Read by QxMD icon Read


Daoxiang Zhang, Lin Li, Hongmei Jiang, Brett Knolhoff, Albert C Lockhart, Andrea Wang-Gillam, David DeNardo, Marianna B Ruzinova, Kian-Huat Lim
PURPOSE: Aberrant activation of the NF-κB transcription factors underlies the aggressive behavior and poor outcome of pancreatic ductal adenocarcinoma (PDAC). However, clinically effective and safe NF-κB inhibitors are not yet available. Because NF-κB transcription factors can be activated by the Interleukin-1 Receptor-Associated Kinase (IRAK) downstream of the Toll-like receptors (TLRs), but has not been explored in PDAC, we sought to investigate the role of IRAK in the pathobiology of PDAC...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hua Zhou, Erin Harberts, Rita Fishelevich, Anthony A Gaspari
UVR-induced apoptosis in cutaneous antigen presenting cells (APC) causes systemic immune suppression and is dependent on TLR4/MyD88 signaling, but the apoptotic signaling pathways have not been defined. Macrophages pre-treated with lipopolysaccharide (LPS) were unresponsive to subsequent LPS treatment; however, but were susceptible to UVR-induced apoptosis. Macrophage survival and apoptotic events after UVR were also unaffected by treatment with TLR4 antagonists, a blocking IgG or a TLR4 analog antagonist, suggesting that UVR cell death is independent of a soluble ligand...
September 27, 2016: Experimental Dermatology
Kidong Kang, Minho Won, Jae-Min Yuk, Chan-Yong Park, Hee Sun Byun, Kyeong Ah Park, So-Ra Lee, Young-Goo Kang, Han-Ming Shen, Ill Young Lee, Gang Min Hur
A specific small-molecule inhibitor of the TLR4 signaling complex upstream of the IKK would likely provide therapeutic benefit for NF-κB-mediated inflammatory disease. We previously identified brazilin as a selective upstream IKK inhibitor targeting the Myddosome complex. In this study, using a cell-based ubiquitination assay for IRAK1 and a chemical library comprising a series of structural analogues of brazilin, a novel small molecule, 2-hydroxy-5,6-dihydroisoindolo[1,2-a]isoquinoline-3,8-dione (IinQ), was identified as a selective and potent inhibitor of IRAK1-dependent NF-κB activation upon TLR4 ligation...
September 21, 2016: Biochemical Pharmacology
Yi-Yung Hung, Chin-Chuen Lin, Hong-Yo Kang, Tiao-Lai Huang
Inflammation and abnormalities in Toll-like receptor (TLR) expression and activation have been linked to major depressive disorder (MDD). However, negative regulators of TLR pathways have not been previously investigated in this context. Here, we sought to investigate the association of depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), with mRNA expression levels of negative regulators of the TLR pathway, including SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2 and TNFAIP3, in peripheral blood mononuclear cells (PBMCs) from 100 patients with MDD and 53 healthy controls, before and after treatment with antidepressants...
September 15, 2016: Brain, Behavior, and Immunity
Xinqi Zhong, Yi-Zhou Jiang, Peiwen Liu, Wenzhi He, Zhongtang Xiong, Weijie Chang, Jiandong Zhu, Qiliang Cui
Assisted reproductive technology (ART) is widely used for the women with infertility conditions to achieve pregnancy. However, the adverse effects of ART may lead to poor perinatal and neonatal outcomes, e.g., preterm birth and low body weight. In this study, we investigated the inflammatory molecular factors and microRNA that might be involved in ART related preterm birth. We found the elevation of Toll-like 4 receptor (TLR4), activation of NFκB pathway and down-regulation of microRNA-146a (miR-146a), a negative regulator of NFκB, in the placenta of preterm birth and ART, indicating preterm birth and ART were associated with inflammation signaling activation...
September 12, 2016: Oncotarget
Ning Li, Jinhua Jiang, Jing Fu, Ting Yu, Bibo Wang, Wenhao Qin, An Xu, Mengchao Wu, Yao Chen, Hongyang Wang
BACKGROUND: Interleukin-1 receptor associated kinase 1 (IRAK1), as a down-stream of toll-like receptor (TLR) signaling, plays important roles in series of malignancies. However, the role of IRAK1 in hepatocellular carcinoma (HCC) remains little known. METHODS: In our study, reverse transcription-PCR (RT-PCR), Western Blot, and immunohistochemical staining were used to assess the mRNA and protein levels of IRAK1 in clinical samples and cell lines. Cell counting assay and flow cytometry were employed to analyze the effect of IRAK1 on cell cycle and apoptosis...
2016: Journal of Experimental & Clinical Cancer Research: CR
X-K Yang, P Li, C Zhang, R-X Leng, S Li, J Liu, B-Z Li, H-F Pan, D-Q Ye
BACKGROUND: The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent. AIM: A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association...
