• Biomedical Science Letters
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• v.25 no.3
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• pp.282-287
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• 2019

Skin flap necrosis remains a major complication of reconstructive surgery. Euterpe oleracea Mart., popularly known as "acai berry" contains hydroxybenzoic acid, antioxidant polyphenolics and anthocyanins. These and other compounds within the acai berry confer anti-inflammatory and anti-oxidative effects. In this current study, we evaluated the protective effect of acai berry extracts on survival of random-pattern skin flaps in a murine model by histologic analysis. ICR mice were subjected to skin elevation surgery and orally administered acai berry extract (100 mg/kg) daily for 7 days. Tissues were stained with hematoxylin-eosin or Masson's trichrome to observe tissue integrity and collagen deposition. In addition, $TGF-{\beta}$ and VEGF was stained by immunofluorescence to determine anti-inflammatory cell infiltration and neovascularization, respectively. We found a decrease in inflammatory cell infiltration and increase in collagen deposition in the acai berry extract treated mice compared to control mice. Immunofluorescence staining reveal a higher number of $TGF-{\beta}$ positive cells and enhanced VEGF staining in the acai berry extract treated mice. The results from this study indicate that oral uptake of acai berry extract can promote healing and survival of surgical skin flaps in mice providing an augmentative therapeutic approach to enhancing skin flap survival.

• Proceedings of the Korean Vacuum Society Conference
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• 2010.02a
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• pp.397-397
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• 2010

Bone is considered as hierarchically organized biocomposites of organic (collagen) and inorganic (hydroxyapatite) materials. The precise structural dependence between hydroxyapatite (HAp, $Ca_{10}(PO_4)_6(OH)_2)$ crystals and collagen fibril is critical to unique characteristics of bone. To meet those conditions and obtain optimal properties, it is essential to understand and control the initial growth mechanisms of hydroxyapatite at the molecular level, such as other nano-structured materials. In this study, collagen fibrils were prepared by adsorbing native type I collagen molecules onto hydrophobic surface. Hydrophobicity was introduced on the Si wafer surface by using PECVD (plasma enhanced chemical vapor deposition) method and cyclohexane as a precursor. Biomimetic nucleation and growth of HAp on the self-assembled collagen nanofibrils were occurred through incubation of the sample in SBF (simulated body fluid). Chemical and morphological evolution of HAp nanocrystals was investigated by surface-sensitive analytical techniques such as ToF-SIMS (Time-of-Flight Secondary Ion Mass Spectrometry) and AFM (Atomic Force Microscopy) in the early growth stages (< 24 hrs). The very initial stages (< 12 hrs) of mineralization could be clearly demonstrated by ToF-SIMS chemical mapping of surface. In addition to ToF-SIMS and AFM measurement, scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction analysis were conducted to characterize the HAp layer in the late stages. This study is of great importance in the growth of real bone-like materials with a structure analogous to that of natural bones and the development of biomimetic nanomaterials.

• Journal of Pharmacopuncture
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• v.25 no.3
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• pp.258-267
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• 2022

Objectives: Hypertrophic scars (HSs) are caused by abnormal wound healing. To date, no standard treatment has been made available for HSs. Scrophularia striata has been reported to accelerate wound healing and has the potential to prevent HS formation. In this study, we investigated the anti-scarring effects of S. striata extract (SSE) in a rabbit ear model of scarring. Methods: In this study, New Zealand white rabbit (weight: 2.3-2.5 kg) were used. In the prevention phase of the study, three test groups received 5%, 10%, and 15% ointments of SSE in the Eucerin base, the fourth group received Eucerin, and the fifth group received no treatment. The samples were obtained on day 35 after wounding. In the treatment phase of the study, the test groups received an intralesional injection of SSE (5%, 10%, and 15%), the fourth group received an intralesional injection of triamcinolone, the fifth group received a solvent (injection vehicle), and the sixth group received no treatment. To evaluate the anti-scarring effects of SSE, the scar elevation index (SEI), epidermis thickness index (ETI), collagen deposition, and MMP2 and MMP9 gene expression were evaluated. Results: A significant reduction in SEI, ETI, and collagen deposition was noted in animals treated with SSE compared with the control groups. In addition, topical SSE stimulated MMP2 and MMP9 gene expression. Conclusion: The findings of this study demonstrate the potential for SSE in the prevention and treatment of HS. SSE could be prepared as an appropriate formulation to treat wounds and prevent abnormal scarring.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.437-448
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• 2023

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

• The Korea Journal of Herbology
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• v.37 no.6
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• pp.9-17
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• 2022

