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https://www.readbyqxmd.com/read/29119451/pristimerin-inhibits-lps-triggered-neurotoxicity-in-bv-2-microglia-cells-through-modulating-irak1-traf6-tak1-mediated-nf-%C3%AE%C2%BAb-and-ap-1-signaling-pathways-in-vitro
#1
Bin Hui, Liping Zhang, Qinhua Zhou, Ling Hui
Microglia plays a prominent role in the brain's inflammatory response to injury or infection by migrating to affected locations and secreting inflammatory molecules. However, hyperactivated microglial is neurotoxic and plays critical roles in the pathogenesis of neurodegenerative diseases. Pristimerin, a naturally occurring triterpenoid, possesses antitumor, antioxidant, and anti-inflammatory activities. However, the effect and the molecular mechanism of pristimerin against lipopolysaccharide (LPS)-induced neurotoxicity in microglia remain to be revealed...
November 8, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29115455/dioscin-inhibits-ischemic-stroke%C3%A2-induced-inflammation-through-inhibition-of-the-tlr4-myd88-nf%C3%A2-%C3%AE%C2%BAb-signaling-pathway-in-a-rat-model
#2
Shilin Zhu, Siyuan Tang, Feng Su
Diosgenin, as an essential natural steroidal saponin, can be extracted from numerous sources, primarily from fenugreek. It is an important raw material for the synthesis of steroid hormone drugs. It exhibits antitumor, anti‑inflammatory, antioxidation and several other significant pharmacologic actions, and is of high pharmaceutical value. In the present study, the activities and underlying mechanisms of dioscin in the inhibition of ischemic stroke in rats were investigated. Inflammatory responses wer analyzed using ELISA kits and caspase‑3 and caspase‑9 activity was analyzed using Caspase‑3 and caspase‑9 activity kits...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29058209/the-rs2910164-variant-is-associated-with-reduced-mir-146a-expression-but-not-cytokine-levels-in-patients-with-type-2-diabetes
#3
B Alipoor, H Ghaedi, R Meshkani, M D Omrani, Z Sharifi, T Golmohammadi
PURPOSE: Previous reports have demonstrated that genetic variations in microRNAs regulome could affect microRNAs-mediated regulation. Therefore, in the present study we were aimed at (1) comparison of microRNA 146-a (miR-146a) peripheral blood mononuclear cells (PBMCs) and plasma levels between diabetic patients and controls, and (2) investigating the possible association of rs2910164 with miR-146a and its related target genes expression and also serum cytokine levels. METHODS: The study population consisted of 60 subjects including 30 type 2 diabetes (T2D) patients and 30 controls with determined genotypes for rs2910164...
October 22, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29058172/the-expression-of-dectin-1-irak1-and-rip2-during-the-host-response-to-aspergillus-fumigatus
#4
Jinguo Liu, Lin Yu, Cuicui Chen, Jian Zhou, Xin Gong, Dandan Li, Dongni Hou, Yuanlin Song, Changzhou Shao
BACKGROUND: C-type lectin receptors (CLRs), Toll-like receptors (TLRs), and Nod-like receptors (NLRs) have the ability to recognize Aspergillus fumigatus (A. fumigates) and induce innate immune response. Dectin-1 is a well-described CLR, while interleukin-1 receptor-associated kinase 1 (Irak1) and receptor-interacting protein 2 (Rip2) are pivotal adaptor proteins of TLRs and NLRs signaling pathways, respectively. OBJECTIVES: Our primary aim is to elucidate whether Dectin-1 regulates the expression of Irak1 and Rip2, and confirm that CLRs, TLRs, and NLRs pathways act synergistically in response to A...
October 23, 2017: Mycopathologia
https://www.readbyqxmd.com/read/29048684/mir-146a-and-mir-146b-in-the-diagnosis-and-prognosis-of-papillary-thyroid-carcinoma
#5
Zhenwei Qiu, Hai Li, Jianwei Wang, Chongbing Sun
The present study investigated the relationship between the expression of miR-146a and miR‑146b with the occurrence and prognosis of papillary thyroid carcinoma. Experiments in vitro were also used to explore the effect of the knocked down expression of the miRNAs on growth and migration of papillary thyroid carcinoma cells. A total of 73 patients with papillary thyroid carcinoma admitted to Yidu Central Hospital of Weifang from September 2013 to September 2015 were enrolled in the study. Carcinoma samples were obtained from each patient, and adjacent tissues were used as control samples to determine expression levels of miR-146a and miR146b by semi-quantitative RT-PCR...
