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https://www.readbyqxmd.com/read/28914550/socs3-participates-in-cholinergic-pathway-regulation-of-synovitis-in-rheumatoid-arthritis
#1
Tong Li, Shiyao Wu, Sha Li, Xuelian Bai, Hui Luo, Xiaoxia Zuo
Stimulation of the cholinergic inflammatory pathway can promote collagen-induced arthritis (CIA) and inhibit synovitis by Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 signaling. Suppressor of cytokine signaling (SOCS) protein can also regulate inflammatory processes and activate JAK/STAT signal transduction, but its involvement in rheumatoid arthritis (RA) has not been demonstrated. This study investigated the effect of SOCS on cholinergic pathway regulation of synovitis in the fibroblast-like synoviocytes (FLSs) of RA and CIA mice...
September 15, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28911610/myrciaria-cauliflora-extract-improves-diabetic-nephropathy-via-suppression-of-oxidative-stress-and-inflammation-in-streptozotocin-nicotinamide-mice
#2
Jeng-Dong Hsu, Chia-Chun Wu, Chi-Nan Hung, Chau-Jong Wang, Hui-Pei Huang
Myrciaria cauliflora is a functional food rich in anthocyanins, possessing antioxidative and anti-inflammatory properties. Our previous results demonstrated M. cauliflora extract (MCE) had beneficial effects in diabetic nephropathy (DN) and via the inhibition of Ras/PI3K/Akt and kidney fibrosis-related proteins. The purpose of this study was to assess the benefit of MCE in diabetes associated with kidney inflammation and glycemic regulation in streptozotocin-nicotinamide (STZ/NA)-induced diabetic mice. Compared with the untreated diabetic group, MCE significantly improved blood glucose and serum biochemical characteristic levels...
October 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904065/angptl1-interacts-with-integrin-%C3%AE-1%C3%AE-1-to-suppress-hcc-angiogenesis-and-metastasis-by-inhibiting-jak2-stat3-signaling
#3
Qian Yan, Lingxi Jiang, Ming Liu, Dandan Yu, Yu Zhang, Yan Li, Shuo Fang, Yan Li, Ying-Hui Zhu, Yunfei Yuan, Xin Yuan Guan
Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). Here we report that downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivo tumorigenicity, cell motility and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2 mediated anti-apoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28893346/overexpression-of-microrna-34a-5p-inhibits-proliferation-and-promotes-apoptosis-of-human-cervical-cancer-cells-by-downregulation-of-bcl-2
#4
Xiufen Wang, Yucui Xie, Jing Wang
Aberrant expressions of microRNAs (miRNAs) are involved in the development and progression of various types of cancers.In this study, we investigated the roles of miR-34a-5p in proliferation, migration, invasion and apoptosis of cervical cancer cells (HeLa cells). We found that overexpression of miR-34a-5p significantly inhibited the viabilities, migration, and invasion of HeLa cells, but promoted cell apoptosis. Suppression of miR-34a-5p showed opposite effects. The expression levels of Bcl-2 in HeLa cells were increased by miR-34a-5p suppression but decreased by miR-34a-5p overexpression...
August 30, 2017: Oncology Research
https://www.readbyqxmd.com/read/28891251/dose-exposure-response-modeling-to-support-dosing-recommendation-for-phase-3-development-of-baricitinib-in-patients-with-rheumatoid-arthritis
#5
X Zhang, L Chua, C Ernest, W Macias, T Rooney, L S Tham
Baricitinib is an oral inhibitor of Janus kinases (JAK), selective for JAK1 and 2. It demonstrated dose-dependent efficacy in patients with moderate-to-severe rheumatoid arthritis in a Phase 2b study up to 24 weeks. Population pharmacokinetic/pharmacodynamic models were developed to characterize concentration-time profiles and dose/exposure-response relationships for the key efficacy (proportion of patients achieving American College of Rheumatology 20%, 50%, or 70% response rate) and safety endpoints (incidence of anemia) for the Phase 2b study...