Objective : In modern society, liver diseases such as liver fibrosis are on the rise as inflammation and wound healing processes of the liver are repeated due to factors such as drinking, smoking, and stress. This study was conducted to evaluate the effect of Saenggangeonbi-tang (SGGBT) on thioacetamide (TAA)-induced liver fibrosis. Methods : The mice were divided into 4 groups for examination (n=6): Normal group (Nor), distilled water-treated liver fibrosis mice (Con), silymarin 50 mg/kg-treated liver fibrosis mice (Sily), SGGBT 200 mg/kg-treated liver fibrosis mice (S200). Liver fibrosis was established in the mice via TAA for 8 weeks (1 week 100 mg/kg, 2,3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg, three times a week, intraperitoneal injection) and they were administered silymarin and SGGBT (every day, oral administration) with the TAA. Results : SGGBT significantly decreased the levels of aspartate aminotransferase, alanine aminotransferanse, ammonia, and myeloperoxidase in serum increased by liver fibrosis. As a result of confirming H&E and MT staining, it was confirmed that SGGBT reduced damage and inflammatory cell infiltration in liver tissue, and alleviated changes in collagen fiber deposition and histological fibrosis. Also, it was confirmed through PAS staining that it reduced glycogen deposition in liver tissue. In addition, SGGBT significantly decreased the NADPH oxidases as well as significantly modulated the expression of MMP-2 and TIMP-2. Conclusions : These results suggest that SGGBT regulates the expression of MMP/TIMP protein through inhibition of oxidative stress and alleviates liver fibrosis by reducing collagen and glycogen deposition in liver tissue.

• Advances in Traditional Medicine
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• v.2 no.2
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• pp.94-100
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• 2002

Liver cirrhosis is characterized by hyperaccumulation of fibrous tissue components and is commonly observed in latter or terminal states of chronic hepatic diseases. In this study, the antifibrotic effects of GLM001 on liver cirrhosis were examined in bile duct ligated rats and patients with hepatic diseases. GLM001 (250 mg/kg rat weight/ day) was administrated to cirrhotic rats for 4 weeks and to humans for 14 weeks. Bile duct ligated rats significantly increased liver collagen content and biochemical markers of hepatic injury. Liver histology showed collagen fiber deposition was increased and the normal architecture was lost with large zones of necrosis being observed frequently. GLM001 administrated rats showed significantly decreased liver collagen content, and accumulation of collagen fiber in histological analysis. Patients, who were treated with GLM001, showed decreases in biochemical markers of hepatic diseases. These results demonstrate the usefulness of GLM001 as an antifibrotic agent for liver cirrhosis.

• The Journal of Korean Medicine
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• v.31 no.2
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• pp.19-35
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• 2010

Objectives: This study was carried out to find the effects of Changchuldoin-tanggamibang (hereinafter referred to CDIT) on the inhibition of arthritis induced by collagen on DBA/1J mouse. Methods: The experimental mice were divided into four groups: normal group (Nr), control group (CIA-CT), methotrexate group (CIA-MTX), and Changchuldoin-tanggamibang group (CIA-CDIT). Cytotoxicity, hepatotoxicity, arthritis index, value of immunocytes in draining lymph node and paw joint, and rheumatoid factor (IgG, IgM) in serum were measured in vivo. Results: 1. Cytotoxicity against hFCs was not shown in any concentration. 2. Hepatotoxicity was low in the CDIT-treated group compared with the MTX group. 3. The arthritis index decreased significantly. 4. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was a significant decrease in paw joint. 5. In lymph nodes, CD19+, CD3+, CD4+, CD8+, CD3+/CD8+, CD3+/CD69+, CD4+/CD25+, CD3+/CD49b+, and CD4+/CD44+ cells increased significantly, while B220+/CD23+, and CD11c+/MHCII+ cells decreased significantly. 6. In joints, CD3+, CD4+, CD4+/CD25+, and CD11b+/Gr-1+ cells decreased significantly. 7. The level of IgG decreased and the level of IgM significantly decreased compared with the control. 8. Anti-collagen II in serum decreased compared with the control. 9. Around the joint of the CDIT group, infiltration of inflammation, synovial hyperplasia, invasion of cytokine, of cartilage, deposition of collagen and synovial injury decreased compared with the control in histopathologic observation (HE, MT staining). Conclusions: Comparison of the results for this study showed that CDIT had immunomodulatory effects. We expect that CDIT could be used as a effective drug for not only rheumatoid arthritis but also another auto-immune diseases. Therefore, we have to survey continuously, looking for effective substances and mechanisms in the future.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.401-411
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• 2015