September 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29038250/inhibition-of-irak1-ubiquitination-determines-glucocorticoid-sensitivity-for-tlr9-induced-inflammation-in-macrophages
#6
Fansheng Kong, Zhiwei Liu, Viral G Jain, Kenjiro Shima, Takuji Suzuki, Louis J Muglia, Daniel T Starczynowski, Chandrashekhar Pasare, Sandip Bhattacharyya
Inflammatory responses are controlled by signaling mediators that are regulated by various posttranslational modifications. Recently, transcription-independent functions for glucocorticoids (GC) in restraining inflammation have emerged, but the underlying mechanisms are unknown. In this study, we report that GC receptor (GR)-mediated actions of GC acutely suppress TLR9-induced inflammation via inhibition of IL-1R-associated kinase 1 (IRAK1) ubiquitination. β-TrCP-IRAK1 interaction is required for K48-linked ubiquitination of IRAK1 at Lys(134) and subsequent membrane-to-cytoplasm trafficking of IRAK1 interacting partners TNFR-associated factor 6 and TAK1 that facilitates NF-κB and MAPK activation...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29028369/toll-like-receptors-significance-ligands-signaling-pathways-and-functions-in-mammals
#7
Mallenahally Kusha Vidya, V Girish Kumar, Veerasamy Sejian, Madiajagan Bagath, Govindan Krishnan, Raghavendra Bhatta
This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity...
October 13, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/29017654/-therapeutic-effect-of-hesperidin-on-severe-acute-pancreatitis-in-rats-and-its-mechanism
#8
Min Li, Zhisong Guo, Huanzhang Shao, Bingyu Qin
OBJECTIVE: To investigate the protective effect of hesperidin on severe acute pancreatitis (SAP) in rats and its related mechanism. METHODS: Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups (n = 12 in each group): sham group, SAP model group, dexamethasone group (5 mg/kg), low and high dose of hesperidin groups (10 mg/kg and 20 mg/kg). SAP rats were administered a retrograde infusion of 3.5% sodium taurocholate solution into the biliopancreatic duct after laparotomy...
October 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28981114/essential-role-of-hcmv-deubiquitinase-in-promoting-oncogenesis-by-targeting-anti-viral-innate-immune-signaling-pathways
#9
Puja Kumari, Irene Saha, Athira Narayanan, Sathish Narayanan, Akinori Takaoka, Nachimuthu Senthil Kumar, Prafullakumar Tailor, Himanshu Kumar
Cancer is a multifactorial disease and virus-mediated carcinogenesis is one of the crucial factors, which is poorly understood. Human cytomegalovirus (HCMV) is a herpesvirus and its components have been evidenced to be associated with cancer of different tissue origin. However, its role in cancer remains unknown. Here, we identified a conserved herpesviral tegument protein known as pUL48 of HCMV, encoding deubiquitinase enzyme, as having a key role in carcinogenesis. We show using deubiquitinase sufficient- and deficient-HCMV that HCMV deubiquitinase is a key in inducing enhanced cellular metabolic activity through upregulation of several anti-apoptotic genes and downregulation of several pro-apoptotic genes expression...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28980703/interleukin-1-receptor-associated-kinase-1-correlates-with-metastasis-and-invasion-in-endometrial-carcinoma
#10
Yilin Wang, Yanyan Wang, Xianzhi Duan, Yinuo Wang, Zhenyu Zhang
Endometrial carcinoma (EC) is one of the most common malignancies in the world. Previous studies have investigated the altered expression of interleukin-1 receptor-associated kinase 1 (IRAK1) in various cancers. We aimed at exploring the biological function and the underlying molecular mechanism of IRAK1 in EC. In this study, IRAK1 was found elevated in EC compared with normal tissues. Further, high IRAK1 expression level was correlated with higher tumor stage, lymph node metastasis, myometrial invasion and lower survival rate...