September 11, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28890086/sensory-neurons-co-opt-classical-immune-signaling-pathways-to-mediate-chronic-itch
#6
Landon K Oetjen, Madison R Mack, Jing Feng, Timothy M Whelan, Haixia Niu, Changxiong J Guo, Sisi Chen, Anna M Trier, Amy Z Xu, Shivani V Tripathi, Jialie Luo, Xiaofei Gao, Lihua Yang, Samantha L Hamilton, Peter L Wang, Jonathan R Brestoff, M Laurin Council, Richard Brasington, András Schaffer, Frank Brombacher, Chyi-Song Hsieh, Robert W Gereau, Mark J Miller, Zhou-Feng Chen, Hongzhen Hu, Steve Davidson, Qin Liu, Brian S Kim
Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling...
August 26, 2017: Cell
https://www.readbyqxmd.com/read/28887550/identification-of-immunity-related-genes-in-plutella-xylostella-in-response-to-fungal-peptide-destruxin-a-rna-seq-and-dge-analysis
#7
Muhammad Shakeel, Xiaoxia Xu, Jin Xu, Xun Zhu, Shuzhong Li, Xianqiang Zhou, Jialin Yu, Xiaojing Xu, Qiongbo Hu, Xiaoqiang Yu, Fengliang Jin
Plutella xylostella has become the major lepidopteran pest of Brassica owing to its strong ability of resistance development to a wide range of insecticides. Destruxin A, a mycotoxin of entomopathogenic fungus, Metarhizium anisopliae, has broad-spectrum insecticidal effects. However, the interaction mechanism of destruxin A with the immune system of P. xylostella at genomic level is still not well understood. Here, we identified 129 immunity-related genes, including pattern recognition receptors, signal modulators, few members of main immune pathways (Toll, Imd, and JAK/STAT), and immune effectors in P...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28875358/determination-of-critical-quality-attributes-for-a-biotherapeutic-in-the-qbd-paradigm-gcsf-as-a-case-study
#8
Sumit K Singh, Deepak Kumar, Anurag S Rathore
Estimating impact of the various product-related variants and impurities on a biotherapeutic's safety and efficacy is an essential requirement in the quality by design paradigm. In view of the limited role that clinical studies offer in this regard, we demonstrate a preclinical approach to achieve this for granulocyte colony-stimulating factor (GCSF). While our repeated-dose toxicity data suggest that these variants do not elicit any adverse effects or histopathological changes, aggregated GCSF impurity caused sluggishness in animal behavior manifested by a possible muscular injury...
September 5, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28871140/increased-incidence-of-cytomegalovirus-coinfection-in-hcv-infected-patients-with-late-liver-fibrosis-is-associated-with-dysregulation-of-jak-stat-pathway
#9
Marwa K Ibrahim, Ahmed Khedr, Noha G Bader El Din, Ahmed Khairy, Mostafa K El Awady
Herein, we examined the association between cytomegalovirus (CMV) coinfection and the progression of liver fibrosis in hepatitis C virus (HCV) infection, and investigated the effect of CMV coinfection on JAK-STAT pathway. CMV DNAemia was detected by PCR in DNA from controls (n = 120), and HCV patients with early (F0-F1, n = 131) and late (F2-F4, n = 179) liver fibrosis. By quantitative real time PCR (qRT-PCR), we examined the profile of 8 JAK-STAT transcripts in PBMCs RNA from 90 HCV patients (39 CMV positive and 51 CMV negative), 4 CMV mono-infected patients, and 15 controls...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28869471/prevalence-risk-factors-and-complaints-screening-tool-exploration-of-subjective-cognitive-decline-in-a-large-cohort-of-the-chinese-population
#10
Lixiao Hao, Xiaoni Wang, Ling Zhang, Yue Xing, Qihao Guo, Xiaochen Hu, Bin Mu, Yili Chen, Guanqun Chen, Jing Cao, Xiaodong Zhi, Jiaojiao Liu, Xuanyu Li, Liu Yang, Jiachen Li, Wenying Du, Yu Sun, Ting Wang, Zhen Liu, Zheng Liu, Xuexue Zhao, Hongyan Li, Yang Yu, Xue Wang, Jianguo Jia, Ying Han
BACKGROUND: Substantial studies have reported the prevalence and the affecting factors of subjective cognitive decline (SCD). The complaints screening scale has also been used for probing. However, little is known in China. OBJECTIVE: To investigate the prevalence and risk factors of SCD, and explore an SCD complaints screening scale in China. METHODS: Stratified cluster random sampling was conducted. 2,689 residents aged 60-80 years completed questionnaire 1...
