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https://www.readbyqxmd.com/read/27911870/mir-146a-polymorphism-correlates-with-lung-cancer-risk-in-chinese-nonsmoking-females
#1
Zhihua Yin, Zhigang Cui, Yangwu Ren, Lingzi Xia, Hang Li, Baosen Zhou
This study provides evidence that the common rs2910164 polymorphism in miR-146a strongly correlates with lung cancer risk in nonsmoking females in northeast China. The genotypes of miR-146a rs2910164 were determined in 1131 patients with lung cancer and 1003 healthy control subjects. Tissue samples were used to evaluate the association between miRNA expression and lung cancer risk as well as the correlation between rs2910164 genotypes and miR-146a expression. The secondary structures of the wild-type and variant miR-146a sequences were predicted, and luciferase-based target assays were used to test whether miR-146a bound to tumor necrosis factor receptor associated factor 6 (TRAF6) mRNA...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911090/antitumor-activity-of-portulaca-oleracea-l-polysaccharide-on-hela-cells-through-inducing-tlr4-nf-%C3%AE%C2%BAb-signaling
#2
Rui Zhao, Tao Zhang, Baoling Ma, Xing Li
Abstarct We have previously shown that Portulaca oleracea L. polysaccharide (POL-P3b) possesses the ability to inhibit cervical cancer cell growth in vitro and in vivo. In this study, we explored how toll-like receptor 4 (TLR4) signaling correlated with the antitumor mechanism of POL-P3b. Western blotting was utilized to detect the expression of TLR4 and the downstream signaling pathway. The level of inflammatory mediator was quantified using enzyme-linked immunosorbent assay (ELISA) kits. The effects of POL-P3b on the proliferation and apoptosis in HeLa cells were determined by WST-8 assay and Hoechst 33342/propidium iodide (PI) assay...
December 2, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27904767/mir-146a-suppresses-hepatocellular-carcinoma-by-downregulating-traf6
#3
Yong Zu, Yanhong Yang, Jiyun Zhu, Xiaobo Bo, Shuangxing Hou, Bo Zhang, Jiangfeng Qiu, Jing Zheng
MicroRNAs have been proven to play important roles in many biological processes such as cellular growth and differentiation, apoptosis, and modulation of host response to viral infection. In the present study, we find that the expression of miR-146a was decreased in hepatocellular carcinoma (HCC) tissues compared with corresponding adjacent tissues, and the expression level in HCC cell lines was lower than in a normal liver cell. Over-expression suppressed the proliferation and invasion of HCC cells. In addition, luciferase reporter assays and western blotting confirmed that miR-146a directly target TRAF6 which attenuated the effect of miR-146a on cell proliferation and invasion in HepG2 and SMMC7721 cells...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27898007/limb-remote-ischemic-postconditioning-reduces-ischemia-reperfusion-injury-by-inhibiting-nadph-oxidase-activation-and-myd88-traf6-p38map-kinase-pathway-of-neutrophils
#4
Gangling Chen, Xinyi Ye, Jiangwei Zhang, Tingli Tang, Lin Li, Peirong Lu, Qi Wu, Boyang Yu, Junping Kou
Limb remote ischemic postconditioning (LRIP) has been confirmed to reduce the ischemia-reperfusion injury but its mechanisms are still not clear. This study clarified the mechanism of LRIP based on the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and Myeloid differentiation factor 88 (MyD88)-Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6)-P38 pathway of neutrophils. Rat middle cerebral artery occlusion (MCAO) model was used in this study. Ischemia-reperfusion injury was carried out by MCAO 1...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27896363/oxygen-ultra-fine-bubbles-water-administration-prevents-bone-loss-of-glucocorticoid-induced-osteoporosis-in-mice-by-suppressing-osteoclast-differentiation
#5
T Noguchi, K Ebina, M Hirao, T Morimoto, K Koizumi, K Kitaguchi, H Matsuoka, T Iwahashi, H Yoshikawa
: Oxygen ultra-fine bubbles (OUB) saline injection prevents bone loss of glucocorti\coid-induced osteoporosis in mice, and OUB inhibit osteoclastogenesis via RANK-TRAF6-c-Fos-NFATc1 signaling and RANK-p38 MAPK signaling in vitro. INTRODUCTION: Ultra-fine bubbles (<200 nm in diameter) have several unique properties, and they are tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUB) on glucocorticoid-induced osteoporosis (GIO) model mice...
