• 대한골관절종양학회지
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• 제20권2호
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• pp.85-88
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• 2014

국소형 거대 세포종은 주로 지 관절의 활액막에서 호발하는 것으로 알려져 있으며 슬관절 내에서는 드물게 발생하는 것으로 알려져 있다. 병리학적으로 다핵의 거대 세포를 특징적으로 가지는 질환으로 완전 절제 시 재발율은 낮다. 슬관절 내에 발생하는 경우 무증상에서 간헐적 잠김 증상까지 다양하게 나타날 수 있으며, 관절경적으로 완전 절제가 가능하나 불완전 절제 시 45%까지 재발하는 것으로 보고되고 있다. 저자들은 후방 십자 인대의 전연에 발생한 거대 세포종 1예를 관절경 하에서 절제 후 병리학적으로 확진하여 이를 보고하고자 한다.

• 대한한의학회지
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• 제39권4호
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• pp.86-113
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• 2018

Objectives: We examined the effects of a mixed formula consisting of dried pomegranate concentrate powder (PCP) and the aqueous extracts of Eucommiae cortex (EC) and Achyranthis radix (AR) in rats with surgically induced osteoarthritis (OA). Methods: Two weeks after OA-inducing surgery, a PCP:EC:AR 5:4:1 (g/g) combination or single formula was orally administered. Changes in body weight, knee thickness, maximum knee extension angle, bone mineral density of the knee joints, femoral and tibial articular surfaces, and compressive strength of the femoral and tibial articular cartilage (AC) were assessed, along with the prostaglandin E2 level, 5-lipoxygenase, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and chondrogenic gene mRNA expression in the femoral and tibial AC with the synovial membrane (SM). In addition, the number of cleaved poly(ADP-ribose) polymerase, cyclooxygenase and tumor necrosis factor-${\alpha}$-immunoreactive cells in the femoral and tibial AC with SM were monitored, and the rate of cell proliferation was determined with a 5-bromo-2'-deoxyuridine uptake assay. Results : The signs of surgically induced OA in rats were significantly inhibited by both PCP, EC and AR combined and single formulas. In particular, the combination formula-treated OA model rats showed dose-dependent, significantly increased inhibitory activity against all tested criteria compared with single formula-treated rats. Conclusions: Taken together, our results suggest that the combination formula synergistically increased the anti-OA effects of its components through anti-inflammatory and chondrogenic activity in rats with surgically induced OA. In addition, 200, 100 and 50 mg/kg combination formula treatments showed dose-dependent inhibitory activity against all of the tested criteria.

• IMMUNE NETWORK
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• 제22권1호
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• pp.8.1-8.20
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• 2022

Rheumatoid arthritis (RA) is a representative autoimmune disease that is primarily characterized by persistent inflammation and progressive destruction of synovial joints. RA has a complex and heterogeneous pathophysiology, involving interactions among various immune and joint stromal cells and a diverse network of cytokines and intracellular signaling pathways. With improved understanding of RA, over the past decades, therapeutic strategies have become considerably advanced and now included targeted molecular therapies, such as tumor necrosis factor inhibitors, IL-6 blockers, B-cell depletion agents, as well as inhibitors of T-cell co-stimulation and Janus kinases. However, a considerable proportion of RA patients experience refractory disease and interrupted treatment owing to the associated risk of developing serious infections and cancers. In contrast, although IL-1β, IL-17A, and p38α play significant roles in RA pathogenesis, several drugs targeting these factors have not been approved because of their low efficacy and severe adverse effects. In this review, we provide an overview of the working mechanism, advantages, and limitations of the currently available targeted drugs for RA. Additionally, we suggest potential mechanistic causes for clinically approved and failed drugs. Thus, this review provides perspectives on approaches for basic and translational studies that hold promise for identifying future next-generation therapeutics for RA.

• Journal of Microbiology and Biotechnology
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• 제33권11호
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• pp.1484-1494
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• 2023

NUC1 (Nutraceutical compound 1) is an ethanol extract composed of a formulation based on medicinal herbs traditionally used for the treatment of arthritis in Korea and China. This study investigated the therapeutic effects of NUC1 on osteoarthritis (OA). The protective effect of NUC1 on OA was tested in a rabbit model of collagenase-induced arthritis (CIA) for 4 weeks. Results were compared among four groups (n = 9 per group): the normal group (untreated), the CIA group (vehicle control), the NUC1 group (CIA rabbits treated with 200 mg/kg NUC1), and the JOINS group (positive control, CIA rabbits treated with 200 mg/kg JOINS tablet). NUC1 significantly inhibited NO production (p < 0.05 at 125 ㎍/ml, p < 0.01 at 250 ㎍/ml, and p < 0.001 at 500 ㎍/ml) and iNOS expression in macrophages, in a concentration-dependent manner. NUC1 also inhibited the release and protein expression of MMP-1, 3, and 13, in TNF-α-induced chondrosarcoma cells in a concentration-dependent manner. In vivo, the MMP-1 and MMP-3 levels in synovial fluids were significantly (p < 0.05) lower in NUC1 group (77.50 ± 20.56 and 22.50 ± 7.39 pg/ml, respectively) than in the CIA group (148.33 ± 68.58 and 77.50 ± 20.46 pg/ml, respectively). Also, in histopathological, NUC1 ameliorated articular cartilage damage in OA by increasing the abundance of chondrocytes and proteoglycan in the articular cartilage. Thus, NUC1 showed promise as a potential therapeutic agent, and it can be generalized to a broader study population in different OA animal models.

