Influence of moxibustion at “Shènshù” ( BL 23) and “Zúsānl□” ( ST 36) on Ras-MAPK signal pathways in synovial tissues of rats with experimental rheumatoid arthritis

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

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THU0206 А VERY EARLY (7-28 DAYS) RESPONSE ON JAK INHIBITOR TOFACITINIB IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: EFFECT ON PAIN AND CENTRAL SENSITIZATION.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4029 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 327.3-327

Author(s):

A. Karateev ◽

E. Filatova ◽

E. Pogozheva ◽

V. Amirdzhanova ◽

E. Nasonov ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Central Sensitization ◽

Early Time ◽

National Registry ◽

Genetically Engineered ◽

Pain Severity ◽

Signal Pathways ◽

Jak Inhibitor ◽

Jak Inhibitors ◽

Biological Drugs

Background:The presence of central sensitization (CS) significantly burdens the course of rheumatoid arthritis (RA). JAK inhibitors block intracellular signal pathways including the ones responsible for synthesis of mediators and cytokines causing pain and CS. The application of JAK inhibitors is supposed to relieve pain and reduce CS severity promptly.Objectives:To evaluate JAK inhibitor effect on pain and signs of CS in patients with active RA 7 and 28 days after the start of therapy.Methods:Study group included 39 patients with RA, their age was 50.9±11.1, 79.5% of women, 89.7% of RF “+”, DAS28 5.8±0.6, receiving DMARDs (methotrexate 82.0% and leflunomide 18.0%), who were administered with tofacitinib 5 mg 2 times a day due to inefficiency or intolerance of genetically engineered biological drugs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration.Results:Patients initially experienced a severe pain – 5.72±2.21 according to the visual analogue scale (VAS), 53.8% had signs of central sensitization (CSI ≥ 40), 17.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.37±2.2 (р=0.01), pain decrease of 29.4±17.9% (BPI), NCP – PainDETECT from 12.9±5.5 to 10.6±5.6 (р=0.047) and CS – CSI from 43.1±12.8 to 35.9±11.2 (р=0.01). The effect had increased after 28 days: pain level (VAS) was 2.84±1.57 (р=0.000), pain decrease of 43.6±29.6% (BPI), PainDETECT 29.8±12.4 (р=0.000), CSI 26.4±13.9 (р=0.000).During this period there were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect, also due to impact on CS and NCP.Source: National Registry patients with RADisclosure of Interests: :Andrey Karateev: None declared, Ekaterina Filatova: None declared, Elena Pogozheva: None declared, Vera Amirdzhanova: None declared, Evgeny Nasonov: None declared, Alexander Lila: None declared, V Mazurov: None declared, N Lapkina: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Tatiana Salnikova: None declared, Ruzana Samigullina: None declared, Diana Chakieva: None declared, Irina Marusenko: None declared, Olga Semagina: None declared, Marina Semchenkova: None declared

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Association ofEMCNwith Susceptibility to Rheumatoid Arthritis in a Japanese Population

The Journal of Rheumatology ◽

10.3899/jrheum.100263 ◽

2010 ◽

Vol 38 (2) ◽

pp. 221-228 ◽

Cited By ~ 5

Author(s):

KAZUMASA NISHIMOTO ◽

KATSUNORI IKARI ◽

HIROTAKA KANEKO ◽

SO TSUKAHARA ◽

YUTA KOCHI ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Association Studies ◽

