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https://www.readbyqxmd.com/read/28525794/stat6-silencing-induces-hepatocellular-carcinoma-derived-cell-apoptosis-and-growth-inhibition-by-decreasing-the-rankl-expression
#1
Tian Qing, Zhang Yamin, Wang Guijie, Jin Yan, Shen Zhongyang
Signal transducer and activator of transcription-6 (STAT6) is highly expressed in various human cancers and considered a regulator of multiple biological processes in cancers, including cell apoptosis. Evidence has indicated that STAT6 predicts a worse prognosis in hepatocellular carcinoma (HCC) patients. The objective of this study was to investigate the effects and mechanism of STAT6 in human HCC cells. We found that STAT6 silencing significantly inhibited HepG2 and Hep3B cell survival and proliferation. We observed that depletion of STAT6 increased HepG2 and Hep3B cell apoptosis by using a histone DNA ELISA detection kit...
May 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28510715/quantitative-specificity-of-stat1-and-several-variants
#2
Basab Roy, Zheng Zuo, Gary D Stormo
The quantitative specificity of the STAT1 transcription factor was determined by measuring the relative affinity to hundreds of variants of the consensus binding site including variations in the length of the site. The known consensus sequence is observed to have the highest affinity, with all variants decreasing binding affinity considerably. There is very little loss of binding affinity when the CpG within the consensus binding site is methylated. Additionally, the specificity of mutant proteins, with variants of amino acids that interact with the DNA, was determined and nearly all of them are observed to lose specificity across the entire binding site...
May 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28510479/increased-expression-of-p22phox-mediates-airway-hyperresponsiveness-in-an-experimental-model-of-asthma
#3
Chandran Nagaraj, Hans Michael Haitchi, Akos Heinemann, Peter Howarth, Andrea Olschewski, Leigh M Marsh
AIM: Chronic airway diseases such as asthma are associated with increased production of reactive oxygen species (ROS) and oxidative stress. Endogenous NADPH oxidases are a major source of superoxide in lung, but their underlying role in asthma pathology is poorly understood. We sought to characterize the involvement of NADPH oxidase in allergic asthma by studying the role of CYBA (p22phox) in human asthma and murine house dust mite (HDM)-induced allergic airway inflammation. RESULTS: Increased expression and localisation of p22-PHOX was observed in biopsies of asthmatic patients...
May 16, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28498822/interleukin-4-and-interleukin-13-increase-nadph-oxidase-1-related-proliferation-of-human-colon-cancer-cells
#4
Han Liu, Smitha Antony, Krishnendu Roy, Agnes Juhasz, Yongzhong Wu, Jiamo Lu, Jennifer L Meitzler, Guojian Jiang, Eric Polley, James H Doroshow
Human colon cancers express higher levels of NADPH oxidase 1 [NOX1] than adjacent normal epithelium. It has been suggested that reactive oxygen species [ROS] derived from NOX1 contribute to DNA damage and neoplastic transformation in the colon, particularly during chronic inflammatory stress. However, the mechanism(s) underlying increased NOX1 expression in malignant tumors or chronic inflammatory states involving the intestine are poorly characterized. We examined the effects of two pro-inflammatory cytokines, IL-4 and IL-13, on the regulation of NOX1...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28494796/a-malignant-solitary-fibrous-tumour-arising-from-the-first-lumbar-vertebra-and-mimicking-an-osteosarcoma-a-case-report
#5
Naoki Oike, Hiroyuki Kawashima, Akira Ogose, Tetsuo Hotta, Toru Hirano, Takashi Ariizumi, Tetsuro Yamagishi, Hajime Umezu, Shoichi Inagawa, Naoto Endo
BACKGROUND: A solitary fibrous tumour (SFT) is an unusual neoplasm typically found in soft tissues. Although SFTs can arise in the bones, they very rarely arise in the vertebral arch. Here, we describe a case of a SFT that arose in the vertebral arch of the first lumbar (L1) spinal vertebrae and mimicked osteosarcoma. CASE PRESENTATION: A 49-year-old woman presented with a 2-month history of lower back pain and a lumbar region mass. Magnetic resonance imaging demonstrated a heterogeneously enhanced mass in the L1 vertebral arch...
