• Journal of Ginseng Research
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• v.43 no.3
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• pp.335-341
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• 2019

Background: Inflammation is a host-defensive innate immune response to protect the body from pathogenic agents and danger signals induced by cellular changes. Although inflammation is a host-defense mechanism, chronic inflammation is considered a major risk factor for the development of a variety of inflammatory autoimmune diseases, such as rheumatic diseases. Rheumatic diseases are systemic inflammatory and degenerative diseases that primarily affect connective tissues and are characterized by severe chronic inflammation and degeneration of connective tissues. Ginseng and its bioactive ingredients, genocides, have been demonstrated to have antiinflammatory activity and pharmacological effects on various rheumatic diseases by inhibiting the expression and production of inflammatory mediators. Methods: Literature in this review was searched in a PubMed site of National Center for Biotechnology Information. Results: The studies reporting the preventive and therapeutic effects of ginseng and ginsenosides on the pathogenesis of rheumatic diseases were discussed and summarized. Conclusion: Ginseng and ginsenosides play an ameliorative role on rheumatic diseases, and this review provides new insights into ginseng and ginsenosides as promising agents to prevent and treat rheumatic diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.1-15
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• 2018

Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin $(IL)-1{\beta}$ and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and $Sj{\ddot{o}}gren^{\prime}s$ syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1241-1251
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• 2018

Background/Aims: To estimate the level of agreement and positivity rates of latent tuberculosis infection (LTBI) tests prior to the use of tumor necrosis factor (TNF) inhibitors in relation to underlying rheumatic diseases and endemic tuberculosis levels. Methods: The Ovid-Medline, Embase, and Cochrane Libraries were searched for articles before October 2013 involving LTBI screening in rheumatic patients, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and psoriatic arthritis. Results: In pooled analyses, 5,224 rheumatic patients had undergone both a tuberculin skin test (TST) and an interferon-gamma release assay (IGRA) before TNF inhibitors use. The positivity of TST, QuantiFERON-TB Gold In Tube (QFT-GIT), and T-SPOT.TB (T-SPOT) tests were estimated to be 29%, 17%, and 18%, respectively. The agreement percentage between the TST and QFT-GIT, and between the TST and T-SPOT were 73% and 75%. Populations from low-to-moderate endemic TB presented with slightly less agreement (71% between TST and QFT-GIT, and 74% between TST and T-SPOT) than patients from high endemic countries (73% between TST and QFT-GIT, and 81% between TST and T-SPOT). By underlying disease stratification, a lower level of agreement between TST and QFT-GIT was found among AS (64%) than among JIA (77%) and RA patients (73%). Conclusions: We reaffirm the current evidence for accuracy of LTBI test done by TST and IGRA among rheumatic patients is inconsistent. Our stratified analysis suggests different screening strategies might be needed in clinical settings considering the endemic status in the patient's country of origin and the precise nature of underlying diseases.

• The Journal of the Korean life insurance medical association
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• v.31 no.1
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• pp.19-28
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• 2012

Nowadays, Rheumatic diseases are increasing more and more. So, it's important knowing the pathophysiology and extra-risk of each rheumatic disease so as to do sound underwriting. Here is brief review and long-term prognosis of some rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sj$\ddot{o}$gren syndrome, antiphospholipid syndrome, systemic sclerosis, ankylosing spondylitis, Takayasu's arteritis, and Behcet syndrome.

• BMB Reports
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• v.52 no.6
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• pp.391-396
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• 2019

Receptor activator of nuclear factor kappa B ligand (RANKL) expression in osteoblasts is regulated by 1,25-dihydroxyvitamin D3 (1,25D3). CCAAT/enhancer-binding protein beta ($C/EBP{\beta}$) has been proposed to function as a transcription factor and upregulate RANKL expression, but it is still uncertain how $C/EBP{\beta}$ is involved in 1,25D3-induced RANKL expression of osteoblasts. 1,25D3 stimulation increased the expression of RANKL and $C/EBP{\beta}$ genes in osteoblasts and enhanced phosphorylation and stability of these proteins. Moreover, induction of RANKL expression by 1,25D3 in osteoblasts was downregulated upon knockdown of $C/EBP{\beta}$. In contrast, $C/EBP{\beta}$ overexpression directly upregulated RANKL promoter activity and exhibited a synergistic effect on 1,25D3-induced RANKL expression. In particular, 1,25D3 treatment of osteoblasts increased $C/EBP{\beta}$ protein binding to the RANKL promoter. In conclusion, $C/EBP{\beta}$ is required for induction of RANKL by 1,25D3.

• 대한근관절건강학회:학술대회논문집
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• 1998.04a
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• pp.123-131
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• 1998

• IMMUNE NETWORK
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• v.7 no.3
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• pp.124-132
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• 2007

Background: Regulatory T cells (Tregs) have been investigated intensively for some decades. These cells regulate the immune system, prevent overactivated immune responses and can be used therapeutically. For rheumatoid arthritis (RA), understanding the functions and status of Tregs is an important step for understanding immune regulation in this autoimmune disease. Methods: We investigated the percentages, phenotypes and suppressive functions of $CD4^+CD25^+$ Tregs in peripheral blood (PB) of patients with RA. Results: The percentages were higher in the patients (n=12) than in healthy controls (n=10), and the cells expressed the $CD45RB^{low}$, CTLA-4 and CCR7 phenotypes. We also investigated the expression of Foxp3 and secretion of interleukin (IL)-10 induced $CD4^+CD25^+$ Tcells by anti-CD3 antibody treatment. A suppressive function of the patients' cells was shown through coculture with $CD4^+CD25^-$ T cells in vitro. Conclusion: We suggest that, despite their increased numbers and suppressive function, they manage the ongoing inflammation ineffectively. It might be possible to apply IL-10 to induce the proliferation of IL-10-producing Tregs as therapy for RA.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.144-148
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• 2018

