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https://www.readbyqxmd.com/read/29341460/intellectual-disability-and-epilepsy-due-to-the-k-l-mediated-xq28-duplication-further-evidence-of-a-distinct-dosage-dependent-phenotype
#1
David Isum Ward, Bethany A Buckley, Eyby Leon, Jullianne Diaz, Margaret Faust Galegos, Sean Hofherr, Amy Feldman Lewanda
Copy number variants of the X-chromosome are a common cause of X-linked intellectual disability in males. Duplication of the Xq28 band has been known for over a decade to be the cause of the Lubs X-linked Mental Retardation Syndrome (OMIM 300620) in males and this duplication has been narrowed to a critical region containing only the genes MECP2 and IRAK1. In 2009, four families with a distal duplication of Xq28 not including MECP2 and mediated by low-copy repeats (LCRs) designated "K" and "L" were reported with intellectual disability and epilepsy...
January 17, 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29337240/prevention-of-the-severity-of-post-ischemic-inflammation-and-brain-damage-by-simultaneous-knockdown-of-toll-like-receptors-2-and-4
#2
Koteswara Rao Nalamolu, Nathan J Smith, Bharath Chelluboina, Jeffrey D Klopfenstein, David M Pinson, David Z Wang, Raghu Vemuganti, Krishna Kumar Veeravalli
Toll-like receptor 2 (TLR2) and TLR4 belong to a family of highly conserved pattern recognition receptors and are well-known upstream sensors of signaling pathways of innate immunity. TLR2 and TLR4 upregulation is thought to be associated with poor outcome in stroke patients. We currently show that transient focal ischemia in adult rats induces TLR2 and TLR4 expression within hours and shRNA-mediated knockdown of TLR2 and TLR4 alone and in combination decreases the infarct size and swelling. We further show that TLR2 and TLR4 knockdown also prevented the induction of their downstream signaling molecules MyD88, IRAK1, and NFκB p65 as well as the pro-inflammatory cytokines IL-1β, IL-6, and TNFα...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29288795/mir-146a-regulates-inflammatory-cytokine-production-in-porphyromonas-gingivalis-lipopolysaccharide-stimulated-b-cells-by-targeting-irak1-but-not-traf6
#3
Shaoyun Jiang, Yang Hu, Shu Deng, Jiayin Deng, Xinbo Yu, Grace Huang, Toshihisa Kawai, Xiaozhe Han
It has been suggested that microRNAs (miRs) are involved in the immune regulation of periodontitis. However, it is unclear whether and how miRs regulate the function of B cells in the context of periodontitis. This study is to explore the role of miR-146a on the inflammatory cytokine production of B cells challenged by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). Primary B cells were harvested from mouse spleen. Quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of inflammatory cytokines in B cells in the presence or absence of P...
December 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29235894/pacritinib-and-its-use-in-the-treatment-of-patients-with-myelofibrosis-who-have-thrombocytopenia
#4
Adolfo Enrique Diaz, Ruben A Mesa
The treatment landscape for myelofibrosis (MF) has reached the molecular era by targeting different pathways that are implied in this myeloproliferative neoplasm. A few years ago, the first-in-class JAK1/JAK2 inhibitor ruxolitinib, demonstrated reductions in both constitutional symptoms and splenomegaly, leading to the US FDA approval. The development or worsening of cytopenias in patients receiving ruxolitinib uncovered an unmet need that has been addressed by alternative approaches. Pacritinib, a dual JAK2 and FLT3 inhibitor which also inhibits IRAK1, has demonstrated the ability to favorably impact MF-associated splenomegaly and symptom burden, while having limited myelosuppression with manageable gastrointestinal toxicity...
December 13, 2017: Future Oncology
https://www.readbyqxmd.com/read/29208712/crystal-structure-of-human-irak1
#5
Li Wang, Qi Qiao, Ryan Ferrao, Chen Shen, John M Hatcher, Sara J Buhrlage, Nathanael S Gray, Hao Wu
Interleukin 1 (IL-1) receptor-associated kinases (IRAKs) are serine/threonine kinases that play critical roles in initiating innate immune responses against foreign pathogens and other types of dangers through their role in Toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) mediated signaling pathways. Upon ligand binding, TLRs and IL-1Rs recruit adaptor proteins, such as myeloid differentiation primary response gene 88 (MyD88), to the membrane, which in turn recruit IRAKs via the death domains in these proteins to form the Myddosome complex, leading to IRAK kinase activation...
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29204872/anti-inflammatory-effects-of-rosmarinic-acid-in-lipopolysaccharide-induced-mastitis-in-mice
#6
Kangfeng Jiang, Xiaofei Ma, Shuai Guo, Tao Zhang, Gan Zhao, Haichong Wu, Xiaoyan Wang, Ganzhen Deng
Rosmarinic acid (RA), a type of food additives mainly extracted from rosemary, has been reported to possess anti-inflammatory activities in some previous studies. However, the effects of RA on lipopolysaccharide (LPS)-induced mastitis have not been reported. Here, we investigated the anti-inflammatory effects of RA on LPS-induced mastitis in mice and elucidated the potential mechanisms in mouse mammary epithelial cells (mMECs). RA treatment significantly ameliorated the mammary structural damage, and reduced the activity of myeloperoxidase...
December 4, 2017: Inflammation
https://www.readbyqxmd.com/read/29184402/cooperation-of-irak1-4-inhibitor-and-abt-737-in-nanoparticles-for-synergistic-therapy-of-t-cell-acute-lymphoblastic-leukemia
#7
Xiaoyan Wu, Lin Wang, Yining Qiu, Bingyu Zhang, Zhenhua Hu, Runming Jin
T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology...
2017: International Journal of Nanomedicine
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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