• 한방재활의학과학회지
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• 제20권4호
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• pp.33-49
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• 2010

Objectives : This study was designed to elucidate the anti-pathogenetic and curative effects of Gyehyeoldeungbokhap-bang(Jixietengfuge-fang, GCP) on Type II collagen-induced arthritis(CIA) in mice. Methods : In experiment, twenty four mices were divided into non-treated normal group(n=6), bovine type II collagen-induced control group(n=6), collagen immunized and treated two group medicated with extract of GCP(concentration of extraction: 200 mg/kg n=6, 400 mg/kg n=6) for 4 weeks after collagen immunization, Various experimental such as arthritis, incidence, index, total cell number of spleen, total cell number of peripheral lymph node(PLN), paw joint total cell number, analysis on the percentage of immunofluorescent cells of spleen in CIA induced mice, effects of inflammatory gene expression in spleen, PLN and paw joint of CIA mice, production of cytokine(IFN-${\gamma}$, IL-4, TNF-${\alpha}$, IL-6), analysis of rheumatoid factor(anti-collagen lgG, lgM level in serum) and histopathological study on the paw joint. The arthritis index, incidence were measured a week over 4 weeks after second boosting. Total cell number of spleen, peripheral lymph node, paw joint were measure after performed experiment over 7 weeks. Concentration of cytokine and rheumatoid factor in serum were measured after experiment finished. Histopathological study on the paw joint was measured after 40 days medicated with extract of GCP. Results : 1. Incidence of arthritis and index of arthritis were significantly decreased in treated group with 400 mg/kg. 2. Total cell number of spleen, PLN and paw joint were significantly decreased in treated group. 3. Analysis on the percentage of immunofluorescent cells of spleen in CIA induced mice were significantly controled compare with control group. 4. Effects of inflammatory gene expression in spleen, PLN and paw joint of CIA induced mice were significantly controled compare with control group. 5. IFN-${\gamma}$, IL-6, TNF-${\alpha}$, concentration($pg/m{\ell}$) in serum of treated group was significantly decreased compare with control group. But IL-4 was significantly increased. 6. lgM and lgG concentration($pg/m{\ell}$) in serum of treated group was significantly decreased compare with control group. 7. Histopathologically, suppurative and destructive lesion of synovial membrane, articular cartilage and subchondral bony tissue in treated group were alleviated compare with those of control group. Conclusions : Based on the results described above, it might be consider that Gyehyeoldeungbokhap-bang(Jixietengfuge-fang, GCP) has antiarthritic and analgesic effects and also inhibitory effects on the progression of collagen-induced arthritis mice.

• IMMUNE NETWORK
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• 제7권1호
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• pp.39-47
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• 2007

Background: Stromal cell-derived factor (SDF)-1 is a potent chemoattractant for activated T cells into the inflamed Rheumatoid arthritis (RA) synovium. To determine the effect of macrophage migration inhibitory factor (MIF) on the production of SDF-1 in the inflamed RA synovium. Methods: The expression of SDF-1 and MIF in RA and Osteoarthritis (OA) synovium was examined by immunohistochemical staining. The SDF-1 was quantified by RT-PCR and ELISA after RA fibroblast like synoviocyte (FLS) were treated with MIF in the presence and absence of inhibitors of intracellular signal molecules. The synovial fluid (SF) and serum levels of MIF and SDF-1 in RA, OA and healthy control were measured by ELISA. Results: Expression of SDF-1 and MIF in synovium was higher in RA patients than in OA patients. The production of SDF-1 was enhanced in RA FLS by MIF stimulation. Such effect of MIF was blocked by the inhibitors of NF-${\kappa}B$. Concentrations of SDF-1 in the serum and SF were higher in RA patients than in OA patients and healthy control. SDF-1 and MIF was overexpressed in RA FLS, and MIF could up-regulate the production of SDF-1 in RA FLS via NF-${\kappa}B$-mediated pathways. Conclusion: These results suggest that an inhibition of interaction between MIF from T cells and SDF-1 of FLS may provide a new therapeutic approach in the treatment of RA.

