• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.12 no.1
• /
• pp.88-92
• /
• 2009

Although transfusion of blood and plasma products are accepted as the principle means of transmission of HCV, other parenteral methods, such as acupuncture, tattooing needles, piercing, and surgery are possible methods of transmission of HCV. We managed a case of chronic hepatitis C acquired through ear piercing and acupuncture. A 10-year old girl presented with nausea, abdominal pain, and anorexia for 1 month. Her laboratory finding showed the following: AST/ALT, 865/1,290 IU/L; positive anti-HCV Ab; and HCV RNA. One year previously, she was treated with acupuncture for an ankle sprain and 2 years previously, she had her ears pierced. Laboratory findings of family members showed AST/ALT in the normal ranges, and negative anti-HCV Ab and HCV RNA. The pathologic findings of a liver biopsy revealed chronic hepatitis with mild lobular activity, moderate porto-periportal activity, and portal fibrosis. She was treated with pegylated interferon ${\alpha}$-2a and oral ribavirin for 6 months, after which the clinical symptoms and laboratory findings improved.

• Korean Journal of Veterinary Research
• /
• v.43 no.4
• /
• pp.683-688
• /
• 2003

Caffeine (1,3,7-trimethylxanthine), a central nervous system stimulant, is contained in various foods, beverages and over-the-counter medications. Sulfadimethoxine (SDM) is one of the anti-thyroid agents and induces proliferation of thyroid capsule in two stage thyroid carcinogenesis model using N-bis(2-hydroxypropyl)nitrosamine (DHPN). In this study, we examined the effect of caffeine on fibrous proliferation of thyroid capsule in DHPN and SDM-treated rats. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2,800 mg/kg, body weight). Starting one week thereafter, SDM (1,000 ppm in drinking water) with or without caffeine (1,500 ppm in diet) was administered for 12 weeks. All animals were autopsied and histopathological examination of the thyroid glands was performed. Thyroid follicular proliferative changes were induced in all rats treated with DHPN+SDM. In addition, the proliferation of perithyroidal fibrous tissue and pleomorphic thyroid follicular cells within the capsule were observed in DHPN+SDM treated group. Caffeine would not be related to these lesions in this experimental condition. although pentoxifylline, a methyl xanthine derivative, has an anti fibrotic effects.

• BMB Reports
• /
• v.53 no.11
• /
• pp.600-604
• /
• 2020

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.

• The Journal of Korean Medicine
• /
• v.36 no.2
• /
• pp.21-35
• /
• 2015

Objectives: The purpose of this study was to examine the efficacy of Picrorrhizae Rhizoma (PR) aqueous extracts on the formalin-induced paw chronic inflammation in mice. Methods: PR extracts (500, 250 and 125mg/kg) or distilled water (DW) were orally administered once a day for 10 days to formalin-injected chronic inflammatory mice. The paw thicknesses and volumes were measured daily and the paw wet-weight and histological profiles were conducted at termination with paw tumor necrosis factor (TNF)-${\alpha}$ contents measurement. The anti-inflammatory effects of PR extracts were compared with dexamethasone. Results: In DW treated control group, the paw thickness, paw wet-weights and paw TNF-${\alpha}$ contents were markedly increased. Severe chronic inflammation signs such as severe fibrosis, the formation of necrotic debris, and infiltration of inflammatory cells were detected in histopathological observations. However, these formalin-induced changes were dramatically decreased by treatment of dexamethasone and all three different dosages of PR extracts. The anti-inflammatory effects of PR at highest dose were slighter than that of dexamethasone, but it did not show any harmful effects on the body weight contrary to dexamethasone. Conclusion: These results suggest that PR extracts have safe and favorable effects on formalin-induced chronic inflammation.