August 31, 2016: Zeitschrift Für Rheumatologie
Marie Willems, Nadège Dubois, Lucia Musumeci, Vincent Bours, Pierre A Robe
IκBζ, an atypical member of the nuclear IκB family of proteins, is expressed at low levels in most resting cells, but is induced upon stimulation of Toll-like/IL-1 receptors through an IRAK1/IRAK4/NFκB-dependent pathway. Like its homolog Bcl3, IκBζ can regulate the transcription of a set of inflamatory genes through its association with the p50 or p52 subunits of NF-κB. Long studied as a key component of the immune response, IκBζ emerges as an important regulator of inflammation, cell proliferation and survival...
August 26, 2016: Oncotarget
Eun Ju Im, Su Jung Kim, Seung Bok Hong, Jin-Kyu Park, Man Hee Rhee
Bee venom has long been used as a traditional folk medicine in Korea. It has been reportedly used for the treatment of arthritis, cancer, and inflammation. Although its anti-inflammatory activity in lipopolysaccharide- (LPS-) stimulated inflammatory cells has been reported, the exact mechanism of its anti-inflammatory action has not been fully elucidated. Therefore, the aim of this study was to investigate the anti-inflammatory mechanism of bee venom in BV2 microglial cells. We first investigated whether NO production in LPS-activated BV2 cells was inhibited by bee venom, and further iNOS mRNA and protein expressions were determined...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
K Kamali, E Salmani Korjan, E Eftekhar, K Malekzadeh, F Ghadiri Soufi
Emerging studies have been shown that the expression of micrRNA-146a (miR-146a, as a regulator of nuclear factor κB (NF-κB)), is changed in diabetic patients and animals. This study was designed to evaluate the possible role of miR-146a in the pathogenesis of diabetes-related microvascular complications. Concurrent with the creation of cellular hyperglycemia (25 mmol/L for 24 h), human umbilical vein endothelial cells (HUVECs) were transfected with 20 nmol/L of hsa-miR-146a antagomir or scramble using HiPerFect reagent (Qiagen)...
2016: Bratislavské Lekárske Listy
Matija Hedl, Jie Yan, Clara Abraham
Interferon regulatory factor 5 (IRF5) regulates inflammatory M1 macrophage polarization, and disease-associated IRF5 genetic variants regulate pattern-recognition-receptor (PRR)-induced cytokines. PRR-stimulated macrophages and M1 macrophages exhibit enhanced glycolysis, a central mediator of inflammation. We find that IRF5 is needed for PRR-enhanced glycolysis in human macrophages and in mice in vivo. Upon stimulation of the PRR nucleotide binding oligomerization domain containing 2 (NOD2) in human macrophages, IRF5 binds RIP2, IRAK1, and TRAF6...
August 30, 2016: Cell Reports
Chen-Kai Chou, Shun-Yu Chi, Cai-Hua Huang, Fong-Fu Chou, Chao-Cheng Huang, Rue-Tsuan Liu, Hong-Yo Kang
CONTEXT: MicroRNA (miR)-146b is overexpressed in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal invasion, advanced tumor stage, and poor prognosis. However, the underlying mechanism of miR-146b in relation to its oncogenic behavior in PTC and its putative targets remain unknown. OBJECTIVE: The purpose was to investigate interleukin-1 receptor-associated kinase 1 (IRAK1) as the potential miR-146b target gene and its involvement in PTC. DESIGN: We used genome-wide microarray, computational analysis and 3` UTR reporter gene assays to identify IRAK1 as a miR-146b target gene...
August 17, 2016: Journal of Clinical Endocrinology and Metabolism
Renáta Gáspár, Márton Pipicz, Fatime Hawchar, Dávid Kovács, Luna Djirackor, Anikó Görbe, Zoltán V Varga, Mónika Kiricsi, Goran Petrovski, Attila Gácser, Csaba Csonka, Tamás Csont
AIMS: Exogenously administered biglycan (core protein with high-molecular weight glycosaminoglycan chains) has been shown to protect neonatal cardiomyocytes against simulated ischemia/reperfusion injury (SI/R), however, the mechanism of action is not clear. In this study we aimed to investigate, which structural component of biglycan is responsible for its cardiocytoprotective effect and to further explore the molecular mechanisms involved in the cytoprotection. METHODS AND RESULTS: A pilot study was conducted to demonstrate that both native (glycanated) and deglycanated biglycan can attenuate cell death induced by SI/R in a dose-dependent manner in primary neonatal cardiomyocytes isolated from Wistar rats...
August 9, 2016: Journal of Molecular and Cellular Cardiology
Minakshi Rana, Preeti Maurya, Sukka S Reddy, Vishal Singh, Hafsa Ahmad, Anil K Dwivedi, Madhu Dikshit, Manoj K Barthwal
The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L.) enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect and the underlying mechanism of a novel chemically modified, non-carbonyl compound enriched Curcuma longa L. (C. longa) extract (CMCE). CMCE (1 or 10 μg/mL; 14 h) significantly decreased LPS (50-100 ng/mL) induced TNF-α and IL-1β production in THP-1 cells, human, and mouse whole blood as measured by ELISA...