• Journal of Acupuncture Research
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• 제25권1호
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• pp.25-55
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• 2008

Objectives : The aim of the present study was to observe the effect of Astragali Radix Herbal-Acupuncture Solution(AR-HAS) at $ST_{36}$(jok-samni, $Z\acute{u}s\bar{a}n$ Li) on collagen- II -induced arthritis(CIA) in mice. Methods : DBA/1J mice were immunized with bovine type II collagen(CII) on days 0 and 21 to induce arthritis. The mice were divided into 5 groups : normal group(no CIA), control group(CIA+no treatment), needle prick group(CIA+single prick with an injection needle), saline group(CIA+saline injection) and ARHA group(CIA+ R-HA treatment). The needle prick, saline injection, and AR-HA groups were injected on the right $ST_{36}$(jok-samni) of mice for 9 weeks, 3 times a week, beginning 4 weeks after the booster immunization. Results : 1. The incidence of arthritis, AI(arthritis index), and joint edema decreased in the AR-HA group. 2. Weight gain, hypertrophy of the spleen, adhesion of the tissues, and transformation of the joint were restrained in the AR-HA group. 3. The concentrations of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $IFN-{\gamma}$ in CIA mouse serum and $IFN-{\gamma}$, IL-10 in the CIA mouse spleen cell culture decreased significantly at $ST_{36}$ in the AR-HA group. 4. Total cell counts increased significantly, and the ratio of $CD3e^+$ to $CD45R^+$, $CD4^+$ to $CD8^+$, and $CD4^+$ to $CD25^+$ cells decreased significantly at $ST_{36}$ in the CIA mouse spleen cell culture of the AR-HA group. 5. Total cell counts decreased significantly, and $CD4^+/CD25^+$ and $CD45R^+/CD69^+$ decreased significantly at $ST_{36}$ in the CIA mouse lymph nodes of the AR-HA group. 6. $CD3e^+/CD69^+$ and $CD11b^+/Gr-1^+$ cells decreased significantly at $ST_{36}$ in the CIA mouse joints of the AR-HA group. 7. The histological examination showed that cartilage destruction and synoviocyte proliferation decreased in the CIA mouse joints of the AR-HA group, and collagen fiber was expressed similar to that seen in the normal group. Conclusions : Our experiments show that at $ST_{36}$, an anti-inflammatory mechanism of AR-HA controls synovial cell proliferation and protects against cartilage destruction in rheumatoid arthritis.

• Journal of Acupuncture Research
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• 제24권6호
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• pp.15-27
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• 2007

Objectives : The purpose of this study is to investigate the effectiveness of Ulmus davidiana Planch herbal acupuncture(UA) to inhibit nuclear $factor(NF)-{\kappa}B$ activation on type II collagen-induced arthritis (CIA) in mice. Methods : Using an in vitro test, the synoviocytes picked out from the experimental CIA mice were subcultured. The synoviocyte cells were treated with phorbol-12-myristate-13-acetate(PMA) for 1 hour prior to the addition of indicated concentrations($0.4\;-\;1.0mg/m{\ell}$) of UA, and the cells were further incubated for 24 hours. The in vivo test, $NF-{\kappa}B$ p65, inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), vascular cell adhesion molecule(VCAM)-1 production and apoptosis was observed by immunohistochemical staining. Results : The PMA-induced $I{\kappa}B$ kinase(IKK), iNOS and COX-2 mRNA expression were dose-dependently decreased in UA treated synoviocytes. Using the in vivo test, the number of eosinophils in mice treated with UA noticeably decreased in the the CIA group(P<0.05 using student t test). In mice treated with UA, there was less cartilage erosion. less bone destruction, mild synovial hyperplasia, mild fibrosis, and mild angiogenesis with less MIP-2 production. By immunohistochemical staining, suppression of $NF-{\kappa}B$ p65, iNOS production, inhibition of COX-2 production, inhibition of VCAM-1 production and inducing apoptosis were observed. Conclusions : These results suggest that UA might be applicable to the therapy of RA to suppress $NF-{\kappa}B$ activation.

• 한국임상수의학회지
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• 제17권2호
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• pp.443-449
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• 2000

