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https://www.readbyqxmd.com/read/29345196/surfactant-protein-c-dampens-inflammation-by-decreasing-jak-stat-activation-during-lung-repair
#1
Huiyan Jin, Andrzej K Ciechanowicz, Alanna R Kaplan, Lin Wang, Ping Xia Zhang, Yi-Chien Lu, Rachel E Tobin, Brooke A Tobin, Lauren Cohn, Caroline J Zeiss, Patty J Lee, Emanuela M Bruscia, Diane S Krause
Surfactant Protein C (SPC), a key component of pulmonary surfactant, also plays a role in regulating inflammation. SPC deficiency in patients and mouse models is associated with increased inflammation and delayed repair, but the key drivers of SPC-regulated inflammation in response to injury are largely unknown. This study focuses on a new mechanism of SPC as an anti-inflammatory molecule using SPC-TK/SPC-KO (surfactant protein C-thymidine kinase/surfactant protein C knockout) mice, which represent a novel sterile injury model that mimics clinical acute respiratory distress syndrome (ARDS)...
January 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29343721/%C3%A2-133p53-isoform-promotes-tumour-invasion-and-metastasis-via-interleukin-6-activation-of-jak-stat-and-rhoa-rock-signalling
#2
Hamish Campbell, Nicholas Fleming, Imogen Roth, Sunali Mehta, Anna Wiles, Gail Williams, Claire Vennin, Nikola Arsic, Ashleigh Parkin, Marina Pajic, Fran Munro, Les McNoe, Michael Black, John McCall, Tania L Slatter, Paul Timpson, Roger Reddel, Pierre Roux, Cristin Print, Margaret A Baird, Antony W Braithwaite
∆122p53 mice (a model of ∆133p53 isoform) are tumour-prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed ∆122p53 mice with IL-6 null mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence and metastasis. We also show that ∆122p53 activates RhoA-ROCK signalling leading to tumour cell invasion, which is IL-6-dependent and can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we show that Δ133p53 activates these pathways, resulting in invasive and migratory phenotypes in colorectal cancer cells...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29342461/mechanism-of-periostin-production-in-human-bronchial-smooth-muscle-cells
#3
Kosuke Makita, Yu Mikami, Hirotaka Matsuzaki, Naoya Miyashita, Hideyuki Takeshima, Satoshi Noguchi, Masafumi Horie, Hirokazu Urushiyama, Motoyasu Iikura, Masayuki Hojo, Takahide Nagase, Yasuhiro Yamauchi
BACKGROUND: Asthma is a chronic airway inflammatory disease characterized by airway remodeling, in which the bronchial smooth muscle (BSM) cells play an important role. Periostin, a biomarker that reflects Th2-driven inflammatory diseases such as asthma, may play an important role in the asthmatic airway. Although periostin is mainly produced in airway epithelial cells and fibroblasts after interleukin (IL)-13 stimulation, whether BSM cells produce periostin remains unclear. Therefore, we investigated periostin production in BSM cells and the mechanisms involved...
January 18, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29341224/comparative-rna-seq-transcriptome-analysis-on-silica-induced-pulmonary-inflammation-and-fibrosis-in-mice-silicosis-model
#4
Jiayi Chen, Yuqin Yao, Xiaolan Su, Ying Shi, Xuejiao Song, Linshen Xie, Jia You, Liantian Tian, Luo Yang, Aiping Fang, Jingyuan Xiong
Silicosis is a long-established public health issue in developing countries due to increasingly serious air pollution and poorly implemented occupational safety regulation. Inhalation of silica triggers cytotoxicity, oxidative stress, pulmonary inflammation and eventually silicosis. Current understanding in the pathogenesis and mechanism of silicosis is limited, and no effective cure is clinically available once silicosis is developed. A number of studies were conducted to investigate silica-induced alternate gene expressions in pulmonary cells...
