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Effects of TRPA1 activation and inhibition on TRPA1 and CGRP expression in dorsal root ganglion neurons

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Neural Regeneration Research 2019年第1期14卷 140-148页

作者： Xiao-Lei Wang Li-Wei Cui Zhen Liu Yue-Ming Gao Sheng Wang Hao Li Hu-Xiang Liu Ling-Jia Yu Department of rheumatology Qilu Hospital of Shandong University Department of Respiratory Medicine Qilu Hospital of Shandong University Department of Orthopedics Qilu Hospital of Shandong University

Transient receptor potential ankyrin 1 （TRPA1） is a key player in pain and neurogenic inflammation, and is localized in nociceptive primary sensory dorsal root ganglion （DRG） neurons. TRPA1 plays a major role in the transmission of nociceptive sensory signals. The generation of neurogenic inflammation appears to involve TRPAl-evoked release of calcitonin gene-related peptide （CGRP）. However, it remains unknown whether TRPA1 or CGRP expression is affected by TRPA 1 activation. Thus, in this study, we examined TRPA 1 and CGRP expression in DRG neurons in vitro after treatment with the TRPA1 activator tbrmaldehyde or the TRPA1 blocker menthol. In addition, we examined the role of extracellular signal-regulated protein kinase 1/2 （ERK1/2） in this process. DRG neurons in culture were exposed to formaldehyde, menthol, the ERK1/2 inhibitor PD98059 ＋ formaldehyde, or PD98059 ＋ menthol. After treatment, real-time polymerase chain reaction, western blot assay and double immunofluorescence labeling were performed to evaluate TRPA1 and CGRP expression in DRG neurons. Formaldehyde elevated mRNA and protein levels of TRPA 1 and CGRP, as well as the proportion of TRPA1- and CGRP-positive neurons. In contrast, menthol reduced TRPA1 and CGRP expression. Furthermore, the effects of lbrmaldehyde, but not menthol, on CGRP expression were blocked by pretreatment with PD98059. PD98059 pretreatment did not affect TRPA1 expression in the presence of formaldehyde or menthol.

关键词： nerve regeneration TRPA1 TRPV1 formaldehyde menthol CGRP dorsal root ganglion neuron neurogenic inflammation nociceptive signal ERK1/2 neural regeneration

Contribution of neutrophils in the pathogenesis of rheumatoid arthritis

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The Journal of Biomedical Research 2020年第2期34卷 86-93页

作者： Lingshu Zhang Yi Yuan Qiang Xu Zhengyu Jiang Cong-Qiu Chu Division of Arthritis and Rheumatic Diseases Oregon Health&Science UniversityPortlandOR 97239USA rheumatology Section VA Portland Healthcare SystemPortlandOR 97239USA Department of rheumatology and Immunology the First Hospital of Jilin UniversityChangchunJilin 130021China

Neutrophils are major innate immune effector cells for host defense and have been a topic of active research for their participation in the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis(RA)due to recently discovered neutrophil extracellular trap(NET) formation. NET formation and other mechanisms leading to the release of neutrophil nuclear and cytoplasmic contents are implicated as a source of citrullinated antigens in RA. Further investigations are required to delineate what factors diverge neutrophils from host defense to autoimmune response in RA.

关键词： neutrophils rheumatoid arthritis NET formation

Challenges in Treatment of Primary Sjogren’s Syndrome and Opportunities for Chinese Medicine

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Chinese Journal of Integrative Medicine 2020年第7期26卷 483-485页

作者： HOU Jia-qi XUE Luan Department of rheumatology and Immunology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai(200437)China

Primary Sjogren’s syndrome is a chronic autoimmune disease that can lead to systemic *** present,immunomodulatory agents have not shown good efocacy,many patients in China seek Chinese medicine *** medicine can comprehensively improve the symptoms of patients through Chinese pattern diagnosis and individualized *** researches are providing scientioc bases for the therapeutic effect of Chinese *** Chinese medicine treatment can be integrated into the conventional management of primary Sjogren’s syndrome.