May 11, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28490634/inflammatory-cytokines-down-regulate-the-barrier-protective-prostasin-matriptase-proteolytic-cascade-early-in-experimental-colitis
#6
Marguerite S Buzza, Tierra A Johnson, Gregory D Conway, Erik W Martin, Subhradip Mukhopadhyay, Terez Shea-Donohue, Toni M Antalis
Compromised gastrointestinal barrier function is strongly associated with the progressive and destructive pathologies of the two main forms of IBD, Ulcerative Colitis (UC) and Crohns disease (CD). Matriptase is a membrane-anchored serine protease encoded by Suppression of Tumorigenicity-14 (ST14) gene, which is critical for epithelial barrier development and homeostasis. Matriptase barrier protective activity is linked with the glycosyl-phosphatidyl-inositol (GPI)-anchored serine protease prostasin, which is a co-factor for matriptase zymogen activation...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28484679/rare-solitary-fibrous-tumor-in-the-pediatric-neck-a-case-report-and-review-of-the-literature
#7
G Zachary White, Eric L Cox, Erich J Schwartz, Shant A Korkigian
Solitary fibrous tumors (SFT) are a rare type of mesenchymal-derived tumor not commonly found in the pediatric population, especially in the head and neck. Tumors of this nature are most commonly seen in the adult population and are identified with unique immunohistochemical markers, specifically signal transducer and activator of transcription 6 (STAT6) and hematopoietic progenitor cell antigen (CD34). Including SFTs in the differential diagnosis while working up a mass can be difficult considering their relatively non-descript appearance on imaging and the low yield immunohistochemical staining that must be ordered to confirm diagnosis...
April 6, 2017: Curēus
https://www.readbyqxmd.com/read/28484126/mechanisms-underlying-the-pathogenesis-of-hyper-contractility-of-bronchial-smooth-muscle-in-allergic-asthma
#8
Hiroyasu Sakai, Wataru Suto, Yuki Kai, Yoshihiko Chiba
Airway hyperresponsiveness (AHR) and inflammation are key pathophysiological features of asthma. Enhanced contraction of bronchial smooth muscle (BSM) is one of the causes of the AHR. It is thus important for development of asthma therapy to understand the change in the contractile signaling of airway smooth muscle cells associated with the AHR. In addition to the Ca(2+)-mediated phosphorylation of myosin light chain (MLC), contractile agonists also enhance MLC phosphorylation level, Ca(2+)-independently, by inactivating MLC phosphatase (MLCP), called Ca(2+) sensitization of contraction, in smooth muscle cells including airways...
2017: Journal of Smooth Muscle Research, Nihon Heikatsukin Gakkai Kikanshi
https://www.readbyqxmd.com/read/28477193/transcription-factors-downstream-of-il-4-and-tgf-%C3%AE-signals-analysis-by-quantitative-pcr-western-blot-and-flow-cytometry
#9
Atsushi Sugimoto, Ryoji Kawakami, Norihisa Mikami
IL-9-producing Th9 cell is a novel Th cell subset involved in type II allergic inflammations such as asthma. Th9 cells can be induced from naïve Th cells in the presence of IL-4 and TGF-β. It is also well established that downstream signals of IL-4 and TGF-β, including STAT6, IRF4, Smad, and PU.1, directly mediate IL-9 production in Th9 cells. In this chapter we describe the methods of flow cytometry, qPCR and western blot analysis to determine the expression or activation of these transcription factors downstream of IL-4 and TGF-β...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28476499/selective-stimulation-of-the-jak-stat-signaling-pathway-by-silica-nanoparticles-in-human-endothelial-cells
#10
S Siegrist, H Kettiger, E Fasler-Kan, J Huwyler
Silica nanoparticles (SiNP) are frequently used in pharmaceutical formulations. Intravenously administered, these particles are in close contact with the vascular endothelium. However, preliminary safety assessments of these novel excipients have indicated that SiNP are potentially cytotoxic and can trigger inflammation. In order to elucidate mechanisms of SiNP mediated inflammation, cerebral microvascular endothelial cells and primary umbilical endothelial cells were incubated with SiNP at doses between 10ng/ml and 250μg/ml...
