, AAA have evidence of inflammation and the cellular elements involved in inflammation such as macrophages can produce and/or activate MMPs This chapter focuses on human aortic aneurysm that are not due to specific known genetic causes because this type of aneurysm is the more common type...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28411130/ifitm1-suppression-blocks-proliferation-and-invasion-of-aromatase-inhibitor-resistant-breast-cancer-in%C3%A2-vivo-by-jak-stat-mediated-induction-of-p21
#19
Asona J Lui, Eric S Geanes, Joshua Ogony, Fariba Behbod, Jordan Marquess, Kelli Valdez, William Jewell, Ossama Tawfik, Joan Lewis-Wambi
Interferon induced transmembrane protein 1 (IFITM1) belongs to a family of interferon stimulated genes (ISGs) that is associated with tumor progression and DNA damage resistance, however, its role in endocrine resistance is not known. Here, we correlate IFITM1 expression with clinical stage and poor response to endocrine therapy in a tissue microarray consisting of 94 estrogen receptor (ER)-positive breast tumors. IFITM1 overexpression is confirmed in the AI-resistant MCF-7:5C cell line and not found in AI-sensitive MCF-7 cells...
April 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28410601/the-diagnosis-and-management-of-nk-t-cell-lymphomas
#20
REVIEW
Eric Tse, Yok-Lam Kwong
Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignancy of putative NK-cell origin, with a minority deriving from the T-cell lineage. Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most commonly (80%) in the nose and upper aerodigestive tract, less commonly (20%) in non-nasal areas (skin, gastrointestinal tract, testis, salivary gland), and rarely as disseminated disease with a leukemic phase...
April 14, 2017: Journal of Hematology & Oncology
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