• Korean Journal of Veterinary Service
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• v.26 no.4
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• pp.345-359
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• 2003

A number of toxicants have been incriminated as a causing hepatic disease. Among many detrimental injury, alcohol has been noted for hepatitis, fatty liver, fibrosis, and hepatic cirrhosis. The purpose of this study was to develop animal model for hepatic fibrosis in pigs fed ethanol, and to search for a new anti-fibrogenic agent via this model. Twelve male Landrace pigs were divided into 3 groups of 4 animals each. Group 1, 2 and 3 were fed with active ceramic water only, ceramic water + liquid diet containing 15% ethanol and normal tap water + liquid diet containing 15% ethanol for 12 weeks, respectively. At week 12, all pigs were immediately sacrificed for collection each tissue and blood. Serologically, serum ALT and AST levels were significantly reversed in group 2, as compared to group 3. They were normal range in pigs of group 1. Microscopically, macrovesicular lipid droplets and moderate hepatocellular necrosis were evident in the tap water + ethanol fed group 3. However, the active ceramic water treated group 1 showed normal architecture. Moreover, in group 2, mild fatty changes and necrosis were observed in hepatocytes. Collagen fibers were increased in spaces surrounding periportal and interlobular connective tissues in the group 3 of tap water + ethanol, but collagen synthesis and its thickness of fibrotic septa connecting portal tracts were markedly reduced in the group 2 of ceramic water + ethanol. Myofibroblasts were detected mainly in the interlobular connective tissues of pig liver of group 3 treated ethanol and tap water. Few to no myofibroblasts were observed in groups 1 and 2. CYP2E1 was not or rarely detected in group 1 fed ceramic water. However, group 2 showed slightly activation of CYP2E1 in the area of pericentral vein, while CYP2E1 was significantly activated in group 3 fed tap water and ethanol. Based on the above data, we believe that we have developed a unique alcohol induced fibrosis model in pig, which will be useful in developing anti-fibrotic agents and drugs. Furthermore, the active ceramic water used in our study had an inhibitory and may be protective against ethanol induced hepatic toxicity and fibrosis.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.31 no.3 s.52
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• pp.227-235
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• 2005

Skin aging is not a disease nor an abnormal phenomenon but a collection of degenerative changes with age, characterized by skin dryness, wrinkle formation, and loss of skin elasticity. The skin wrinkles are caused by either genetically predisposed factors or environmental factors such as UV irradiation or physical/chemical stimulus. The histological manifestations of wrinkles are changes in both amount and integrity of elastic and collagen fibers. Here we report the isolation and characterization of 3 active compounds, prangenidin, 8-hydroxybergapten, and xanthotoxol from Angelica dahurica root. The anti-wrinkle activities of these compounds were also investigated.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.3
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• pp.511-515
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• 2002

Paeoniae radix has been considered as one of the most important crude drugs used in traditional oriental medicine and has been employed as a circulatory tonic in care of weakness, night sweats, and lumbar pain, etc. Platelet activation plays an important role in thrombosis and haemostasis. Active compounds for the inhibition of platelet activation from Paeoniae radix were extracted and fractionated into five fractions. Its fraction two and three of ethyl acetate extract inhibited the aggregation of washed rabbit platelets induced by collagen. Two active compounds, bezoyloxypaeoniflorin and paeoniflorin, were isolated from fraction two and three by silica gel column and high performance liquid chromatography. The chemical structures were determined by comparison of their proton and carbon nuclear magnetic resonance spectra. Benzoyloxypaeoniflorin showed strong inhibition at the concentration of 100 ug/mL against collagen-induced washed rabbit platelets aggregation. It is suggested that Paeoniae radix has become food material to prevent a cardiovascular disease.

• Journal of Microbiology and Biotechnology
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• v.17 no.2
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• pp.348-358
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• 2007

Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. $Na\ddot{i}ve\;CD4^+$ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, $TGF-{\gamma}$, and repressor of GATA, but more $IFN-{\gamma}$ and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove $na\ddot{i}ve$ wild-type $CD4^+\;T$ cells to differentiate into cells producing more IL-10 and $TGF-{\beta}$, but less $IFN-{\gamma}$ than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10-and $TGF-{\beta}$-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Th1-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.41-51
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• 2021

Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson's trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.55 no.6
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• pp.867-874
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• 2022

