• IMMUNE NETWORK
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• v.21 no.6
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• pp.45.1-45.13
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• 2021

Many mouse models of rheumatoid arthritis have been identified, but only a limited number are present for axial spondyloarthritis (AxSpA). Collagen Ab-induced arthritis (CAIA) is one of the most widely used mouse models of arthritis, and it is complement-dependent. We found that mice developing CAIA also developed spinal lesions similar to those found in AxSpA. To induce CAIA, mice were injected intraperitoneally at day 0 with anti-collagen Abs, followed by LPS injection at day 3. CAIA mice demonstrated a significant kyphosis through the spine, as well as hypertrophic cartilage and osseous damage of the intravertebral joints. Immunohistochemical staining of the kyphotic area revealed increased complement C3 deposition and macrophage infiltration, with localization to the intravertebral joint margins. Near Infrared (NIR) in vivo imaging showed that anti-collagen Abs conjugated with IRDye^® 800CW not only localized to cartilage surface in the joints but also to the spine in arthritic mice. We report here a novel preclinical mouse model in which, associated with the induction of CAIA, mice also exhibited salient features of AxSpA; this new experimental model of AxSpA may allow investigators to shed light on the local causal mechanisms of AxSpA bone and soft tissue changes as well as treatment.

• Korean Journal of Veterinary Research
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• v.46 no.4
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• pp.305-313
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• 2006

The primary goal of the wound healing is rapid wound closure. Recent advances in cellular and molecular biology have greatly expanded our understanding of the biologic processes involved in wound repair and tissue regeneration. This study was conducted to develop a new sponge type of biomaterial to be used for either wound dressing or scaffold for tissue engineering. We designed to make a comparative study of the wound healing effect of silk fibroin/hyaluronic acid (SF/HA) blend sponge in full-thickness dermal injury model of rat. Two full-thickness excisions were made on the back of the experimental animals. The excised wound was covered with either the silk fibroin (SF), hyaluronic acid (HA) or SF/HA (7 : 3 or 5 : 5 ratio) blend sponge. On the postoperative days of 3, 7, 10 and 14, the wound area was calculated by image analysis software. Simultaneously, the tissues were stained with Hematoxylin-Eosin and Masson's trichrome methods to measure the area of regenerated epithelium and collagen deposition. In addition, we evaluated the degree of the epithelial cell proliferation using immunohistochemistry for proliferating cell nuclear antigen (PCNA). We found that the half healing time ($HT_{50}$) of SF/HA blend sponge treated groups were significantly decreased as compared with either those of SF or HA treatment group. Furthermore, SF/HA blend sponges significantly increased the size of epithelialization and collagen deposition as well as the number of PCNA positive cells on epidermal basement membrane as compared with those of control treatment. Especially, the 5 : 5 ratio group of SF/HA among all treatment groups was most effective on wound healing rate and histological studies. These results suggest that SF/HA blend sponges could accelerate the wound healing process through the increase of epithelialization, collagen deposition and basal cell proliferation in full thickness skin injury.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.871-886
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• 2008

Objective : Gypsum fibrosum has been traditionally used in treatment of febrile diseases and recently been shown to have anti-inflammatory effect. Chronic renal failure has a serious clinical symptoms including proteinuria, azotemia, anemia, and hyperlipidemia and has characteristic histopathological changes, glomerular hypertrophy, infiltration of inflammatory cells, and crescentic sclerosis, We investigated the effects of gypsum fibrosum on renal functional and histopathological disorder in chronic renal failure rat model induced 5/6 nephrectomy. Methods : Using Sprague-Dawley rats, CRF was induced by 5/6 nephrectomy. The rats were divided into 3 groups, normal, conrol, and gypsum administered orally with gypsum fibrosum 500mg/kg/day. Body weight, 24 hr proteinuria, hematologic analysis, and histological morphologic changes were followed up after 8 weeks. The glomerular macrophage/monocyte infiltration, $TGF-{\beta}_1$, type IV collagen, and angiotensin II type1 receptor($AT_1$) were evaluated by immunohistochemistry. Resuls : In the CRF control group, functional parameters and histopathologic changes clearly indicated the development of CRF. 24 hr proteinuria significantly increased in the CRF control group over the normal group, and serum creatinine level was lower in the gypsum group than in the control group, LDL-cholesterol was significantly lower in the gypsum group than in the control group. Morphological investigations showed a variety of characteristic features of CRF, glomerular hypertrophy, increasing cellular density of glomerulus, deposition of extra-cellular matrix, fibrotic change, and glomerular sclerosis in the control group, but in the gypsum group, these features diminished significantly. In observation of renal type IV collagen and $AT_1$ expression, positive area significantly increased in the control group over the normal group, and it significantly decreased in the gypsum group compared to the control group. Conclusions : Our findings suggest that gypsum fibrosum inhibits $AT_1$ and type IV collagen expression in renal tissues and attenuates progression of glomerulosclerosis and interstitial fibrosis in chronic renal failure rats, which lead to amelioration of renal function. From these results, we suggest that gypsum fibrosum may have renoprotective effects and could be a useful remedy agent for treating chronic renal failure.