November 28, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/27890916/polydatin-ameliorates-staphylococcus-aureus-induced-mastitis-in-mice-via-inhibiting-tlr2-mediated-activation-of-the-p38-mapk-nf-%C3%AE%C2%BAb-pathway
#6
Kang-Feng Jiang, Gan Zhao, Gan-Zhen Deng, Hai-Chong Wu, Nan-Nan Yin, Xiu-Ying Chen, Chang-Wei Qiu, Xiu-Li Peng
Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureus-induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation...
November 28, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27890776/epigallocatechin-3-gallate-alleviates-paraquat-induced-acute-lung-injury-and-inhibits-upregulation-of-toll-like-receptors
#7
Haitao Shen, Na Wu, Zhenning Liu, Hongyu Zhao, Min Zhao
AIMS: To evaluate the detoxifying effect of epigallocatechin-3-gallate (EGCG) on paraquat (PQ)-induced acute lung injury in mice, and to explore the action mechanisms. MAIN METHODS: Following administration of PQ, the mice received a low, a medium or a high dose of EGCG daily for three days. Histopathology of the lungs were examined by H&E staining. The levels of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay...
November 24, 2016: Life Sciences
https://www.readbyqxmd.com/read/27889748/mir-146a-regulates-inflammatory-infiltration-by-macrophages-in-polymyositis-dermatomyositis-by-targeting-traf6-and-affecting-il-17-icam-1-pathway
#8
Yuanqin Yin, Fei Li, Jing Shi, Songlin Li, Jingjing Cai, Youhong Jiang
BACKGROUND/AIMS: The primary objective of this study was to investigate the role of miR-146a in inducing the inflammatory infiltration of macrophages in polymyositis/dermatomyositis (PM/DM) through targeting TNF receptor associated factor 6 (TRAF6), which may further down-regulate the Interleukin-17 (IL-17)/Intercellular Adhesion Molecule 1 (ICAM-1) pathway. METHODS: Biopsies were collected from PM/DM patients and healthy volunteers. PM/DM model establishment and macrophage isolation were performed on Sprague Dawley (SD) rats...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27875107/the-effect-of-elevated-intra-abdominal-pressure-on-tlr4-signaling-in-intestinal-mucosa-and-on-intestinal-bacterial-translocation-in-a-rat
#9
Adam Strier, Dragan Kravarusic, Arnold G Coran, Isaac Srugo, Nir Bitterman, Tatiana Dorfman, Yulia Pollak, Ibrahim Matter, Igor Sukhotnik
BACKGROUND: Recent evidence suggests that elevated intra-abdominal pressure (IAP) may adversely affect the intestinal barrier function. Toll-like receptor 4 (TLR-4) is responsible for the recognition of bacterial endotoxin or lipopolysaccharide and for initiation of the Gram-negative septic shock syndrome. The objective of the current study was to determine the effects of elevated IAP on intestinal bacterial translocation (BT) and TLR-4 signaling in intestinal mucosa in a rat model. METHODS: Male Sprague-Dawley rats were randomly assigned to one of two experimental groups: sham animals (Sham) and IAP animals who were subjected to a 15 mmHg pressure pneumoperitoneum for 30 minutes...
November 22, 2016: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/27869166/skp2-loss-destabilizes-ezh2-by-promoting-traf6-mediated-ubiquitination-to-suppress-prostate-cancer
#10
W Lu, S Liu, B Li, Y Xie, M G Izban, B R Ballard, S A Sathyanarayana, S E Adunyah, R J Matusik, Z Chen
EZH2 is crucial for the progression of prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) through upregulation and activation of progenitor genes, as well as androgen receptor (AR)-target genes. However, the mechanisms by which EZH2 is regulated in PCa and CRPC remain elusive. Here we report that EZH2 is post-transcriptionally regulated by SKP2 in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of Skp2, Ezh2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse embryonic fibroblasts (MEFs) and Pten null mouse prostate tissues...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27845876/hypoxia-induced-microrna-146a-represses-bcl-2-through-traf6-irak1-but-not-smad4-to-promote-chondrocyte-autophagy
#11
Guanghui Chen, Xin Gao, Jing Wang, Cheng Yang, Yang Wang, Yonggang Liu, Weiwei Zou, Tielong Liu
It has been showed hypoxia stimulation promotes chondrocytes autophagy partly through HIF-1alpha, miR-146a and Bcl-2 progressively, and this mechanism represented the connection among hypoxia, miR-146a and autophagy, and provides a possible therapeutic strategy for osteoarthritis. However, the interaction between miR-146a and Bcl-2 is still unclear. Here in hypoxia environment, we quantified the three reported miR-146a targets: two inflammation related targets Traf6, IRAK1; and the only reported target in chondrocytes Smad4...
