• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.117-117
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• 2003

Bee Venom (BV) has been treated in inflammatory diseases such as rheumatoid arthritis (RA). Bee venom contains several biologically active non-peptide substances as well as two major known peptides; the hemolytic peptide melittin (50%) and the neurotoxic peptide apamin, and a number of minor peptides.(omitted)

• IMMUNE NETWORK
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• 제7권1호
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• 대한한의학회지
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• 제31권4호
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• pp.63-78
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• 2010

Objectives: This study was carried out to know the effects of Gwan-Jul-Bang-7 (hereafter referred to GJB-7) on the inhibition of arthritis induced by collagen on the mouse. Methods: To assess the effects of GJB-7 on mouse with arthritis induced by collagen II, we conducted several experiments such as analysis of cytotoxicity, hepatotoxicity, arthritis index, total cell number of draining lymph nodes and paw joints, value of immunocyte in PBMC (peripheral blood mononuclear cell), DLN (draining lymph node) and paw joint, measurement of cytokine and anti-collagen II, observation of the histological changes of joint. Results: 1. Cytotoxicity against HFC (human fibroblast cells) was not observed in any concentration and hepatotoxicity was not observed in the GJB-7 treated group. 2. The incidence of arthritis significantly decreased. 3. Total cell number of draining lymph nodes significantly increased and total cell number of paw joints significantly decreased. 4. The percentage of $CD8^+$ cells in PBMC (peripheral blood mononuclear cell) significantly increased. The percentage of $CD3^+/CD69^+$, and $CD3^+/CD49b^+$ cells in PBMC significantly decreased. 5. The percentage of $CD19^+,\;CD3^+$, and $CD4^+/CD25^+$ cells in DLN (draining lymph nodes) significantly increased. The percentage of $B220^+/CD23^+$ cells in DLN significantly decreased. 6. The percentage of $CD3^+,\;CD4^+$, and $CD11b^+/Gr-1^+$ cells in paw joints significantly decreased. 7. The production of TNF-$\alpha$, IL-6, and MCP-1 significantly decreased. 8. Anti-collagen II in serum significantly decreased. 9. With the hematoxylin and eosin stain, inflammation of joint decreased. Under Masson's trichrome stain, the cartilage destruction and synovial cell proliferation and the expression of collagen fibers decreased. Conclusions: Comparison of the results for this study showed that GJB-7 had immunomodulatory effects. So we expect that GJB-7 could be used as an effective drug for not only rheumatoid arthritis but also another auto-immune diseases.

• International Journal of Advanced Culture Technology
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• 제7권4호
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• pp.156-162
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• 2019

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by progressive joint deterioration; Furthermore, RA can also affect body tissues, including the skin, eyes, lungs, heart and blood vessels. The early stages of RA can be difficult to diagnose because the signs and symptoms mimic those of many other diseases. It is not known exactly what triggers the onset of RA and how to cure the disease. But recent discoveries indicate that remission of symptoms is more likely when treatment begins early with strong medications known as disease-modifying anti-rheumatic drugs (DMARDs). Tumor necrosis factor (TNF) inhibitors are typical examples of biotherapies that have been developed for RA. The substances may occur naturally in the body or may be made in the laboratory. Other biological therapies care biological response modifiers (BRMs)such as monoclonal antibodies, interferon, interleukin-2 (IL-2) and a protein binder using repeat units. These substances play significant anti-inflammatory roles. Proteins with recurrent, conserved amino acid stretches mediate interactions among proteins for essential biological functions; for example, ankyrin (ANK), Heat repeat protein (HEAT), armadillo repeat protein (ARM) and tetratricopeptide repeats (TPR). Here, we describe Leucine rich repeats (LRR) that ideally fold together to form a solenoid protein domain and is more applicable to our current study than the previously mentioned examples. Although BRMs have limitations in terms of immunogenicity and effector functions, among other factors, in the context therapeutic use and for proteomics research, We has become clear that repeat-unit-derived binding proteins will increasingly be used in biotechnology and medicine.

• Korean Journal of Acupuncture
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• 제24권3호
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• pp.117-137
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Gentianae macrophyllase Radix herbal-acupuncture solution(GR-HAS) at Joksamni(ST36) on Collagen-induced arthritis(CIA) in DBA/1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen II , change of immunocyte count, histological change of CIA mouse joint related with RA. Results : 1. In the GR-HA group, the arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In GR-HA group, there were no weight loss and similarly maintained as normal group. Spleen size, adhesion rate and the edema and transformation of knee joint were low and similarly maintained as normal group. 3. In the GR-HA, cytokine level, IgG, IgM and anti-collagen II were significantly decreased. 4. In the GR-HA, the change of immunocyte count were similarly maintained as normal group. 5. In the histological changes of the CIA mouse joint, the cartilage destruction and synovial cell proliferation were decreased in the GR-HA(Hematoxylin and eosin stain). The collagen fiber expressions in the GR-HA were similar with that of the normal group(Masson's Trichrome stain) Conclusions : These results suggest that GR-HA at ST36 has an effect to control immune reaction and suppress inflammation, synovial cell proliferation and cartilage destruction in rheumatoid arthritis.