Aldose reductase (AR) is known to play a crucial role in the mediation of diabetic and cardiovascular complications. Recently, several studies have demonstrated that allergen-induced airway remodeling and ovalbumin-induced asthma is mediated by AR. Epalrestat is an aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Whether AR is involved in pathogenesis of pulmonary fibrosis and whether epalrestat attenuates pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. The expression of AR, TGF-${\beta}_1$, ${\alpha}$-SMA and collagen I was analyzed by immunohistochemisty, real-time PCR or western blot. In vivo, epalrestat treatment significantly ameliorated the bleomycin-mediated histological fibrosis alterations and blocked collagen deposition concomitantly with reversing bleomycin-induced expression up-regulation of TGF-${\beta}_1$, AR, ${\alpha}$-SMA and collagen I (both mRNA and protein). In vitro, epalrestat remarkably attenuated proliferation of pulmonary fibroblasts and expression of ${\alpha}$-SMA and collagen I induced by TGF-${\beta}_1$, and this inhibitory effect of epalrestat was accompanied by inhibiting AR expression. Knockdown of AR gene expression reversed TGF-${\beta}_1$-induced proliferation of fibroblasts, up-regulation of ${\alpha}$-SMA and collagen I expression. These findings suggest that AR plays an important role in bleomycin-induced pulmonary fibrosis, and epalrestat inhibited the progression of bleomycin-induced pulmonary fibrosis is mediated via inhibiting of AR expression.

• The korean journal of orthodontics
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• v.28 no.1 s.66
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• pp.1-15
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• 1998

Adult wound healing is accompanied with inflammation and eventual scar formation, whereas fetal wounds heal rapidly by mesenchymal proliferation without significant inflammatory cell participation and with minimal or no scar formation. The cellular mechanisms underlying these differing forms of wound healing are unknown but the extracellualr matrix through its effects on cell function, may play a key role. Therefore the purpose of this study is to investigate the spatial and temporal deposition of several component of extracellular matrix, which are known to be involved with scar formation, in the artificially created cleft lip wound healing of fetuses. The author had undergone hysterotomy and created cleft lip-like defects on fetuses of New Zealand White Rabbit in mid-third trimester(24 days). Fetuses were divided into the repaired group, the unrepaired group and the sham-operated control group. At 1, 2, 3, 5, 7 days after procedure, fetuses were obtained by Caeserem section. After documenting the viability of fetuses, they were photographed to compare size and facial morphology and sectioned for histological examination by H & E stain and spatial and temporal deposition of collagen typeI, III, IV, V and fibronectit laminin by immunohistochemical method. The findings are summarized as follows 1. There were lack of inflammation in the repaired and the unrepaired group during experimental periods. 2. The reepithelialization of the unrepaired group was slower than that of the repaired group. 3. Collagen I, III, V were found from post-op. third day. There were no difference of distribution in the control, the repaired and the unrepaired group. Collagen types I, III, V were present in all groups with restoration of the normal collagen pattern in the fetus. This implies that lack of scarring in fetal wounds is due to the difference of collagen organization pattern within wound and not simply lack of collagen formation. 4. Collagen IV was slightly increased at post-op. third day and decreased after post-op. fifth day. Eventually there were no differences in the control, the repaired and the unrepaired group. Lminin was found at post-op. fifth day and maintained staining density until post-op. seventh day. There were no differences in the control, the repaired and the unrepaired group. According to staining of laminin and collagen type IV in epithelial basement membrane, formation of epithelial basement membrane was not completed until reepithelialization was finished. 5. According to staining of laminin and collagen type IV, there were no increase of neovascularity in the repaired and the unrepaired group. 6. Fibronectin was increased until post-op. third day at fibrin clot, wound base and margin and decreased after post-op. fifth day. Eventually, there were no differences in the control, the repaired and the unrepaired group. So it implies fibronectin plays a role as provisional matrix for fetal wound healing.

• The Journal of Korean Medicine
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• v.23 no.3
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• pp.43-53
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• 2002

Objectives : To investigate the photoprotective effects and efficacy of Jaummi-dan (Ciyinmei-dan) on UV damage to animal skin/fibroblast cultures. Methods and Results : Hairless mice were orally administered Jaummi-dan (Ciyinmei-dan) extract and irradiated with UV for four weeks. In the Jaummi-dan (Ciyinmei-dan) treated group, a better skin appearance and less wrinkles were observed when compared to the control group. In addition, immunostaining for type 1 pN collagen showed that the amount of collagen deposition was higher in the Jaummi-dan (Ciyinmei-dan) treated group. The interstitial collagenase was measured in the cultured medium of fibroblasts after UVB irradiation using ELISA for MMP-l. Jaummi-dan (Ciyinmei-dan) treatment resulted in a significant decrease in MMP-1 secretion compared to the UVB-irradiated, untreated group. Conclusions : The results of our study indicate that orally administered Jaummi-dan (Ciyinmei-dan) seems to have photoprotective effects on UV damaged hairless mouse skin partly due to an inhibitory effect on collagen breakdown.