January 16, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29340620/delivery-of-tapasin-modified-ctl-epitope-peptide-via-cytoplasmic-transduction-peptide-induces-ctls-by-jak-stat-signaling-pathway-in-vivo
#5
Shanshan Wu, Xiaohua Chen, Yuyan Tang, Yi Zhang, Dan Li, Jie Chen, Jieling Wang, Zhenghao Tang, Guoqing Zang, Yongsheng Yu
Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) play a vital role in viral control and clearance. Recent studies have elucidated that Tapasin, an endoplasmic reticulum chaperone, is a well-known molecule that appears to be essential in peptide-loading process. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway plays an important role in immune response regulation and cytokines secretion. We have previously verified that fusion protein CTP-HBcAg18-27-Tapasin could facilitate the maturation of bone marrow derived dendritic cells and enhance specific CTLs responses in vitro, which might be associated with the activation of JAK/STAT signaling pathway...
January 11, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29340061/analysis-of-the-mutational-landscape-of-classic-hodgkin-lymphoma-identifies-disease-heterogeneity-and-potential-therapeutic-targets
#6
Elena Mata, Antonio Díaz-López, Ana M Martín-Moreno, Margarita Sánchez-Beato, Ignacio Varela, María J Mestre, Carlos Santonja, Fernando Burgos, Javier Menárguez, Mónica Estévez, Mariano Provencio, Beatriz Sánchez-Espiridión, Eva Díaz, Carlos Montalbán, Miguel A Piris, Juan F García
Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29337196/nicorandil-and-theophylline-can-protect-experimental-rats-against-complete-freund-s-adjuvant-induced-rheumatoid-arthritis-through-modulation-of-jak-stat-rankl-signaling-pathway
#7
Ahmed Gaafar Ahmed Gaafar, Basim Anwar Shehata Messiha, Ahmed Mohamed Labib Abdelkafy
Signaling pathways are interesting fields of study of pathogenesis and treatment trials. We elucidated the possible protective effects of nicorandil (15mg/kg/day) and theophylline (20mg/kg/day) on experimentally-induced RA, focusing on the role of JAK (Janus Kinase) / STAT (Signal Transducer and Activator of Transcription) / RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand) / cytokine signaling pathway. Four sets of experiments were performed. First, effect of test agents on normal animals was evaluated...
January 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29337025/hepatosplenic-t-cell-lymphoma-a-review-of-clinicopathologic-features-pathogenesis-and-prognostic-factors
#8
Mariko Yabe, Roberto N Miranda, L Jeffrey Medeiros
Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of T-cell lymphoma that arises most often in adolescents and young adults. Patients with HSTCL commonly present with B-symptoms and cytopenias which may suggest a diagnosis of acute leukemia initially. Patients present with extranodal disease involving the spleen, liver and bone marrow; lymphadenopathy is usually absent. The lymphoma cells can show a spectrum of cell sizes and are of T-cell lineage, often negative for CD4 and CD8 and positive for T-cell receptor γδ or, less often, αβ...