• 대한한방부인과학회지
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• 제22권2호
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• pp.1-25
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• 2009

Purpose: The purpose of this study is to investigate the anti-arthritis effects of Jeonsaenghwalhyeoltanggamibang(JHTG) on collagen-induced arthritis(CIA) in mice. Methods: To assess the effects of JHTG on CIA in mice, we conducted several experiments such as analysis of arthritis index, cell count of draining lymph node(DLN) and paw joint, measurement of serum antibody levels and observation of the histological changes of joint. Results: 1. JHTG extract had a suppressive effect on the arthritis index of paw joints in CIA mice. 2. JHTG extract increased the total cell number of DLN, and decreased the total cell number of paw joints in CIA mice. 3. JHTG extract increased the absolute number of various cell surface receptors in DLN, and decreased the absolute number of B220+/CD23+ cells in DLN in CIA mice. 4. JHTG extract decreased the absolute number of CD3+, CD4+, CD11b+/Gr-1 cells in paw joint in CIA mice. 5. JHTG extract didn't decrease the absolute number of CD4+/CD25+ cells in paw joints in CIA mice. 6. JHTG extract decreased levels of total IgM in the serum of CIA mice, but had no effect on levels of collagen II specific antibody. 7. JHTG extract decreased the destruction of articular cartilages and collagen fibers and the proliferation of synovial cells in paw joints from CIA mice. Conclusion: These results indicate that JHTG has clinical potential for the treatment of rheumatoid arthritis by modulating the immune response.

• 대한약침학회지
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• 제22권4호
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• pp.210-224
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• 2019

Rheumatoid arthritis is a severe autoimmune disorder, related to joints. It is associated with serious cartilage destruction. This causes disability and reduces the excellence of life. Numerous treatments are existed to combat this disease, however, they are not very efficient and possess severe side effects, higher doses, and frequent administration. Therefore, newer therapies are developed to overcome all these limitations. These include different monoclonal antibodies, immunoglobulins, small molecules used for immunotherapy and transgenes for gene therapy. One of the main goals of these new generation therapeutics is to address the underlying distressing biological processes by specifically targeting the causative agents with fewer systemic side effects and greater patient console. It is very fortuitous that loads of progressive investigations are going on in this field and many of them have entered into the successful clinical trial. But till date, a limited molecule has got FDA clearance and entered the market for treating this devastating disease. This review highlights the overview of conventional therapy and advancements in newer therapeutics including immunotherapy and gene therapy for rheumatoid arthritis. Further, different novel techniques for the delivery of these therapeutics of active and passive targeting are also described.

• 동의생리병리학회지
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• 제19권6호
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• pp.1647-1655
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• 2005

Gamimahaenggamsuk-tang (GMHGST) is used for treatment of inflammatory diseases including rheumatoid arthritis (RA). Here, regulatory activity of GMHGST on RA-mediated inflammatory responses was investigated in cultured human fiDroblast-like synoviocytes (FLS), Levels of mRNAs encoding for inflammatory cytokines such as $IL-1{\beta}$, IL-6 and IL-8 and NOS-II enzyme, which had been induced by $TNF-{\alpha}$ and $IL-1{\beta}$ cotreatment, were decreased to the similar levels as those in cells treated with anti-inflammatory agent MTX. mRNA expressions of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases (TIMPs) as well as intercellular adhesion molecule (ICAM) were also downregulated by increasing doses of GMHGST in activated FLS. Moreover, GMHGST appeared to protect cells by decreasing NO levels, and inhibited cell proliferation which had been induced by inflammatory stimulation by $TNF-{\alpha}$ and IL-1. These results suggest that GMHGST is effective as an inhibitory agent for regulating inflammatory responses in activated FLS.

• 한국건강관리협회지
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• 제2권2호
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• pp.154-159
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• 2004

Rheumatoid arthritis(RA) is the most common inflammatory joint disease and a major cause of disability, morbidity, and mortality. It occurs worldwide, affecting approximately one percent of adults. Inflammation of the synovial membrane surrounding a joint leads to swollen, tender, and stiff joints RA has no known cure and the diagnosis is made based on clinical criteria and many different options exist for treatment. All of these factors magnify the importance of the patient-physician interaction and place a premium on the art rather than the science of medicine. The major goals of therapy for RA are to relive pain, swelling, and fatigue; improve joint function; stop joint daage, and prevent disability and disease-related morbidity. Some combination of nonsteroidal anti-inflammatory drugs(NSAIDs), steroids, and DMARDs is necessary in almost patients. In many combinations of different DMARDs or DMARDs plus biologicals are necessary for optimal control. Additionaly, all patients with RA should be educated about their disease and the therapies that will be used. Patient education is essentially early in the disease course and on going basis Much research is focused on the further development of biological agent for treatment of RA. Elucidation of the trigger or trigers for RA may allow us to begin to think about prevention of RA.

• IMMUNE NETWORK
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• 제19권1호
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• pp.2.1-2.13
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• 2019

The enhanced differentiation and activation of osteoclasts (OCs) in the inflammatory arthritis such as rheumatoid arthritis (RA) and gout causes not only local bone erosion, but also systemic osteoporosis, leading to functional disabilities and morbidity. The induction and amplification of NFATc1, a master regulator of OC differentiation, is mainly regulated by receptor activator of NF-κB (RANK) ligand-RANK and calcium signaling which are amplified in the inflammatory milieu, as well as by inflammatory cytokines such as TNFα, IL-1β and IL-6. Moreover, the predominance of CD4⁺ T cell subsets, which varies depending on the condition of inflammatory diseases, can determine the fate of OC differentiation. Anti-citrullinated peptide antibodies which are critical in the pathogenesis of RA can bind to the citrullinated vimentin on the surface of OC precursors, and in turn promote OC differentiation and function via IL-8. In addition to adaptive immunity, the activation of innate immune system including the nucleotide oligomerization domain leucine rich repeat with a pyrin domain 3 inflammasome and TLRs can regulate OC maturation. The emerging perspectives about the diverse and close interactions between the immune cells and OCs in inflammatory milieu can have a significant impact on the future direction of drug development.