September 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28867579/socs2-exacerbates-myocardial-injury-induced-by-ischemia-reperfusion-in-diabetic-mice-and-h9c2-cells-through-inhibiting-the-jak-stat-igf-1-pathway
#11
Mengting Sheng, Zirui Huang, Liming Pan, Min Yu, Cai Yi, Lin Teng, Ling He, Chen Gu, Chunli Xu, Junming Li
AIMS: This study aimed to investigate potential candidates and molecular mechanisms of myocardial ischemia/reperfusion (I/R) injury (MIRI) in type 2 diabetes mellitus. MAIN METHODS: Type 2 diabetic and myocardial I/R mouse models were established with a high fat-diet (HFD) for 24weeks and subjecting to global ischemia/reperfusion for 1h/3h, respectively. Microarray analysis was applied to screen differentially expressed genes (DEGs) in the hearts of these mice. Moreover, H9c2 cells were treated with high glucose (HG) and/or hypoxia and reoxygenation (H/R)...
August 31, 2017: Life Sciences
https://www.readbyqxmd.com/read/28865178/inhibition-of-il-6-jak-stat3-signaling-in-castration-resistant-prostate-cancer-cells-enhances-the-nk-cell-mediated-cytotoxicity-via-alteration-of-pd-l1-nkg2d-ligand-levels
#12
LiJun Xu, XiaoDong Chen, MingJing Shen, Dong-Rong Yang, Laifu Fang, Guobin Weng, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
To investigate whether IL-6 signaling affects the susceptibility of castration resistant prostate cancer (CRPC) cells to cytotoxic action of natural killer (NK) cells, CRPC cell lines (having different IL-6 level) were developed by lentiviral transduction. While observing no secreted IL-6 level in parental C4-2 and CWR22Rv1 cells, we found the IL-6 expression/secretion in these cells was induced after the transduction process and the IL-6 level difference in C4-2siIL-6/sc and CWR22siIL-6/sc cell CRPC cell sets could be detected...
September 2, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28864784/sh003-reverses-drug-resistance-by-blocking-signal-transducer-and-activator-of-transcription-3-stat3-signaling-in-breast-cancer-cells
#13
Hye-Sook Seo, Jin Mo Ku, Hee-Jae Lee, Jong-Kyu Woo, Chunhoo Cheon, Mia Kim, Bo-Hyoung Jang, Yong Cheol Shin, Seong-Gyu Ko
Overcoming drug resistance is an important task for investigators and clinician to achieve successful chemotherapy in cancer patients. Drug resistance is caused by various factors, including the overexpression of P-glycoprotein (P-gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. SH003 is extracted from the mixture of three different herbs, and its anti-cancer effect has been revealed in different cancer cell types. In the present study, we investigated whether SH003 is able to reverse drug resistance using paclitaxel-resistant breast cancer cells (MCF-7/PAC)...
September 1, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28862766/genomic-profiles-of-lung-cancer-associated-with-idiopathic-pulmonary-fibrosis
#14
Ji An Hwang, Deokhoon Kim, Sung-Min Chun, SooHyun Bae, Joon Seon Song, Mi Young Kim, Hyun Jung Koo, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang
Little is known on the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC using targeted exome sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively...
September 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28859930/novel-secolignans-from-peperomia-dindygulensis-and-their-inhibitory-activities-on-jak-stat-signaling-pathways
#15
Ruo-Feng Sun, Chen-Cheng Zhu, Yu Yang, Neng-Jiang Yu
Nineteen secolignans (1-19), including five new ones (1-5), were isolated from the whole plant of Peperomia dindygulensis. Their structures including stereochemistry were determined by spectroscopic methods, in particular NMR and electronic CD (ECD) analysis. All the isolates were evaluated for their inhibitory activities against IFN-γ/STAT1 as well as IL-6/STAT3 signaling pathway by the method of Luciferase assay. Six 2-methene type secolignans (1, 2, 6-9) exhibited significant inhibitory activities against JAK-STAT pathways with the IC50 values both lower than 10μM...