January 11, 2018: Human Pathology
https://www.readbyqxmd.com/read/29335503/tuning-charge-carrier-transport-and-optical-birefringence-in-liquid-crystalline-thin-films-a-new-design-space-for-organic-light-emitting-diodes
#9
Chang-Min Keum, Shiyi Liu, Akram Al-Shadeedi, Vikash Kaphle, Michiel Koen Callens, Lu Han, Kristiaan Neyts, Hongping Zhao, Malte C Gather, Scott D Bunge, Robert J Twieg, Antal Jakli, Björn Lüssem
Liquid-crystalline organic semiconductors exhibit unique properties that make them highly interesting for organic optoelectronic applications. Their optical and electrical anisotropies and the possibility to control the alignment of the liquid-crystalline semiconductor allow not only to optimize charge carrier transport, but to tune the optical property of organic thin-film devices as well. In this study, the molecular orientation in a liquid-crystalline semiconductor film is tuned by a novel blading process as well as by different annealing protocols...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#10
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330478/interaction-of-suppressor-of-cytokine-signalling-3-with-cavin-1-links-socs3-function-and-cavin-1-stability
#11
Jamie J L Williams, Nasser Alotaiq, William Mullen, Richard Burchmore, Libin Liu, George S Baillie, Fred Schaper, Paul F Pilch, Timothy M Palmer
Effective suppression of JAK-STAT signalling by the inducible inhibitor "suppressor of cytokine signalling 3" (SOCS3) is essential for limiting signalling from cytokine receptors. Here we show that cavin-1, a component of caveolae, is a functionally significant SOCS3-interacting protein. Biochemical and confocal imaging demonstrate that SOCS3 localisation to the plasma membrane requires cavin-1. SOCS3 is also critical for cavin-1 stabilisation, such that deletion of SOCS3 reduces the expression of cavin-1 and caveolin-1 proteins, thereby reducing caveola abundance in endothelial cells...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29328945/astaxanthin-ameliorates-cerulein-induced-acute-pancreatitis-in-mice
#12
Hui Zhang, Wenjuan Yang, Yueyue Li, Liangkai Hu, Ying Dai, Jianqing Chen, Shuqi Xu, Xuanfu Xu, Haiqiong Jiang
BACKGROUND: A various of pharmacological effects of astaxanthin has been confirmed. However, the mechanism underlying protective effect of astaxanthin on acute pancreatitis (AP) induced by cerulein still unclear. The present study is to investigate the mechanism underlying the effect of astaxanthin on autophagy and apoptosis via the JAK/STAT3 pathway. METHODS: Intraperitoneal injection of cerulein at hourly intervals followed by lipopolysaccharide injection were used in Balb/C mice...
January 9, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29328487/combination-of-gemcitabine-and-erlotinib-inhibits-recurrent-pancreatic-cancer-growth-in-mice-via-the-jak-stat-pathway
#13
Liwen Chen, Ding'an Zhou, Zhehao Liu, Xinhao Huang, Qianfan Liu, Yiping Kang, Zili Chen, Yuntao Guo, Haitao Zhu, Chengyi Sun
Compared to single gemcitabine treatment, the combination of gemcitabine and erlotinib has shown effective response in patients with locally advanced or metastatic pancreatic cancer. However, the combination therapy has not proven effective in patients with pancreatic cancer after R0 or R1 resection. In the present study, a nude mice model of orthotopic xenotransplantation after tumor resection was established using pancreatic cancer cell lines, BxPC-3 and PANC‑1. Mice were divided in four groups (each with n=12) and were treated as follows: the control group received a placebo via intraperitoneal injection (i...
January 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29326334/clinical-and-inflammatory-phenotyping-by-breathomics-in-chronic-airway-diseases-irrespective-of-the-diagnostic-label
#14
Rianne de Vries, Yennece W F Dagelet, Pien Spoor, Erik Snoey, Patrick M C Jak, Paul Brinkman, Erica Dijkers, Simon K Bootsma, Fred Elskamp, Frans H C de Jongh, Eric G Haarman, Johannes C C M In 't Veen, Anke-Hilse Maitland-van der Zee, Peter J Sterk
Asthma and chronic obstructive pulmonary disease (COPD) are complex and overlapping diseases that include inflammatory phenotypes. Novel anti-eosinophilic/anti-neutrophilic strategies demand rapid inflammatory phenotyping, which might be accessible from exhaled breath.Our objective was to capture clinical/inflammatory phenotypes in patients with chronic airway disease using an electronic nose (eNose) in a training and validation set.This was a multicentre cross-sectional study in which exhaled breath from asthma and COPD patients (n=435; training n=321 and validation n=114) was analysed using eNose technology...
