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Anti-inflammatory effects of traditional mixed extract of medicinal herbs(MEMH)on monosodium urate crystal-induced gouty arthritis

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Chinese Journal of Natural Medicines 2017年第8期15卷 561-575页

作者： Ju-Suk Nam Supriya Jagga Ashish Ranjan Sharma Joon-Hee Lee Jong Bong Park Jun-Sub Jung Sang-Soo Lee Institute For Skeletal Aging&Orthopedic Surgery Hallym University-Chuncheon Sacred Heart HospitalChuncheonGangwon-do24252Republic of Korea Institute of Natural Medicine College of MedicineHallym UniversityChucheonGangwon-do 24252Republic of Korea Hana Oriental Clinic ChucnheonGangwon-do 24433Republic of Korea

Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs(MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate(MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mR NA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaO S-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators(IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mR NA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis.

关键词： Gout monosodium urate crystals Inflammation Chondrocyte Oriental medicine

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Suppression of monosodium urate crystal-induced inflammation by inhibiting TGF-β-activated kinase 1-dependent signaling:role of the ubiquitin proteasome system

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Cellular & Molecular Immunology 2021年第1期18卷 162-170页

作者： Anil K.Singh Mahamudul Haque Kayla O'Sullivan Mukesh Chourasia Madhu M.Ouseph Salahuddin Ahmed Department of Pharmaceutical Sciences Washington State University College of PharmacySpokaneWAUSA Center for Computational Biology and Bioinformatics Amity Institute of BiotechnologyAmity UniversityNoidaUttar PradeshIndia Department of Pathology Stanford University School of MedicineStanfordCAUSA Division of Rheumatology University of Washington School of MedicineSeattleWAUSA

monosodium urate(MSU)crystals activate inflammatory pathways that overlap with interleukin-1β(IL-1β)***,the post-translational mechanisms involved and the role of signaling proteins in this activation are *** the present study,we investigated the intracellular signaling mechanisms involved in MSU-induced activation of THP-1 macrophages and human nondiseased synovial fibroblasts(NLSFs)and the in vivo efficacy of an inhibitor of tumor grovArth factor-β(TGF-β)-activated kinase 1(TAK1),5Z-7-oxozeaenoI,in MSU-induced paw inflammation in C57BL76 ***-1 macrophage activation with MSU crystals(25-200 ng/ml)resulted in the rapid and sustained phosphorylation of interleukin-1 receptor-activated kinase 1(IRAK1 Thr^(209))and TAK1(Thr^(184/187))and their association with the E3 ubiquitin ligase *** the cellular level,MSU inhibited the deubiquitinases A20 and UCHL2 and increased 20s proteasomal activity,leading to a global decrease in K^(63)-linked ubiquitination and increase in K^(48)-linked ubiquitination in THP-1 *** MSU did not stimulate cytokine produaion in NLSFs,it significantly amplified IL-1β-induced IL-6,IL-8,and ENA-78/CXCL5 *** studies and MD simulations followed by TAK1 in vitro kinase assays revealed that uric acid molecules are capable of arresting TAK1 in an active-state conformation,resulting in sustained TAK1 kinase ***,MSU-induced proinflammatory cytokine production was completely inhibited by 5Z-7-oxozeaenol but not IRAK1/4 or TRAF6 *** of 5Z-7-oxozeaenol(5 or 15 mg/kg;orally)significantly inhibited MSU-induced paw inflammation in C57BL/6 *** study identifies a novel post-translational mechanism of TAK1 activation by MSU and suggests the therapeutic potential of TAK1 in regulating MSU-induced Inflammation.

关键词： monosodium urate crystals Gout TAK1 Ubiquitination 5Z-7-oxozeaenol

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Case Report: Gouty Tophus of the Larynx

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International Journal of Otolaryngology and Head & Neck Surgery 2021年第1期10卷 43-48页

作者： Chung-Yu Hao Yih-Jeng Tsai Hsing-Mei Wu Chia-Jung Lee Department of Otolaryngology Head and Neck Surgery Shin Kong Wu Ho-Su Memorial Hospital Taiwan College of Medicine Fu Jen Catholic University Taiwan

Gout is a metabolic disorder that is characterized by a deposition of monosodium urate crystals in the joint or soft tissue. Gout manifestations in head and neck region are rare, and larynx is an infrequently affected location. We recently managed a case of a gouty tophus over the larynx. A 65-year-old male with a long history of gout without medical control. He has suffered from increasing hoarseness for six months. Laryngoscopy revealed a mass lesion over the right vocal process region without vocal paralysis. Laryngo-micro-surgery biopsy was taken, and pathology confirmed laryngeal gouty tophus without evidence of malignancy.

关键词： Gout Tophus Larynx Purine monosodium urate crystals

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