October 5, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28967919/chromosome-1q21-3-amplification-is-a-trackable-biomarker-and-actionable-target-for-breast-cancer-recurrence
#11
Jian Yuan Goh, Min Feng, Wenyu Wang, Gokce Oguz, Siti Maryam J M Yatim, Puay Leng Lee, Yi Bao, Tse Hui Lim, Panpan Wang, Wai Leong Tam, Annette R Kodahl, Maria B Lyng, Suman Sarma, Selena Y Lin, Alexander Lezhava, Yoon Sim Yap, Alvin S T Lim, Dave S B Hoon, Henrik J Ditzel, Soo Chin Lee, Ern Yu Tan, Qiang Yu
Tumor recurrence remains the main reason for breast cancer-associated mortality, and there are unmet clinical demands for the discovery of new biomarkers and development of treatment solutions to benefit patients with breast cancer at high risk of recurrence. Here we report the identification of chromosomal copy-number amplification at 1q21.3 that is enriched in subpopulations of breast cancer cells bearing characteristics of tumor-initiating cells (TICs) and that strongly associates with breast cancer recurrence...
November 2017: Nature Medicine
https://www.readbyqxmd.com/read/28964808/acanthoic-acid-protectsagainst-ethanol-induced-liver-injury-possible-role-of-ampk-activation-and-irak4-inhibition
#12
You-Li Yao, Xin Han, Jian Song, Jing Zhang, Ya-Mei Li, Li-Hua Lian, Yan-Ling Wu, Ji-Xing Nan
The aim of this study was to investigate the effects of acanthoic acid (AA) on the regulation of inflammatory response, lipid accumulation, and fibrosis via AMPK- IRAK4 signaling against chronic alcohol consumption in mice. Ethanol-induced liver injury was induced in male mice by Lieber-DeCarli diet for 28d. And mice in AA groups were gavaged with AA (20 or 40mg/kg) for 28d. AA treatment significantly decreased serum AST and TG, hepatic TG levels, serum ethanol and LPS levels compared with chronic ethanol administration...
November 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28958208/copper-zinc-loaded-montmorillonite-influences-intestinal-integrity-the-expression-of-genes-associated-with-inflammation-tlr4-myd88-and-tgf-%C3%AE-1-signaling-pathways-in-weaned-pigs-after-lps-challenge
#13
Lefei Jiao, Chun Chun Wang, Huan Wu, Rong Gong, Fang Hui Lin, Jie Feng, Caihong Hu
This study was aimed at investigating whether dietary copper/zinc-loaded montmorillonite (Cu/Zn-Mt) could alleviate Escherichia coli LPS-induced intestinal injury through pro- and anti-inflammatory signaling pathways (TLRs, NLRs and TGF-β1) in weaned piglets. Eighteen 21-d-old pigs were randomly divided into three groups (control, LPS and LPS + Cu/Zn-Mt). After 21 d of feeding, pigs in the LPS group and LPS + Cu/Zn-Mt group received i.p. administration of LPS, whereas pigs in the control group received saline...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28954388/pretreatment-of-pam3csk4-attenuates-inflammatory-responses-caused-by-systemic-infection-of-methicillin-resistant-staphylococcus-aureus-in-mice
#14
Zhaoxia Huang, Xiayu Yi, Yiguo Chen, Xiaorui Hou, Xiangyu Wang, Ping Zhu, Kangmin Zhao, Shuangshuang Wu, Ning Fu, Beiyi Liu
Pam3CSK4 is a synthetic tripalmitoylated lipopeptide that acts as a ligand of TLR1/TLR2 by mimicking the acetylated amino terminus of bacterial lipoproteins. Here we found that pretreatment of Pam3CSK4 protected mice from systemic infection of methicillin-resistant Staphylococcus aureus (MRSA), and enhanced the bacterial clearance in bacteremia model. Pro-inflammatory cytokines, such as TNF-α, IL-6, MCP-1 and IFN-γ were significantly decreased in serum from Pam3CSK4-treated mice. Besides, upon PamCSK4 treatment, the TLR2 expression was down-regulated, IRAK1 phosphorylation was inhibited, and the expression of IRAK-M and Tollip, two negative regulators of NF-κB pathway, was up-regulated...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28882891/identification-of-optineurin-as-an-interleukin-1-receptor-associated-kinase-1-binding-protein-and-its-role-in-regulation-of-myd88-dependent-signaling
#15
Mitsuyoshi Tanishima, Shigeo Takashima, Arata Honda, Daisuke Yasuda, Takashi Tanikawa, Satoshi Ishii, Takashi MaruYama
Upon stimulation of toll-like receptors with various microbial ligands, induction of a variety of inflammatory genes is elicited by activation of a myeloid differentiation primary-response protein 88 (MyD88)-dependent signaling pathway. Interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) plays an essential role in this pathway by activating nuclear factor κB (NF-κB) and mitogen-activated kinases (MAPKs). Here, we identified optineurin (OPTN) as an IRAK1-binding protein by yeast two-hybrid screening using IRAK1 as bait...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28877954/suppression-of-toll-like-receptor-2-mediated-proinflammatory-responses-by-mycobacterium-tuberculosis-protein-rv3529c
#16
Upasana Bandyopadhyay, Attinder Chadha, Priya Gupta, Brijendra Tiwari, Kausik Bhattacharyya, Sonam Popli, Rajagopal Raman, Vani Brahamachari, Yogendra Singh, Pawan Malhotra, Krishnamurthy Natarajan
Microorganisms are known to devise various strategies to thwart protective responses by the host. One such strategy is to incorporate sequences and domains in their genes/proteins that have similarity to various domains of the host proteins. In this study, we report that Mycobacterium tuberculosis protein Rv3529c exhibits significant similarity to the death domain of the TLR pathway adaptor protein MyD88. Incubation of macrophages with Rv3529c specifically inhibited TLR2-mediated proinflammatory responses. This included attenuated oxidative burst, reduced phosphorylation of MAPK-ERK, reduced activation of transcription factor NF-κB and reduced secretion of proinflammatory cytokines IFN-γ, IL-6, and IL-17A with a concomitant increased secretion of suppressor cytokines IL-10 and TGF-β...