• The Journal of Korean Physical Therapy
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• v.27 no.3
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• pp.140-146
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• 2015

Purpose: To determine the effects of 630 nm light emitting diode (LED) on full-thickness wound healing. Methods: Twelve male Sprague-Dawley rats were randomly divided into LED (n=6) and control group (n=6). Two $19.63mm^2$ wounds were created on the mid dorsum. LED group received a 630 nm LED irradiation with $3.67mW/cm^2$ for 30 minutes ($6.60J/cm^2$) for 7 days, while control group received sham LED irradiation. Epithelial gap, collagen density, ${\alpha}$-SMA fibroblast and PCNA keratinocyte were measured on histochemical and immunohistochemical staining using image analysis system. An independent t-test was conducted to compare the difference between groups. Results: The wound closure rate, collagen density, ${\alpha}$-SMA fibroblast number, epithelial gap and PCNA keratinocyte number have shown no significant difference between LED and control group at day 3 after the treatment. At day 7 after the treatment, the wound closure rate in LED group was increased when compared with control group (p<0.05). The collagen density (p<0.05) and ${\alpha}$-SMA immunoreactive fibroblast number (p<0.001) were increased when compared with control group at day 7. The epithelial gap in LED group was significantly shorten than control group at day 7 (p<0.01). The PCNA positive cell number in LED group was higher than control group at day 7 (p<0.01). Conclusion: 630 nm LED with $3.67mW/cm^2$, $6.60J/cm^2$ accelerate collagen deposition by stimulating fibroblasts, and enhance wound contraction by differentiating myofibroblasts in the dermis, and accelerate keratinocyte proliferation by facilitating DNA synthesis in the epidermis. It may promote the healing process in proliferation stage of wound healing.

• Preventive Nutrition and Food Science
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• v.19 no.3
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• pp.194-203
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• 2014

Yam (Dioscorea batatas) is widely consumed as functional food for health promotion mainly in East Asia countries. We assessed whether yam root (tuber) or bark (peel) extracts stimulated the activity of osteoblasts for osteogenesis. MC3T3-E1 cells (mouse osteoblasts) were treated with yam root extracts (water or methanol) (study I) or bark extracts (water or hexane) (study II) within $0{\sim}10{\mu}g/mL$ during the periods of osteoblast proliferation (5~10 day), matrix maturation (11~15 day) and mineralization (16~20 day) as appropriate. In study I, both yam root water and methanol extracts increased cell proliferation as concentration-dependent manner. Cellular collagen synthesis and alkaline phosphatase (ALP) activity, both the indicators of bone matrix protein and inorganic phosphate production for calcification respectively, were also increased by yam root water and methanol extract. Osteoblast calcification as cell matrix Ca and P accumulation was also increased by the addition of yam root extracts. In study II, yam bark extracts (water and hexane) increased osteoblast proliferation and differentiation, as collagen synthesis and ALP activity and osteoblast matrix Ca and P deposition. The study results suggested that both yam root and bark extracts stimulate osteogenic function in osteoblasts by stimulating bone matrix maturation by increasing collagen synthesis, ALP activity, and matrix mineralization.

• Journal of Animal Reproduction and Biotechnology
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• v.34 no.1
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• pp.20-29
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• 2019

Soy isoflavones have been reported to possess many physiological activities such as antioxidant activity and inhibition of cancer cell proliferation. This study investigated the photoprotective effects of soybean extract in human fibroblast cell line and hairless mice model. Human fibroblast was treated with soybean extract before and after ultraviolet B (UVB; 290-302 nm) irradiation. In the soybean extract treated group, the cells showed better resistance to ultraviolet (UV) than control group. The amount of type I collagen recovered from the soybean treated group was higher than the vehicle group exposed to UV-induced damage. Moreover, increased expression of metalloproteinases-1 as a result of UV irradiation was suppressed by the soybean extract. Female mice were orally administered soybean extract and irradiated with UVB light for 8 weeks. The effects of the soybean extract on the skin appearance, collagen deposition and epidermal thickness in the UV-damaged mouse skin were analyzed using histopathological methods. In soybean extract treated group, the skin had a better morphology than that of the control group. Furthermore, the amount of type I collagen was increased and overexpression of MMP-1 was reduced in the soybean extract group compared to vehicle group. Additionally, up-regulation of pro-inflammatory cytokines induced by UV irradiation was suppressed by dietary soybean extract treatment. It appears that soybean extract had a photoprotective effect, including anti-aging and anti-inflammatory effect, from UV-induced damage in not only human fibroblast, but also hairless mice. We confirmed that these effects were possibly due to promotion of collagen synthesis and inhibition of MMP-1 expression.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.45 no.2
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• pp.167-172
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• 2012

Minerals from marine materials such as deep ocean water and Dead Sea water have been used since ancient times. We made a mask pack sheet including deep ocean water and salt from the Dead Sea and evaluated the function of the mask pack sheet through animal study. Three full-thickness skin defects were made on the backs of Sprague-Dawley rats. The wounds were left untreated in group Con, and mask pack sheets including deep ocean water or deep ocean water and Dead Sea water were used as treatment for 20 min on the skin of animals in groups DP and DDP, respectively. We analyzed the gross, histological and biochemical findings. Groups DDP and DP showed decreases in wound size, as compared to group Con at 7 days after wound infliction. The histological findings revealed that wound healing had progressed further in groups DP and DDP than in group Con, with more rapid collagen deposition and regression of neutrophils. Also, the expression of vascular endothelial growth factor and transforming growth factor ${\beta}1$ were increased in groups DDP and DP compared with those in group Con at 3 days after wound infliction. Mask sheet packs including deep ocean water and Dead Sea salt affected wound healing by reducing the inflammatory phase and stimulated wound contracture by facilitating the deposition of collagen.