November 15, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27830143/microrna-146a-contributes-to-sci-recovery-via-regulating-traf6-and-irak1-expression
#12
Jinsong Wei, Jiafeng Wang, Yulan Zhou, Shouquan Yan, Keshen Li, Hongsheng Lin
MicroRNA-146a participates in spinal cord injury (SCI) recovery. Until recently, how miRNA-146a participates in SCI remained unclear. In this study, we tried to explore the roles of miRNA-146a in the recovery of SCI using a rat model. The expression of the probable target genes of miRNA-146a (including IRAK1 and TARF6) as well as proinflammation cytokines were measured until 7 days after surgery in the three groups (sham group, SCI group, and miRNA-146a antagomir injection group). Also, the animals' motivations were estimated using Basso Beattie Bresnahan (BBB) during the whole experiment...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27818344/traf6-is-a-critical-factor-in-fish-immune-response-to-virus-infection
#13
Jingguang Wei, Shaoqing Zang, Meng Xu, Qiaojun Zheng, Xiuli Chen, Qiwei Qin
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is one of the key adaptor molecule in Toll-like receptor signal transduction that triggers downstream cascades involved in innate immunity. In our previous study, the molecular characteristics of EtTRAF6 (TRAF6 from Epinephelus tauvina), the tissue distributions, expression patterns after challenging with bacterial and viral pathogens were investigated. Here we identified EtTRAF6 as an important regulator of virus-triggered signaling pathway. Overexpression of EtTRAF6-ORF and truncated forms of EtTRAF6, including EtTRAF6-C (delete the MATH domain), EtTRAF6-N (delete the RING domain) and EtTRAF6-MATH, inhibited IFN-β activity strongly in grouper spleen (GS) cells...
November 3, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27818144/traf6-restricts-p53-mitochondrial-translocation-apoptosis-and-tumor-suppression
#14
Xian Zhang, Chien-Feng Li, Ling Zhang, Ching-Yuan Wu, Lixia Han, Guoxiang Jin, Abdol Hossein Rezaeian, Fei Han, Chunfang Liu, Chuan Xu, Xiaohong Xu, Chih-Yang Huang, Fuu-Jen Tsai, Chang-Hai Tsai, Kounosuke Watabe, Hui-Kuan Lin
Mitochondrial p53 is involved in apoptosis and tumor suppression. However, its regulation is not well studied. Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK. Genotoxic stress reduces this ubiquitination in cytosol by S13/T330 phosphorylation-dependent translocation of TRAF6 from cytosol to nucleus, where TRAF6 also facilitates the K63-linked ubiquitination of nuclear p53 and its transactivation by recruiting p300 for p53 acetylation...
November 17, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27816415/neuroprotective-effects-of-endurance-exercise-against-neuroinflammation-in-mptp-induced-parkinson-s-disease-mice
#15
Yongchul Jang, Jung-Hoon Koo, Insu Kwon, Eun-Bum Kang, Hyun-Seob Um, Hideaki Soya, Youngil Lee, Joon-Yong Cho
Parkinson's disease (PD) is one of the main degenerative neurological disorders accompanying death of dopaminergic neurons prevalent in aged population. Endurance exercise (EE) has been suggested to confer neurogenesis and mitigate the degree of seriousness of PD. However, underlying molecular mechanisms responsible for exercise-mediated neuroprotection against PD remain largely unknown. Given the relevant interplay between elevated α-synuclein and neuroinflammation in a poor prognosis and vicious progression of PD and anti-inflammatory effects of EE, we hypothesized that EE would reverse motor dysfunction and cell death caused by PD...