关键词： primary Sjogren's syndrome immunomodulatory agents Chinese medicine

Serum Renalase Inversely Related to Heart Rate Variability in Dialysis Patients

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Journal of Shanghai Jiaotong university(Science) 2014年第4期19卷 508-512页

作者：黄宝瑞王锋李军辉汪年松 Medical College of Soochow University Department of Nephrology and rheumatology Shanghai Jiaotong University Affiliated Sixth People’s Hospital

Heart rate variability(HRV) is a noninvasive technique for autonomic nerve activity assessment and an indirect index of adrenergic cardiovascular drive. Renalase is the only known enzyme degrading circulatory catecholamines, participating in regulations of the cardiovascular and sympathetic nervous systems. This study aims at the relation between serum renalase and HRV indexes in dialysis patients. There were 14 hemodialysis(HD)cases, 16 continuous ambulatory peritoneal dialysis(PD) cases, and 16 healthy volunteers enrolled in this *** the subjects underwent 24 h Holter testing by using a dynamic electocardiogram monitor system to determine HRV parameters, and serum renalase levels were measured. The standard deviation of normal to normal R-R intervals(SDNN, a measure of beat-to-beat variability), root mean square successive difference(RMSSD), and the proportion derived by dividing NN50(the number of interval differences of successive normal to normal intervals greater than 50 ms) by the total number of NN intervals(pNN50) were determined to assess HRV. Both HD and PD patients presented increased maximum heart rate(Max-HR), minimum heart rate(Min-HR) and average heart rate(Ave-HR), and presented decreased SDNN, RMSSD and pNN50 relative to healthy controls. Serum levels of renalase were highly negatively correlated with Ave-HR(correlation coefficient r =-0.68, probability P < 0.01), while positively correlated with SDNN(r = 0.64, P < 0.01) in both the HD and PD groups. Serum level of renalase was positively correlated with 24 h urine volume(r = 0.73, P < 0.01) in PD patients. Renalase might be reciprocally related to HRV and inversely related to Ave-HR in dialysis patients, which will help to probe into renalase's physiology and may pave the way to explore renalase replacement therapy in patients with end stage renal disease(ESRD).

关键词： heart rate variability(HRV) renalase correlation heart rate(HR)

Effects of serum inflammatory factors,health index and disease activity scores on ankylosing spondylitis patients with sleep disorder

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World Journal of Psychiatry 2024年第6期14卷 866-875页

作者： Hui Wang Jia-Ying Sun Yue Zhang Department of rheumatology and Immunology The First Affiliated Hospital of Harbin Medical UniversityHarbin 150001Heilongjiang ProvinceChina

BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of *** To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep *** A total of 106 AS patients with comorbid sleep disorders were included in the *** patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical *** serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were *** activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were *** health index was obtained through the Short Form-36 *** The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep *** correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional ***,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of *** regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and *** The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep *** results emphasise the need for comprehensive care strategies that address the diverse needs and challe

关键词： Inflammatory factors Disease activity scores Health index Ankylosing spondylitis Sleep disorders

Autoantibodies targeting to GPER1 promote monocyte cytokines production and inflammation in systemic lupus erythematosus

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1354-1356页

作者： Xinwei Zhang Hongyan Qian Yangchun Chen Yuanhui Wu Yuechi Sun Yan He Shiju Chen Guixiu Shi Yuan Liu Department of rheumatology and Clinical Immunology the First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361000China Xiamen Municipal Clinical Research Center for Immune Diseases Xiamen 361000China Xiamen Key Laboratory of rheumatology and Clinical Immunology Xiamen 361000China

Dear Editor,Systemic lupus erythematosus(SLE),one of the most common autoimmune diseases in reproductive females,is a multifactorial disease involving genetic,environmental,and hormonal factors.1 It occurs at a 9:1 female-to-male ratio,and the sex predisposition suggests that the estrogen system plays an essential role in the developing of *** effects of estrogen have traditionally been attributed to the classical nuclear estrogen receptors(ERs),ERα,and ERβ,which predominantly regulate *** nucleotide-binding protein-coupled estrogen receptor 1(GPER1)is a transmembrane receptor for estrogen that mediates several rapid cellular effects of estrogen.2 Large amounts of autoantibodies characterize SLE,and anti-estrogen receptor autoantibodies are likely to affect the function of immune cells in SLE but are not yet fully understood.

关键词： antibodies lupus erythematosus

Expression of CC Chemokine Ligand 5 in Patients with Rheumatoid Arthritis and Its Correlation with Disease Activity and Medication

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Chinese Medical Sciences Journal 2009年第1期24卷 50-54页

作者： Ming-hui Yang Feng-xia Wu Chuan-mei Xie Yu-feng Qing Guang-rong Wang Xiao-lan Guo Zhong Tang Jing-guo Zhou Guo-hua Yuan Institute of rheumatology and Immunology Affiliated Hospital of North Sichuan Medical College Nanchong Sichuan 637000 China

