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Shuying He, Weihong Guo, Feihong Deng, Kequan Chen, Yonghong Jiang, Minyu Dong, Liang Peng, Xueqing Chen
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine-choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b-/- mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA...
March 21, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Quan-Bo Zhang, Yu-Feng Qing, Cong-Cong Yin, Li Zhou, Xian-Shuang Liu, Qing-Sheng Mi, Jing-Guo Zhou
BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of inflammatory and immune responses and are implicated in several immune disorders including gouty arthritis. The expression of miR-146a is upregulated in the peripheral blood mononuclear cells of patients with inter-critical gout when compared to normouricemic and hyperuricemic controls and those patients with acute gout flares. However, the role of miR-146a in the development of gout remains unknown. Here, we used miR-146a knockout (KO) mice to test miR-146a function in a monosodium urate (MSU)-induced gouty arthritis model...
March 15, 2018: Arthritis Research & Therapy
Bo Chu, Yadong Zhou, Heng Zhai, Lei Li, Li Sun, Yun Li
MicroRNA-146a (miR-146a) is reportedly implicated in the pathogenesis of ischemia/reperfusion (I/R) injury. Its role in the cerebral I/R injury is however unclear and requires further investigation. In this study, cerebral I/R injury was established in mice via middle cerebral artery occlusion (MCAO), and the expression of miR-146a was detected in the brain tissue via quantitative real-time PCR. We found that the expression of miR-146a was up-regulated. Furthermore, the endogenous miR-146a was antagonized by its specific inhibitor...
March 5, 2018: Canadian Journal of Physiology and Pharmacology
Bowie Y Cheng, Eunice Y Lau, Hoi-Wing Leung, Carmen Oi-Ning Leung, Nicole P Ho, Shilpa Gurung, Lily K Cheng, Chi Ho Lin, Regina Cheuk-Lam Lo, Stephanie Ma, Irene Oi-Lin Ng, Terence K Lee
Frequent relapse and drug resistance in patients with hepatocellular carcinoma (HCC) can be attributed to the existence of tumor-initiating cells (T-IC) within the tumor bulk. Therefore, targeting liver T-IC may improve the prognosis of these patients. From transcriptome sequencing of 16 pairs of clinical HCC samples, we report that interleukin-1 receptor-associated kinase 1 (IRAK1) in the TLR/IRAK pathway is significantly upregulated in HCC. IRAK1 overexpression in HCC was further confirmed at the mRNA and protein levels and correlated with advanced tumor stages and poor patient survival...
February 26, 2018: Cancer Research
(no author information available yet)
[This corrects the article on p. 8025 in vol. 12, PMID: 29184402.].
2018: International Journal of Nanomedicine
Jing Zhang, Chunbo Yu, Xuan Zhang, Huiwen Chen, Jiachen Dong, Weili Lu, Zhongchen Song, Wei Zhou
BACKGROUND: Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) is one of the major pathogenic factors of chronic periodontitis (CP). Few reports on the correlation between P. gingivalis-LPS and cognitive function exist. Thus, the present study aimed to investigate the effects of P. gingivalis-LPS on cognitive function and the associated underlying mechanism in C57BL/6 mice. METHODS: The C57BL/6 mice were injected with P. gingivalis-LPS (5 mg kg-1) either with or without Toll-like receptor 4 (TLR4) inhibitor (TAK-242, 5 mg kg-1)...
February 9, 2018: Journal of Neuroinflammation
Yoko Ito, Niccolette Schaefer, Amelia Sanchez, David Francisco, Rafeul Alam, Richard J Martin, Julie G Ledford, Connor Stevenson, Di Jiang, Liwu Li, Monica Kraft, Hong Wei Chu
Toll-interacting protein (Tollip) is a key negative regulator of innate immunity by preventing excessive proinflammatory responses. Tollip genetic variation has been associated with airflow limitation in asthma subjects and Tollip expression. Whether Tollip regulates lung inflammation in a type 2 cytokine milieu (e.g., IL-13) is unclear. Our goal was to determine the in vivo role of Tollip in IL-13-mediated lung eosinophilic inflammation and the underlying mechanisms. Tollip-knockout (KO) and wild-type (WT) mice were inoculated intranasally with recombinant mouse IL-13 protein to examine lung inflammation...
January 27, 2018: Journal of Innate Immunity
Yue Hu, Liang Hu, Desheng Gong, Hanlin Lu, Yue Xuan, Ru Wang, De Wu, Daiwen Chen, Keying Zhang, Fei Gao, Lianqiang Che
Intrauterine growth restriction (IUGR) may elicit a series of postnatal body developmental and metabolic diseases due to their impaired growth and development in the mammalian embryo/fetus during pregnancy. In the present study, we hypothesized that IUGR may lead to abnormally regulated DNA methylation in the intestine, causing intestinal dysfunctions. We applied reduced representation bisulfite sequencing (RRBS) technology to study the jejunum tissues from four newborn IUGR piglets and their normal body weight (NBW) littermates...
February 1, 2018: Molecular Genetics and Genomics: MGG
Yuhan Chen, Zhifeng Wu, Baoying Yuan, Yinying Dong, Li Zhang, Zhaochong Zeng
Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4 and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2. Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS-induced pro-inflammatory cytokine secretion and cell proliferation, and promoted cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1 receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B...
January 18, 2018: Cell Death & Disease
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...
March 2018: American Journal of Medical Genetics. Part A
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
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
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
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 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
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
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
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
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...
January 2018: Molecular Medicine Reports
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
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
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