November 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28858844/can-regular-moderate-exercise-lead-to-changes-in-mirna-146a-and-its-adapter-proteins-in-the-kidney-of-streptozotocin-induced-diabetic-male-rats
#17
H Oghbaei, N Ahmadi Asl, F Sheikhzadeh
OBJECTIVE: The aim of this study was to assess whether microRNA-146a and its adapter proteins TNF receptor associated factor6 (TRAF6) and interleukin-1 receptor-associated kinase-1 (IRAK1) may be changed in the kidney of streptozotocin-induced diabetic rats, following regular moderate exercise. METHODS: Forty adult male Wistar rats were allocated randomly into four groups (n=10), including sedentary control (SC), sedentary diabetic (SD), healthy sixty-day exercise (H60E), and diabetic sixty-day exercise (D60E) groups...
July 1, 2017: Endocrine Regulations
https://www.readbyqxmd.com/read/28844021/tlr2-tlr3-and-tlr5-regulation-of-pro-inflammatory-and-pro-labour-mediators-in-human-primary-myometrial-cells
#18
Ratana Lim, Gillian Barker, Martha Lappas
Preterm birth continues to be a significant global health care issue, due to our lack of understanding of the mechanisms that drive human labour and delivery. Toll-like receptors (TLRs) are essential in triggering an inflammatory response in human gestational tissues, leading to the production of pro-inflammatory and pro-labour mediators, and thus preterm birth. The aims of this study were to determine whether the adaptor molecules associated with TLR2, TLR3 and TLR5 signalling are involved in human myometrium...
August 24, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28811005/regulatory-effects-of-mir-146a-b-on-the-function-of-endothelial-progenitor-cells-in-acute-ischemic-stroke-in-mice
#19
Zeng-Feng Su, Zhong-Wu Sun, Ying Zhang, Shu Wang, Qi-Gui Yu, Ze-Bing Wu
The study aims to explore how microRNA-146a/b (miR-146a/b) regulates the function of endothelial progenitor cells (EPCs) in acute ischemic stroke in mice. Eighty male SPF C57BL/6J mice were evenly divided into the model-6 h, model-12 h, model-24 h (mice suffered from middle cerebral artery occlusion [MCAO] for 6 h, 12 h and model-24 h) and normal groups. EPCs were transfected and assigned into the control, MCAO, MCAO-miR-146a, MCAO-miR-146b and MCAO-miR-146a/b groups. The qRT-PCR was used to detect miR-146a/b expression in EPCs...
August 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28780618/upregulated-irak1-and-irak4-promoting-the-production-of-ifn-%C3%AE-and-il-17-in-behcet-s-disease
#20
Min Sun, Peizeng Yang, Yan Yang, Jian Ye
PURPOSE: To investigate the expression and function of IRAK1 and IRAK4 involved in the development of Behcet's disease. METHODS: Twenty-eight Behcet's patients and thirty-two normal subjects were involved in this study. The mRNA levels of IRAK1 and IRAK4 from active Behcet's patients, inactive Behcet's patients and normal controls were detected using real-time quantitative PCR. CD4(+)T cells were extracted from peripheral blood mononuclear cells of active Behcet's patients and normal controls...
August 5, 2017: International Ophthalmology
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