January 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29322424/expression-and-purification-of-jak1-and-socs1-for-structural-and-biochemical-studies
#15
Nicholas P D Liau, Jeffrey J Babon
Interferon gamma (IFNγ) is a potent inflammatory and immune cytokine. IFNγ signals via the interferon gamma receptor (IFNGR), which is constitutively bound to Janus Kinase (JAK) 1 and JAK2 via its intracellular domain. These two JAK proteins then initiate the inflammatory signaling cascade. The most potent inhibitor of IFNγ signaling is Suppressor of Cytokine Signaling 1 (SOCS1). SOCS1 negatively regulates IFNγ signaling pathway (and other pathways) by directly inhibiting JAKs. Here, we describe a protocol for the recombinant production and purification of the JAK1 kinase domain and its inhibitor SOCS1, for structural and biochemical studies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29322414/dissecting-interleukin-6-classic-and-trans-signaling-in-inflammation-and-cancer
#16
Christoph Garbers, Stefan Rose-John
Interleukin-6 is a cytokine synthesized by many cells in the human body. IL-6 binds to a membrane bound IL-6R, which is only present on hepatocytes, some epithelial cells and some leukocytes. The complex of IL-6 and IL-6R binds to the ubiquitously expressed receptor subunit gp130, which forms a homodimer and thereby initiates intracellular signaling via the JAK/STAT and the MAPK pathways. IL-6R expressing cells can cleave the receptor protein to generate a soluble IL-6R (sIL-6R), which can still bind IL-6 and can associate with gp130 and induce signaling even on cells, which do not express IL-6R...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321719/cancer-chemoprevention-and-therapy-using-chinese-herbal-medicine
#17
REVIEW
Lijing Jiao, Ling Bi, Yan Lu, Qin Wang, Yabin Gong, Jun Shi, Ling Xu
Traditional Chinese medicine (TCM) plays an indispensable role in cancer prevention and treatment. Chinese herbal medicine (CHM) is a key component of TCM and has been practiced for thousands of years. A number of naturally occurring products from Chinese herbs extracts exhibit strong inhibitory properties against carcinogenesis, including CHM single-herb extracts, CHM-derived active components, and CHM formulas (the polyherbal combinations), which regulate JAK/STAT, MAPK, and NF-ҡB pathways. The present review aims to report the cancer-preventive effect of CHM with evidence from cell-line, animal, epidemiological, and clinical experiments...
2018: Biological Procedures Online
https://www.readbyqxmd.com/read/29321238/an-open-label-trial-of-jak-1-2-blockade-in-progressive-ifih1-associated-neuroinflammation
#18
Kavitha Kothur, Sushil Bandodkar, Stephanie Chu, Louise Wienholt, Alexandra Johnson, Peter Barclay, Paul A Brogan, Gillian I Rice, Yanick J Crow, Russell C Dale
No abstract text is available yet for this article.
January 10, 2018: Neurology
https://www.readbyqxmd.com/read/29320511/application-of-a-phenotypic-drug-discovery-strategy-to-identify-biological-and-chemical-starting-points-for-inhibition-of-tslp-production-in-lung-epithelial-cells
#19
Adelina Orellana, Vicente García-González, Rosa López, Sonia Pascual-Guiral, Estrella Lozoya, Julia Díaz, Daniel Casals, Antolín Barrena, Stephane Paris, Miriam Andrés, Victor Segarra, Dolors Vilella, Rajneesh Malhotra, Paul Eastwood, Anna Planagumà, Montserrat Miralpeix, Arsenio Nueda
Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation...
2018: PloS One
https://www.readbyqxmd.com/read/29317823/european-perspective-on-the-management-of-rheumatoid-arthritis-clinical-utility-of-tofacitinib
#20
REVIEW
Paweł Kawalec, Katarzyna Śladowska, Iwona Malinowska-Lipień, Tomasz Brzostek, Maria Kózka
Xeljanz® (tofacitinib) is an oral small-molecule inhibitor that reversibly inhibits Janus-activated kinase (JAK)-dependent cytokine signaling, thus reducing inflammation. As a result of these mechanisms, effects on the immune system such as a moderate decrease in the total lymphocyte count, a dose-dependent decrease in natural killer (NK) cell count, and an increase in B-cell count have been observed. Therefore, tofacitinib provides an innovative approach to modulating the immune and inflammatory responses in patients with rheumatoid arthritis (RA), which is especially important in individuals who do not respond to tumor necrosis factor inhibitors or show a loss of response over time...
2018: Therapeutics and Clinical Risk Management
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