August 30, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28855209/therapeutic-targeting-of-oncogenic-tyrosine-phosphatases
#16
Rochelle Frankson, Zhi-Hong Yu, Yunpeng Bai, Qinglin Li, Ruo-Yu Zhang, Zhong-Yin Zhang
Protein tyrosine phosphatases (PTPs) are exciting and novel targets for cancer drug discovery that work in concert with protein tyrosine kinases (PTKs) in controlling cellular homeostasis. Given the activating role that some PTKs play in initiating growth factor-mediated cellular processes, PTPs are usually perceived as the negative regulators of these events and therefore tumor suppressive in nature. However, mounting evidence indicate that PTPs do not always antagonize the activity of PTKs in regulating tyrosine phosphorylation, but can also play dominant roles in the initiation and progression of signaling cascades that regulate cell functions...
August 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28854975/ruxolitinib-nilotinib-cotreatment-inhibits-leukemia-propagating-cells-in-philadelphia-chromosome-positive-all
#17
Yuan Kong, Yi-Lin Wu, Yang Song, Min-Min Shi, Xie-Na Cao, Hong-Yan Zhao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang
BACKGROUND: As one of the major treatment obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL), relapse of Ph(+)ALL may result from the persistence of leukemia-propagating cells (LPCs). Research using a xenograft mouse assay recently determined that LPCs were enriched in the CD34(+)CD38(-)CD58(-) fraction in human Ph(+)ALL. Additionally, a cohort study demonstrated that Ph(+)ALL patients with a LPCs phenotype at diagnosis exhibited a significantly higher cumulative incidence of relapse than those with the other cell phenotypes even with uniform front-line imatinib-based therapy pre- and post-allotransplant, thus highlighting the need for novel LPCs-based therapeutic strategies...
August 30, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28846158/different-expression-patterns-of-plasma-th1-th2-th17-and-th22-related-cytokines-correlate-with-serum-autoreactivity-and-allergen-sensitivity-in-chronic-spontaneous-urticaria
#18
Qiquan Chen, Hua Zhong, WenChieh Chen, Zhifang Zhai, Zhou Zhou, Zhiqiang Song, Fei Hao
BACKGROUND: Clinical features and basophil activation levels correlate with serum autoreactivity and allergen sensitivity in patients with chronic spontaneous urticaria (CSU). OBJECTIVES: To explore the relationship of the expression patterns of plasma T-helper cell (Th) 1, Th2, Th17, and Th22-related cytokines with the serum autoreactivity and the allergen sensitivity in CSU. METHOD: Twenty related cytokines were measured and analysed in 60 CSU patients, 15 acute urticaria patients, 10 patients with atopic dermatitis (AD), and 15 healthy persons, respectively...
August 28, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28845577/the-safety-and-immunogenicity-of-live-zoster-vaccination-in-patients-with-rheumatoid-arthritis-before-starting-tofacitinib-a-randomized-phase-ii-trial
#19
Kevin L Winthrop, Ann G Wouters, Ernest H Choy, Koshika Soma, Jennifer A Hodge, Chudy I Nduaka, Pinaki Biswas, Elie Needle, Sherry Passador, Christopher F Mojcik, William F Rigby
OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster, and vaccination is recommended for patients ages 50 years and older, prior to starting treatment with biologic agents or tofacitinib. Tofacitinib is an oral JAK inhibitor for the treatment of RA. We evaluated its effect on the immune response and safety of live zoster vaccine (LZV). METHODS: In this phase II, 14-week, placebo-controlled trial, patients ages 50 years and older who had active RA and were receiving background methotrexate were given LZV and randomized to receive tofacitinib 5 mg twice daily or placebo 2-3 weeks postvaccination...
August 28, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28842424/gab2-mediates-hepatocellular-carcinogenesis-by-integrating-multiple-signaling-pathways
#20
Jianghong Cheng, Yanhong Zhong, Shuai Chen, Yan Sun, Lantang Huang, Yujia Kang, Baozhen Chen, Gang Chen, Fengli Wang, Yingpu Tian, Wenjie Liu, Gen-Sheng Feng, Zhongxian Lu
Our previous studies have found that Growth factor receptor-bound protein 2-associated binding protein 2 (Gab2)-a docking protein-governs the development of fatty liver disease. Here, we further demonstrate that Gab2 mediates hepatocarcinogenesis. Compared with a faint expression in para-carcinoma tissue, Gab2 was highly expressed in ∼60-70% of human hepatocellular carcinoma (HCC) specimens. Deletion of Gab2 dramatically suppressed diethylnitrosamine-induced HCC in mice. The oncogenic effects of Gab2 in HepG2 cells were promoted by Gab2 overexpression but were rescued by Gab2 knockdown...
August 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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