Osteoarthritis (OA) is an inflammatory disease due to wear caused by the continuous use of cartilage. Although many drugs for treating OA are being studied, they have side effects, such as digestive disorders and cardiovascular diseases. Glucosamine, a drug derived from natural products, is known to be less effective. Therefore, the marine organism, Sargassum fulvellum, was studied to determine whether it contains substances with a chondroprotective effect on the inflammatory response of chondrocytes induced by interleukin-1β (IL-1β). A 30% ethanol extract of S. fulvellum (SF30%EtOH) has therapeutic and few side effects. We first confirmed the presence of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), which is expressed during inflammatory reactions. We then examined the expression of collagen type II, which is the main component of the extracellular matrix and cartilage. Finally, the expression of extracellular matrix degrading enzymes, MMPs and ADAMTS-4 and -5, was confirmed. The results showed that SF30%EtOH reduced the expression levels of NO, iNOS, MMPs, and ADAMT-4 and -5, and increased the expression level of collagen type II in chondrocytes induced with IL-1β. Therefore, SF30%EtOH has a chondroprotective effect against inflammation, indicating its potential use for the prevention and treatment of OA.

• 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.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.69.1-69.11
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• 2023

Background: Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium Lyngbya majuscula found in the bed of the coral reef. Although KT suppresses cell division and inflammation, KT's mechanism of action in vascular smooth muscle cells (VSMCs) is unidentified. Therefore, our main aim was to investigate the impact of KT on vascular calcification for the treatment of cardiovascular disease. Objectives: Using diverse calcification media, we studied the effect of KT on VSMC calcification and the underlying mechanism of this effect. Methods: VSMC was isolated from the 6 weeks ICR mice. Then VSMCs were treated with different concentrations of KT to check the cell viability. Alizarin red and von Kossa staining were carried out to examine the calcium deposition on VSMC. Thoracic aorta of 6 weeks mice were taken and treated with different concentrations of KT, and H and E staining was performed. Real-time polymerase chain reaction and western blot were performed to examine KT's effect on VSMC mineralization. Calcium deposition on VSMC was examined with a calcium deposition quantification kit. Results: Calcium deposition, Alizarin red, and von Kossa staining revealed that KT reduced inorganic phosphate-induced calcification phenotypes. KT also reduced Ca⁺⁺-induced calcification by inhibiting genes that regulate osteoblast differentiation, such as runtrelated transcription factor 2 (RUNX-2), SMAD family member 4, osterix, collagen 1α, and osteopontin. Also, KT repressed Ca²⁺-induced bone morphogenetic protein 2, RUNX-2, collagen 1α, osteoprotegerin, and smooth muscle actin protein expression. Likewise, Alizarin red and von Kossa staining showed that KT markedly decreased the calcification of ex vivo ring formation in the mouse thoracic aorta. Conclusions: This experiment demonstrated that KT decreases vascular calcification and may be developed as a new therapeutic treatment for vascular calcification and arteriosclerosis.

• Tuberculosis and Respiratory Diseases
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• v.38 no.1
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• pp.1-7
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• 1991

To study the frequency of the underlying disease of the diffuse pulmonary infiltrates in korea, we ansalyzed retrospectively 982 patients who were seen at nine university hospitals and one general hospital in Seoul area. The results are folloing: 1) Among the total 982 patients, 490 patients were male and 492 patients were female. The mean age was 44.3 years. 2) The most common etiology was milliary tuberculosis (38%), which was followed by, idopathic pulmonary fibrosis (27%), pulmonary fibrosis associated with collagen-vascular disease (15%), and diffuse pulmonary infiltrates by malignancy (10%). 3) Amon the connective tissue disease which was accompanied by the interstitial lung disease, rheumatoid arthritis was the most common disease (43%), systemic lupus erythematosus was the 2nd (28%), and progressive systemic sclerosis was the 3re (16%). 4) Among 101 cases of malignant disease, lung was the most frequent primary site (31%), which was followed by stomach (28%), thyroid (16%), and breast (6%). 5) For the diagnosis of the underlying disease of pulmonary infiltrates, the transbronchial lung biopsy was performed in 21% of the patients and open lung biopsy was done in 7%.

• Clinical and Experimental Pediatrics
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• v.56 no.1
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• pp.19-25
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• 2013

Purpose: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD), and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. Methods: This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. Results: Factors associated with hepatic fibrosis (stiffness measurement >5.9 kPa Fibroscan) were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (>5.9 kPa). In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875) presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. Conclusion: APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.