May 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28476239/defective-il-4-signaling-in-t-cells-defines-severe-common-variable-immunodeficiency
#11
Eli Taraldsrud, Børre Fevang, Silje F Jørgensen, Kristine Moltu, Vera Hilden, Kjetil Taskén, Pål Aukrust, June H Myklebust, Johanna Olweus
Common variable immunodeficiency (CVID) is defined by hypogammaglobulinemia and B-cell dysfunction, with significant clinical and immunological heterogeneity. Severe non-infectious complications, such as autoimmunity, granulomatous disease and splenomegaly, constitute a major cause of morbidity in CVID patients. T cells are generally regarded important for development of these clinical features. However, while T-cell abnormalities have been found in CVID patients, functional characteristics of T cells corresponding to well-defined clinical subtypes have not been identified...
May 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28472186/stat2-is-involved-in-the-pathogenesis-of-psoriasis-by-promoting-cxcl11-and-ccl5-production-by-keratinocytes
#12
Claus Johansen, Anne Hald Rittig, Maike Mose, Trine Bertelsen, Isabella Weimar, Jakob Nielsen, Thomas Andersen, Tue Kruse Rasmussen, Bent Deleuran, Lars Iversen
The JAK/STAT signaling pathway is suggested to play an important role in the pathogenesis of psoriasis, and recently JAK/STAT inhibitors have shown promising results in psoriasis treatment. The present study aimed to characterize the role of STAT2 in psoriasis. We demonstrated an increased expression of STAT2 and an increased level of phosphorylated/activated STAT2 in lesional compared with nonlesional psoriatic skin. Gene silencing of STAT2 by siRNA in human keratinocytes revealed that upon IFNα stimulation CXCL11 and CCL5 were the only two cytokines, among 102 analyzed, found to be regulated through a STAT2-dependent mechanism...
2017: PloS One
https://www.readbyqxmd.com/read/28454087/evaluation-of-autoantibody-signatures-in-meningioma-patients-using-human-proteome-arrays
#13
Shabarni Gupta, Shuvolina Mukherjee, Parvez Syed, Narendra Goud Pandala, Saket Choudhary, Vedita Anand Singh, Namrata Singh, Heng Zhu, Sridhar Epari, Santosh B Noronha, Aliasgar Moiyadi, Sanjeeva Srivastava
Meningiomas are one of the most common tumors of the Central nervous system (CNS). This study aims to identify the autoantibody biomarkers in meningiomas using high-density human proteome arrays (~17,000 full-length recombinant human proteins). Screening of sera from 15 unaffected healthy individuals, 10 individuals with meningioma grade I and 5 with meningioma grade II was performed. This comprehensive proteomics based investigation revealed the dysregulation of 489 and 104 proteins in grades I and II of meningioma, respectively, along with the enrichment of several signalling pathways, which might play a crucial role in the manifestation of the disease...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450947/the-inflammatory-cytokine-il-22-promotes-murine-gliomas-via-proliferation
#14
Xiguo Liu, Junjing Yang, Wankai Deng
Interleukin (IL)-22 is newly identified proinflammatory cytokine involved in the T helper (Th)17 and Th22 response. However, the possible role of IL-22 in glioma remains uncertain. The results of the present study demonstrated higher expression levels of IL-22 and the receptor IL-22BP in the brain of GL261 glioma-inoculation mice, suggesting the regulatory role of IL-22 in glioma. Injection of IL-22 increased the severity of glioma in vivo and higher expression levels of IL-6, IL-1β and tumor necrosis factor (TNF)-α were detected in the brain using ELISA following IL-22 injection...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28443896/an-msn-peg-ip-drug-delivery-system-and-il13r%C3%AE-2-as-targeted-therapy-for-glioma
#15
Jinlong Shi, Shiqiang Hou, Jianfei Huang, Shanshan Wang, Wei Huan, Chuanjun Huang, Xiaojiang Liu, Rui Jiang, Wenbo Qian, Jingjing Lu, Xiubing Wang, Wei Shi, Rongqin Huang, Jian Chen
A combination of gene therapy and chemotherapy has recently received interest as a targeted therapy for glioma. A mesoporous silica nanoparticle (MSN)-based vehicle coated with IL13Rα2-targeted peptide (IP) using polyethylene glycol (PEG), MSN-PEG-IP (MPI), was constructed and confirmed as a potential glioma-targeted drug delivery system in vitro. In this work, tissue microarray (TMA) results revealed that IL13Rα2 was over-expressed in human glioma tissues and that high expression of IL13Rα2 in patients was associated with poor survival...