Objective To determine the levels of CC chemokine ligand 5 (CCL5) in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and their relations with disease activity and medication. Methods CCL5 in serum and SF was quantified by enzyme-linked immunosorbent assay (ELISA) in 28 RA patients and 21 osteoarthritis (OA) patients. In RA patients, the correlations of CCL5 levels in serum and SF with disease activity were analyzed. Meanwhile, the serum CCL5 levels among RA patients treated with disease-modifying antirheumatic drugs (DMARDs), Tripterygium Glucosides, and other Chinese herbs without disease-modifying effects were also compared. Results CCL5 levels in both serum and SF of RA patients were significantly higher than those of OA patients (P<0.05). Moreover, the level of CCL5 was higher in SF than that in serum of RA patients (P<0.01). Serum CCL5 level was correlated significantly with the number of swollen joints (r=0.3329, P<0.05), erythrocyte sedimentation rate (r=0.4001, P<0.05), and C reactive protein (r=0.3735, P<0.01). In addition, the level of CCL5 had a trend of lower in patients treated with DMARDs or Tripterygium Glucosides than those treated with other Chinese herbs, although the difference was not significant among those patients due to the small number of patients in each group. Conclusions In RA patients, the expression of CCL5 increases and correlates with some clinical and laboratory parameters of RA, which indicate that CCL5 plays an important role in RA and may serve as a useful marker of disease activity. DMARDs and Tripterygium Glucosides might exert their clinical effects through reducing CCL5 production in RA.

关键词： rheumatoid arthritis chemokine CC chemokine ligand 5

Etoricoxib versus indometacin in the treatment of Chinese patients with acute gouty arthritis： a randomized double-blind trial

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Chinese Medical Journal 2013年第10期126卷 1867-1871页

作者： LI Ting CHEN Shun-le DAI Qing HAN Xing-hai LI Zhan-guo WU Dong-hai ZHANG Xiao GU Jie-ruo YANGNan-ping SUN Ling-yun ZHANG Miu-jia LI Xing-fu and BAO Chun-de Department of rheumatology Renji Hospital Shanghai JiaotongUniversity School of Medicine Shanghai 200001 China Department of rheumatology Changhai Hospital Shanghai 200438China Department of rheumatology Beijing University People's HospitalBeijing 100044 China Department of rheumatology China-Japan Friendship HospitalBeijing 100029 China Department of rheumatology Guangdong Provincial People'sHospital Guangzhou Guangdong 510120 China Department of rheumatology Third Affiliated Hospital Sun Yat-SenUniversity Guangzhou Guangdong 510630 China Department of rheumatology West China Hospitall SichuanUniversity Chengdu Sichuan 610041 China_ Department of rheumatology Nanjing Drum Tower HospitalNanjing Jiangsu 210008 China Department of rheumatology Jiangsu Province Hospital NanjingJiangsu 210029 China Department of rheumatology Qilu Hospital Jinan Shandong250012 China

Background Acute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs （NSAIDs） are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China. Methods A randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients （n=178; 〉18 years of age） with acute gouty attack （〈48 hours） were treated for 5 days with etoricoxib （120 mg/d; n=89） or indometacin （75 mg twice daily; n=89）. The primary efficacy end point was self-assessed pain in the affected joint （0-4 point Likert scale） from days 2-5. Secondary end points included investigator assessments of tenderness and swelling, patient/ investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events （AEs）. Results Etoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2-5 was 0.03 （95% confidence interval （CI） -0.19 to 0.25; P=0.6364）, which fell within the prespecifled comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most （73.7%） were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney （unrelated to etoricoxib） and fever and chills （potentially etoricoxib-related）. Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group （n=31） was less than the indometacin group （n=34）. Conclusions Etoricoxib （120 mg once daily） is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin （75 mg twice daily）.

关键词： gout, arthritis, etoricoxib, indometacin cyclooxygenase-2

Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases

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Cellular & Molecular Immunology 2021年第3期18卷 764-766页

作者： Konstantin Kotschenreuther Iris Waque Shuaifeng Yan Anja Meyer Thom Haak Julia von Tresckow Joanna Schiller Lydia Gloyer Mara Dittrich-Salamon David M.Kofler Laboratory of Molecular Immunology and Division of Clinical Immunology and rheumatology University of CologneCologneGermany DepartmentⅠof Internal Medicine University of CologneCologneGermany

The legalization of cannabinoids for medical use has reinforced their emerging role as a treatment of chronic pain in patients with cancer or rheumatic diseases.1,2 In addition to their role as pain relievers,evidence obtained from animal models suggests that cannabinoids have immunosuppressive properties.3 However,a definite immunosuppressive function of cannabinoids has not yet been confirmed in clinical trials.

关键词： rheumatic Th17 patients