2016: Frontiers in Pharmacology
Tina L Samuels, Justin Yan, Pawjai Khampang, Alexander MacKinnon, Wenzhou Hong, Nikki Johnston, Joseph E Kerschner
OBJECTIVE: Toll-like receptor signaling activated by bacterial otitis media pathogens in the middle ear has been shown to play a key role in OM susceptibility, pathogenesis and recovery. Recent studies implicate microRNA 146 (miR-146) in regulation of inflammation via negative feedback of toll-like receptor signaling (TLR) in a wide variety of tissues, however its involvement in otitis media is unknown. METHODS: Human middle ear epithelial cells were stimulated with proinflammatory cytokines, interleukin 1 beta or tumor necrosis factor alpha, for two to twenty-four hours...
September 2016: International Journal of Pediatric Otorhinolaryngology
Tiberio Sticca, Jean-Hubert Caberg, Stephane Wenric, Christophe Poulet, Christian Herens, Mauricette Jamar, Claire Josse, Sonia El Guendi, Stéphanie Max, Yves Beguin, André Gothot, Jo Caers, Vincent Bours
The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis non-hyperdiploid group with a higher incidence of IgH translocations. This classification, however, is inadequate and many other parameters like mutations, epigenetic modifications and genomic heterogeneity may influence the prognosis. We performed a genomic study by array-based comparative genomic hybridization (aCGH) on a cohort of 162 patients to evaluate the frequency of genomic gains and losses...
July 25, 2016: Genes, Chromosomes & Cancer
Xiaozhe Fu, Qiang Lin, Lihui Liu, Hongru Liang, Zhibin Huang, Ningqiu Li
Co-infection with infectious spleen and kidney necrosis virus (ISKNV) and Aeromonas hydrophila is becoming ever more widespread in Chinese perch (Siniperca chuatsi) aquaculture industry, so that it's necessary to develop the combined vaccine against ISKNV and A. hydrophila disease. The surface display of heterologous on bacteria using anchoring motifs from outer membranes proteins has already been explored as an effective delivery system of viral antigens. In present study, the ISKNV orf086 gene, which is verified as a protective antigen, was inserted into ompA gene cassette of A...
September 2016: Fish & Shellfish Immunology
Haichong Wu, Gan Zhao, Kangfeng Jiang, Chengye Li, Changwei Qiu, Ganzhen Deng
Engeletin (dihydrokaempferol 3-rhamnoside) is a flavanonol glycoside. It can be found in the skin of white grapes and white wine and is widely distributed in southeast Asia, and the leaves are used in a tea. Here, we explored the impact of engeletin against the inflammatory reaction in a lipopolysaccharide (LPS)-induced endometritis mouse model. Engeletin treatment significantly attenuated uterus damage and decreased myeloperoxidase activity. ELISA and qPCR assays showed that engeletin dose-dependently suppressed the expression of TNF-α, IL-1β, and IL-6...
August 10, 2016: Journal of Agricultural and Food Chemistry
Jaya Talreja, Harvinder Talwar, Nisar Ahmad, Ruchi Rastogi, Lobelia Samavati
Sarcoidosis is a multisystem granulomatous disease of unknown etiology that primarily affects the lungs. Our previous work indicates that activation of p38 plays a pivotal role in sarcoidosis inflammatory response. Therefore, we investigated the upstream kinase responsible for activation of p38 in sarcoidosis alveolar macrophages (AMs) and PBMCs. We identified that sustained p38 phosphorylation in sarcoidosis AMs and PBMCs is associated with active MAPK kinase 4 but not with MAPK kinase 3/6. Additionally, we found that sarcoidosis AMs exhibit a higher expression of IRAK1, IRAK-M, and receptor interacting protein 2 (Rip2)...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yuhan Chen, Zhaochong Zeng, Xiaoyun Shen, Zhifeng Wu, Yinying Dong, Jason Chia-Hsien Cheng
Lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway is demonstrated to be involved in the hepatic fibrosis. MicroRNA (miR)-146a-5p is a key regulator of the innate immune response. The functional significance of miR-146a-5p during the LPS/TLR4 mediated hepatic fibrosis process remains unclear. In this study, we found that TLR4 and α-smooth muscle actin (α-SMA) were up-regulated and miR-146a-5p was down-regulated in human hepatic stellate cell (HSC) line LX2 after LPS stimulation. Overexpression of miR-146a-5p inhibited LPS induced pro-inflammatory cytokines secretion through down-regulating the expression levels of TLR-4, IL-1 receptor-associated kinase 1 (IRAK1), TNF receptor associated factor-6 (TRAF6) and phosphorylation of nuclear factor-kappa B (NF-κB)...
2016: International Journal of Molecular Sciences
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"