A three-year-old male jindo with generalized skin lesions (including seborrhea, hyperk- eratosis, alopecia, papules, and ecchymoses), pruritus lymph node enlargement, and fever was brought to Veterinary Teaching Hospital, College of Veterinary Medicine, Chungbuk National Uni- versity. There were no laboratory findings for parasites and fungi in the hair and skin But, the com- plete blood counts (CBC) showed leukocytosis and severe cosinophilia, It was suspected to be an inflammatory and allergic dermatitis. Thus, prednisoIone (0.5 mg/kg PO, BID for 1 week) and ampi- cillin (10 mg/kg PO, BID for 1 week given. One week later, pruritus and ecchymoses were reduced. These treatments were repeated for 7 day again. Three months later, the dog was presented again due to the relapse and exacerbation of the clinical signs. The signs were as follows; severe pru- ritus, vesicobullous skin lesions, anorexia, emaciation, lameness, and welling of carpal joints that showed inflammatory skin lesion and draining of synovia-like fluid. The values of WBC counts were returned to normal ranges. In contrast, eosinophilia was still observed. Coombs test for patient RBC and serum were negative. Hypoalbuminemia (2.5g/dl) was shown by serum chemistry. The uri- nalysis revealed and presence of leukocytes. Luxation finding of right radial carpal joint by polyarthritis was shown in radiography of affected joints.Lupus eryhematosus(LE) cells also appeared in peripheral blood and synovial fluid of affected joints. Definitely, antinuclear antibody (ANA) of patient serum using feline peripheral blood mononuclear cells was detected by all immu- nofluorescence. Based on these findings such as sedum ANA-Positive. major signs (skin disease, non- erosive polyarthritis with soft tissue swelling. and proteinuria), minor signs (fever), and LE cell-pos- itive, a diagnosis of systemic lupus crythematosus (SLE) was mad\ulcorner in this dog. The dog with SLE was administered with Pre(2.0 mg/kg PO, BID for first 4 week and then QOD) to inhibit the production of autoantibodies and with ampicillin (10 mg/kg PO, BID for first 4 weeks and then QOD) to prevent the secondary infection. The condition of this dog was monitored every 2 weeks by physical examinations, radiography, CBC, serum chemistry and urinalyais. At 8th week of treat- ment, the state of SLE evaluated by physical examinations and laboratory findings was markedly improved except for proteinura.

• 한방재활의학과학회지
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• 제24권3호
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• pp.51-69
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• 2014

Objectives This study was aimed to investigate the effects of Sibjeondaebotanggamibang (SJT) on the wound-induced rats. Methods It was observed the effects of anti-oxidation and anti-inflammation by using of lipopolysaccharide (LPS)-treated RAW 264.7 cells. For the observing on SJT anti-oxidation, it needed to mesure the total amount of polyphenol, DPPH scavenging ability, ABTS scavenging ability and the value of ROS production. In order to observe on the anti-inflammation of SJT, it was mesured the value of No and Cytokine (TNF-${\alpha}$, IL-$1{\beta}$, IL-6). It needed to make a scar (around $2{\times}2cm^2$) on the top of the fascia in the back of the rats and then the rats were divided into 4 groups (n=6). Control group was not treated at all, whereas SJ group was orally medicated SJT, Terra group was per-cutaneously applied Terramycin, and SJ+Terra group was both orally medicated SJT and percutaneously applied Terramycin per day for three weeks. The size of wound was measured with Digimatic Caliper and the blood samples (WBC, neutrophil, monocyte, lymphocyte) were analyzed using Minos-ST, which were collected by cardiac puncture. The effect on inflammatory cytokine (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), immunological cells in synovial fluid was measured. To measure the wound factor expressed by wounded skin sample, we extracted RNA and to investigate MMP-1,2,9 we used RT-PCR. For performing histopathological examinations, we paralyzed the rats by ether, and extracted wounded skin tissues, which were measured by H & E, and monitored on the optical microscope. Results 1. DPPH and ABTS scavenging activity of SJT was increased concentration-dependantly, and ROS scavenging activity was significantly increased (10, $100{\mu}g/ml$). 2. NO production was significantly reduced in SJT treated cells ($100{\mu}g/ml$), both TNF-${\alpha}$ and IL-6 in SJT treated cells (1, 10, $100{\mu}g/ml$), and IL-$1{\beta}$ in SJT treated cells (1, $100{\mu}g/ml$). 1. The size of wound was significantly decreasing in SJ group, Terra group, SJ+Terra group. 2. WBC was significantly reduced in SJ and SJ+Terra group, monocyte in SJ+Terra group. Neutrophil was also reduced in SJ, SJ+Terra group but meaningless. 3. TNF-${\alpha}$ and IL-6 were significantly reduced in SJ group, Terra group, SJ+Terra group, and IL-$1{\beta}$ in SJ+Terra group. 4. mRNA expression in MMP-1 was significantly reduced in SJ group. 5. Collegan production and chronic inflammation were significantly decreased in SJ group, Terra group, SJ+Terra groups. Re-epithelization on the skin in Terra group, SJ+Terra groups was decreased. Conclusions According to this in vitro experiment, Sibjeondaebotanggamibang (SJT) has the effects of anti-oxidative and anti-inflammatory. By in vivo experiment, SJT has the effects of anti-inflammatory. Moreover, the progress of recovery was found visually, heamatologically, genetically and histopathologically. In conclusion, it could be thought that SJT has effect on the treating of wound.