Functional Study ◽

Positive Staining ◽

Nucleotide Polymorphisms ◽

Data Set ◽

Nuclear Factors ◽

Validation Set ◽

Synovial Tissues ◽

Stratified Analysis

Objective.Endomucin, an endothelial-specific sialomucin, is thought to facilitate “lymphocyte homing” to synovial tissues, resulting in the major histopathologies of rheumatoid arthritis (RA). We examined the association between RA susceptibility and the gene coding endomucin,EMCN.Methods.Association studies were conducted with 2 DNA sample sets (initial set of 1504 patients, 752 controls; and validation set, 1113 patients, 940 controls) using 6 tag single-nucleotide polymorphisms (SNP) from the Japanese HapMap database. Immunohistochemistry for the expression of endomucin was conducted with synovial tissues from 4 patients with RA during total knee arthroplasty. Electromobility shift assays were performed for the functional study of identified polymorphisms.Results.Within the initial sample set, the strongest evidence of an association with RA susceptibility was SNP rs3775369 (OR 1.20, p = 0.0075). While the subsequent replication study did not initially confirm the observed significant association (OR 1.13, p = 0.062), an in-depth stratified analysis revealed significant association in patients testing positive to anti-cyclic citrullinated peptide (anti-CCP) antibody in the replication data set (OR 1.15, p = 0.044). Investigating 2 sample sets, significant associations were detected in overall and stratified samples with anti-CCP antibody status (OR 1.17, p = 0.0015). Positive staining for endomucin was detected in all patients. The allele associated with RA susceptibility had a higher binding affinity for HEK298-derived nuclear factors compared to the nonsusceptible allelic variant of rs3775369.Conclusion.A significant association betweenEMCNand RA susceptibility was detected in our Japanese study population. TheEMCNallele conferring RA susceptibility may also contribute to the pathogenesis of RA.

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Effect of electroacupuncture on JAK2/STAT3 pathway in synovial tissues of rats with rheumatoid arthritis

Journal of Acupuncture and Tuina Science ◽

10.1007/s11726-019-1121-z ◽

2019 ◽

Vol 17 (4) ◽

pp. 223-230

Author(s):

Wei-min Fan ◽

Chun-jiang Zhao

Keyword(s):

Rheumatoid Arthritis ◽

Stat3 Pathway ◽

Synovial Tissues

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Effect of Human Herpesviruses 6 and 7 Infection on the Clinical Course of Rheumatoid Arthritis / Cilvēka Herpesvīrusa 6 Un 7 Infekcijas Ietekme Uz Reimatoīdā Artrīta Klīnisko Gaitu

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.1515/prolas-2016-0028 ◽

2016 ◽

Vol 70 (4) ◽

pp. 165-174 ◽

Cited By ~ 2

Author(s):

Anda Kadiša ◽

Zaiga Nora-Krūkle ◽

Svetlana Kozireva ◽

Simons Svirskis ◽

Pēteris Studers ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Viral Infections ◽

Clinical Course ◽

Immunosuppressive Treatment ◽

Virus Reactivation ◽

Autoimmune Inflammatory Disease ◽

High Prevalence ◽

Synovial Tissues ◽

Infection Markers

Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and -7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.

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The role of meat in the expression of rheumatoid arthritis

British Journal Of Nutrition ◽

10.1017/s0007114500001926 ◽

2000 ◽

Vol 84 (5) ◽

pp. 589-595 ◽

Cited By ~ 43

Author(s):

William B. Grant

Keyword(s):

Rheumatoid Arthritis ◽

Short Review ◽

Ecological Approach ◽

Statistical Association ◽

Prevalence Data ◽

Statistical Correlations ◽

Period 2 ◽

Dietary Components ◽

Synovial Tissues

Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r2 0·877, P<0·001 for eight countries). The statistical correlations for meat and offal were almost as high as those for their fat. Similar correlations were found for temporal changes in indices of effects of RA in several European countries between 1968 and 1978 as more meat was added to the national diets, although the correlations were higher for meat than for fat. It is hypothesized that meat and offal may be a major factor contributing to the inflammation in RA. In the present short review, the author examines some of the data that associate meat consumption with RA and the possible factors, e.g. fat, Fe and nitrite, which may contribute to the inflammation.

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Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

Biomolecules ◽

10.3390/biom9120795 ◽

2019 ◽

Vol 9 (12) ◽

pp. 795 ◽

Cited By ~ 12

Author(s):

Qing Zhang ◽

Jia Liu ◽

Mengmeng Zhang ◽

Shujun Wei ◽

Ruolan Li ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Mechanisms ◽

Herbal Medicines ◽

Janus Kinase ◽

Mitogen Activated Protein Kinase ◽

Signal Pathways ◽

Apoptosis Induction ◽

Apoptotic Pathway ◽

Induction Of Apoptosis ◽

Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

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