Background: Panax ginseng is a well-known immune modulator, and there is concern that its immune-enhancing effects may negatively affect patients with rheumatoid arthritis (RA) by worsening symptoms or increasing the risk of adverse effects from other drugs. In this randomized, crossover clinical trial, we evaluated the impact of Korean Red Ginseng (KRG) on disease activity and safety in RA patients. Methods: A total of 80 female RA patients were randomly assigned to either the KRG (2 g/d, n = 40) treatment or placebo (n = 40) groups for 8 wk, followed by crossover to the other treatment group for an additional 8 wk. The primary outcome was the disease flare rate, defined as worsening disease activity according to the disease activity score 28 joints-erythrocyte sedimentation rate (DAS28-ESR). The secondary outcomes were development of adverse events (AEs) and patient reported outcomes. Outcomes were evaluated at baseline and 8 wk and 16 wk. The outcomes were compared using the Chi-square test. Results: Of the 80 patients, 70 completed the full study. Their mean age was 51.9 yr, and most exhibited low disease activity (mean DAS28-ESR $3.5{\pm}1.0$) at enrollment. After intervention, the flare rate was 3.7% in each group. During KRG treatment, 10 AEs were reported, while five AEs were developed with placebo; however, this difference was not statistically significant (p = 0.16). Gastrointestinal- and nervous system-related symptoms were frequent in the KRG group. Conclusion: KRG is not significantly associated with either disease flare rate or the rate of AE development in RA patients.

• Journal of muscle and joint health
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• v.7 no.1
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• pp.131-147
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• 2000

Almost all patients with rheumatic disease experience fatigue. The fatigue affects the patient's life extensively at home and at work, therefore it is necessary to investigate the nature of the fatigue which the patients perceive. The purpose of this study is to explore the nature and pattern of fatigue of the patients with rheumatic diseases. Rheumatoid arthritis is typical disease for its joint involvement which leads to deformity. Whereas lupus is a characteristic systemic autoimmune disease and the fibromyalgia is characterized by the general bodyache and multiple local tenderness. The prevalence of these diseases and the fatigue was known to be higher in women than men. Therefore the subjects were woman patient diagnosed as rheumatoid arthritis, lupus or fibromyalgia, and they were recruited from the H-Rheumatic Disease Hospital. The two instruments, the Multidimensional Assessment of Fatigue by Belza(1995) and the Piper Fatigue Scale by Piper, et al(1995) were used to explore the nature and pattern of self-reported fatigue. In total, the data from 157 patients were analysed by the SPSS-PC program for statistical analysis. The results were as follows: 1. Most patients with rheumatic disease experienced fatigue and the degree of fatigue was at the middle range by the scores of the two instruments. 2. The degree of fatigue of the patients with fibromyalgia was the highest and the next was that of the patients with lupus and the fatigue of the patients with rheumatoid arthritis. But there were no statistically significant differences among the patients with three rheumatic diseases, except the subcategory, the meaning of fatigue of the Piper Fatigue Scale. 3. Even when the period of the symptom and pain were covariated, there were no statistically significant differences among patients with three rheumatic diseases. The fatigue of the patients with lupus and fibromyalgia is rarely investigated in Korea and this study can be the base for the further understanding of the patients with rheumatic diseases. Therefore repeated studies are required to identify the factors to affect the fatigue and to understanding the nature of the diseases and to develop the nursing interventions to alleviate the fatigue.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.201-210
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• 2003

Objective: The role of prostaglandin $E_2$ (PGE2) in the etiopathogenesis of immune and inflammatory diseases has become the subject of recent debate. To determine the role of PGE2 in rheumatoid arthritis (RA), we tested the effect of exogenous PGE2 on the production of cyclooxygenase-2 (COX-2) by rheumatoid synoviocytes. Methods: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of PGE2. The COX-2 mRNA and protein expression levels were determined by RT-PCR and Western blot analysis, respectively. The PGE2 receptor subtypes in the FLS were analyzed by RT-PCR. Electrophoretic mobility shift assay (EMSA) was used to measure the NF-${\kappa}B$ binding activity for COX-2 transcription. The in vivoeffect of PGE2 on the development of arthritis was also tested in collagen induced arthritis (CIA) animals. Results: PGE2 ($10^{-11}$ to $10^{-5}M$) dose-dependently inhibited the expression of COX-2 mRNA and the COX-2 protein stimulated with IL-$1{\beta}$, but not COX-1 mRNA. NS-398, a selective COX-2 inhibitor, displayed an additive effect on PGE2-induced COX-2 downregulation. The FLS predominantly expressed the PGE2 receptor (EP) 2 and EP4, which mediated the COX-2 suppression by PGE2. Treatment with anti-IL-10 monoclonal antibodies partially reversed the PGE2-induced suppression of COX-2 mRNA, suggesting that IL-10 may be involved in modulating COX-2 by PGE2. Experiments using an inducer and an inhibitor of cyclic AMP (cAMP) suggest that cAMP is the major intracellular signal that mediates the regulatory effect of PGE2 on COX-2 expression. EMSA revealed that PGE2 inhibited the binding of NF-${\kappa}B$ in the COX-2 promoter via a cAMP dependent pathway. In addition, a subcutaneous injection of PGE2 twice daily for 2 weeks significantly reduced the incidence and severity of CIA as well as the production of IgG antibodies to type II collagen. Conclusion: Our data suggest that overproduced PGE2 in the RA joints may function as an autocrine regulator of its own synthesis by inhibiting COX-2 production and may, in part, play an anti-inflammatory role in the arthritic joints.