November 2, 2016: Brain Research
https://www.readbyqxmd.com/read/27813153/traf6-mediates-suppression-of-osteoclastogenesis-and-prevention-of-ovariectomy-induced-bone-loss-by-a-novel-prenylflavonoid
#16
E M Tan, L Li, I R Indran, N Chew, E L Yong
Given the limitations of current therapeutic options for postmenopausal osteoporosis, there is a need for alternatives with minimal adverse effects. In this study, we evaluated the effects of icaritin (ICT), a natural prenylflavonoid, on osteoclastogenesis both in vitro and in an ovariectomized (OVX)-rat model, and investigated its underlying molecular mechanism(s) of action. ICT inhibited osteoclast formation in two osteoclast precursor models, RAW 264.7 mouse monocyte cell line and human PBMC. ICT also inhibited sealing zone and resorption pit formation in a dose-dependent manner...
November 4, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27808398/homozygous-deletion-of-rag1-rag2-and-5-region-traf6-causes-severe-immune-suppression-and-atypical-osteopetrosis
#17
Monika Weisz Hubshman, Lina Basel-Vanagaite, Aviva Krauss, Osnat Konen, Yael Levy, Ben Zion Garty, Pola Smirin-Yosef, Idit Maya, Irina Lagovsky, Ellen Taub, Daphna Marom, Dafna Gaash, Keren Shichrur, Smadar Avigad, Lucille Hayman Manzur, Anna Villa, Cristina Sobacchi, Mordechai Shohat, Isaac Yaniv, Jerry Stein
Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. A biallelic microdeletion encompassing the 5' region of TRAF6, RAG1 and RAG2 genes was identified. TRAF6, a tumor necrosis factor receptor-associated family member, plays an important role in T-cell signaling and in RANKL-dependent osteoclast differentiation and activation but its role in human OP has not been previously reported...
November 3, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27791197/epigallocatechin-3-gallate-egcg-suppresses-melanoma-cell-growth-and-metastasis-by-targeting-traf6-activity
#18
Jianglin Zhang, Zhou Lei, Zunnan Huang, Xu Zhang, Youyou Zhou, Zhongling Luo, Weiqi Zeng, Juan Su, Cong Peng, Xiang Chen
TRAF6 (TNF Receptor-Associated Factor 6) is an E3 ubiquitin ligase that contains a Ring domain, induces K63-linked polyubiquitination, and plays a critical role in signaling transduction. Our previous results demonstrated that TRAF6 is overexpressed in melanoma and that TRAF6 knockdown dramatically attenuates tumor cell growth and metastasis. In this study, we found that EGCG can directly bind to TRAF6, and a computational model of the interaction between EGCG and TRAF6 revealed that EGCG probably interacts with TRAF6 at the residues of Gln54, Gly55, Asp57 ILe72, Cys73 and Lys96...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27768832/articular-cartilage-injury-rapidly-activates-tak1-in-chondrocytes-by-inducing-its-phosphorylation-and-k63-polyubiquitination
#19
Heba M Ismail, Athanasios Didangelos, Tonia L Vincent, Jeremy Saklatvala
Objectives Mechanical injury to cartilage predisposes to osteoarthritis (OA). Wounding the articular cartilage surface causes rapid activation of MAP kinases and NFκB mimicking the response to inflammatory cytokines. Here, we identify the upstream signalling mechanisms involved. Methods Cartilage was injured by dissecting it from the articular surface of porcine metacarpophalangeal joints (MCP) or by avulsing murine proximal femoral epiphyses. Protein phosphorylation was assayed by Western blotting of cartilage lysates...
October 21, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27746020/the-k48-k63-branched-ubiquitin-chain-regulates-nf-%C3%AE%C2%BAb-signaling
#20
Fumiaki Ohtake, Yasushi Saeki, Satoshi Ishido, Jun Kanno, Keiji Tanaka
Polyubiquitin chains of different topologies regulate diverse cellular processes. K48- and K63-linked chains, the two most abundant chain types, regulate proteolytic and signaling pathways, respectively. Although recent studies reported important roles for heterogeneous chains, the functions of branched ubiquitin chains remain unclear. Here, we show that the ubiquitin chain branched at K48 and K63 regulates nuclear factor κB (NF-κB) signaling. A mass-spectrometry-based quantification strategy revealed that K48-K63 branched ubiquitin linkages are abundant in cells...
October 20, 2016: Molecular Cell
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