April 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28443588/solitary-fibrous-tumors-of-chest-another-look-with-the-oncologic-perspective
#16
Mert Saynak, Nirmal K Veeramachaneni, Jessica L Hubbs, Dilruba Okumuş, Lawrence B Marks
B Solitary fibrous tumors (SFT) are mesenchymal lesions that arise at a variety of sites, most commonly the pleura. Most patients are asymptomatic at diagnosis, with lesions being detected incidentally. Nevertheless, some patients present due to symptoms from local tumor compression (eg. of the airways and pulmonary parenchyma). Furthermore, radiological methods are not always conclusive in making a diagnosis, and thus, pathological analysis is often required. In the past three decades, immunohistochemical techniques have provided a gold standard in SFT diagnosis...
April 6, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28433199/glycoprotein-non-metastatic-melanoma-protein-b-gpnmb-is-highly-expressed-in-macrophages-of-acute-injured-kidney-and-promotes-m2-macrophages-polarization
#17
Letian Zhou, Hui Zhuo, Huiyu Ouyang, Yexin Liu, Fang Yuan, Lin Sun, Fuyou Liu, Hong Liu
Acute kidney injury (AKI) is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. During AKI process, macrophages, one of the important immune response cells, can polarize into M1 and M2 subtype from M0 subtype. It is well-known that M1 macrophages play a pro inflammatory role while M2 macrophages play an anti-inflammatory role. Glycoprotein non-metastatic melanoma protein b (Gpnmb) is a glycosylated transmembrane protein highly expressed in numerous cells, including osteoblasts, dendritic cells and macrophages...
March 31, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#18
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421819/il-4-induces-the-il17rb-gene-transcription-in-monocytic-cells-with-coordinate-autocrine-il-25-signaling
#19
Nathaniel M Weathington, Shreya S Kanth, Qiaoke Gong, James Londino, Akihiko Hoji, Mauricio Rojas, John Trudeau, Sally Wenzel, Rama K Mallampalli
IL-25 and IL-4 signaling in the setting of infection or allergic responses can drive Type 2 inflammation. IL-25 requires the IL-17 receptor B (IL-17Rb) to mediate signaling through nuclear factor kappa B transcriptional activation. Despite the known coexistence of these two cytokines in the Type 2 inflammatory environment, collaborative signaling between the IL-4 and IL-25 axes is poorly explored. Here we demonstrate IL-4 induction of both IL-25 and IL-17Rb protein in human lung tissue culture, primary alveolar macrophages, and the THP-1 monocytic cell line...
April 19, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28420758/the-foxm1-inhibitor-rcm-1-suppresses-goblet-cell-metaplasia-and-prevents-il-13-and-stat6-signaling-in-allergen-exposed-mice
#20
Lifeng Sun, Xiaomeng Ren, I-Ching Wang, Arun Pradhan, Yufang Zhang, Hannah M Flood, Bo Han, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens...
April 18, 2017: Science Signaling
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