• The Korean Journal of Food And Nutrition
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• v.33 no.2
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• pp.174-182
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• 2020

Probiotics improve the immune system. However, the effects of its lactic acid bacteria on atopic dermatitis relief and inflammation improvement is not fully understood. Recently, one of the probiotics, Lactobacillus helveticus HY7801 (HY7801), was found to have an anti-inflammatory effect. In this study, we investigated the effects of HY7801 on atopic dermatitis-induced animal models. After four weeks of oral administration, the group treated with HY7801 showed amelioration of the atopic dermatitis compared to the group receiving placebo. In the HY7801 treated group, the epidermal hyper-proliferation and collagen deposition were inhibited compared to the placebo group, and the secretion amount of the inflammatory factors, such as TNF-α, IL-4 were reduced. In conclusion, these results suggest that HY7801 acts as a functional probiotic via amelioration of the atopic dermatitis such as a decrease of epidermal hyper-proliferation, and collagen deposition and anti-inflammatory effects.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.2
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• pp.129-143
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• 2024

Sulfur dioxide (SO₂), a novel endogenous gas signaling molecule, is involved in the regulation of cardiac function. Exerting a key role in progression of hyperthyroidism-induced cardiomyopathy (HTC), myocardial fibrosis is mainly caused by myocardial apoptosis, leading to poor treatment outcomes and prognoses. This study aimed to investigate the effect of SO₂ on the hyperthyroidism-induced myocardial fibrosis and the underlying regulatory mechanisms. Elisa, Masson staining, Western-Blot, transmission electron microscope, and immunofluorescence were employed to evaluate the myocardial interstitial collagen deposition, endoplasmic reticulum stress (ERS), apoptosis, changes in endogenous SO₂, and Hippo pathways from in vitro and in vivo experiments. The study results indicated that the hyperthyroidism-induced myocardial fibrosis was accompanied by decreased cardiac function, and down-regulated ERS, apoptosis, and endogenous SO₂-producing enzyme aspartate aminotransferase (AAT)1/2 in cardiac myocytes. In contrast, exogenous SO₂ donors improved cardiac function, reduced myocardial interstitial collagen deposition, up-regulated AAT1/2, antagonized ERS and apoptosis, and inhibited excessive activation of Hippo pathway in hyperthyroid rats. In conclusion, the results herein suggested that SO₂ inhibited the overactivation of the Hippo pathway, antagonized ERS and apoptosis, and alleviated myocardial fibrosis in hyperthyroid rats. Therefore, this study was expected to identify intervention targets and new strategies for prevention and treatment of HTC.

• International Journal of Stem Cells
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• v.15 no.2
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• pp.164-172
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• 2022

Background and Objectives: Despite advances in wound treatments, chronic diabetic wounds remain a significant medical challenge. Exosomes from mesenchymal stem cells (MSCs) and small molecule activators of nuclear factor erythroid 2-related factor 2 (Nrf2) have emerged as potential therapies for nonhealing diabetic wounds. This study aimed to evaluate the effects of exosomes from bone marrow-derived MSCs (BMSCs) alone, or in combination with a small molecule activator of Nrf2 on diabetic wound healing. Methods and Results: BMSCs and endothelial progenitor cells (EPCs) were isolated from the femur and tibia bone marrow of Sprague-Dawley (SD) rats and culture-expanded. Exosomes were harvested from the BMSC culture supernatants through ultracentrifugation. The effects of the exosomes and Nrf2 knockdown, alone or in combination, on EPC tube formation were evaluated. Streptozotocin-induced diabetic rats bearing a fresh full-thickness round wound were treated with the exosomes alone, or in combination with a lentiviral shRNA targeting Nrf2 (Lenti-sh-Nrf2) or tert-butylhydroquinone (tBHQ), a small molecule activator of Nrf2. Two weeks later, wound closure, re-epithelization, collagen deposition, neovascularization, and local inflammation were evaluated. BMSC exosomes promoted while Nrf2 knockdown inhibited EPC tube formation. BMSC exosomes accelerated wound closure, re-epithelization, collagen deposition, and neovascularization, and reduced wound inflammation in diabetic rats. These regenerative and anti-inflammatory effects of the exosomes were inhibited by Lenti-sh-Nrf2 but enhanced by tBHQ administration. Conclusions: BMSC exosomes in combination with a small molecule Nrf2 activator hold promise as a new therapeutic option for chronic diabetic wounds.