• Preventive Nutrition and Food Science
• /
• v.20 no.3
• /
• pp.153-161
• /
• 2015

Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that have important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Marine plants are on the rise for their potential to provide natural products that exhibit remarkable health benefits. In this context, brown algae species have been of much interest in the pharmaceutical field with reported instances of isolation of bioactive compounds against tumor growth and MMP activity. In this study, eight different brown algae species were harvested, and their extracts were compared in regard to their anti-MMP effects. According to gelatin zymography results, Ecklonia cava, Ecklonia bicyclis, and Ishige okamurae showed higher inhibitory effects than the other samples on MMP-2 and -9 activity at the concentrations of 10, 50, and $100{\mu}g/mL$. However, only I. okamurae was able to regulate the MMP activity through the expression of MMP and tissue inhibitor of MMP observed by mRNA levels. Overall, brown algae species showed to be good sources for anti-MMP agents, while I. okamurae needs to be further studied for its potential to yield pharmaceutical molecules that can regulate MMP-activity through cellular pathways as well as enzymatic inhibition.

• Experimental and Molecular Medicine
• /
• v.50 no.11
• /
• pp.1.1-1.10
• /
• 2018

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.

• Nutrition Research and Practice
• /
• v.18 no.3
• /
• pp.325-344
• /
• 2024

BACKGROUND/OBJECTIVES: Kaempferol (Ka) is one of the most widely occurring flavonoids found in large amounts in various plants. Ka has anti-obesity, antioxidant, and anti-inflammatory effects. Despite the numerous papers documenting the efficacy of Ka, some controversy remains. Therefore, this study examined the impact of Ka using 3T3-L1 and high-fat diet-induced obese mice. MATERIALS/METHODS: 3T3-L1 cells were treated with 50 μM Ka from the initiation of 3T3-L1 differentiation at D0 until the completion of differentiation on D8. Thirty male mice (C57BL/6J, 4 weeks old) were divided into 3 groups: normal diet (ND), high-fat diet (HFD), and HFD + 0.02% (w/w) Ka (Ka) group. All mice were fed their respective diets ad libitum for 16 weeks. The mice were sacrificed, and the plasma and hepatic lipid levels, white adipose tissue weight, hepatic glucose level, lipid level, and antioxidant enzyme activities were analyzed, and immunohistochemistry staining was performed. RESULTS: Ka suppressed the hypertrophy of 3T3-L1 cells, and the Ka-supplemented mice showed a significant decrease in perirenal, retroperitoneal, mesenteric, and subcutaneous fat compared to the HFD group. Ka supplementation in high-fat diet-induced obese mice also improved the overall blood lipid concentration (total cholesterol, non-high-density lipoprotein-cholesterol, phospholipids, and apolipoprotein B). Ka supplementation in high-fat-induced obesity mice reduced hepatic steatosis and insulin resistance by modulating the hepatic lipid (glucose-6-phosphate dehydrogenase, fatty acid synthase, malic enzyme, phosphatidate phosphohydrolase, and β-oxidation) activities and glucose (glucokinase, phosphoenolpyruvate carboxykinase, and G6pase)-regulating enzymes. Ka supplementation ameliorated the erythrocyte and hepatic mitochondrial H₂O₂ and inflammation levels (plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6, and interferon-gamma and fibrosis of liver and epididymal fat). CONCLUSION: Ka may be beneficial for preventing diet-induced obesity, inflammation, oxidative stress, and diabetes.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.4
• /
• pp.823-834
• /
• 1998

Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

• The Journal of Internal Korean Medicine
• /
• v.26 no.4
• /
• pp.853-863
• /
• 2005

Object : This study was performed to investigate the anti-fibrogenic effect of Artemisiae Capillaris Herba(ACH) on cultured rat hepatic stellate cells. Methods : Hepatic Stellate Cells were obtained from a 350gm Sprague-Dawley rat by tissue perfusion system, and the cells for the study were selected after 3 passages of culture on non-coated plastic culture dishes which enable the cells to activate, thus producing collagens in the cell media. Cells were treated with various concentrations of Artemisia Capillaris Herba(ACH) extract powder for 24 or 48 hours. After the treatment, Soluble collagen, procollagen levels and the mRNA of the procollagen type I C were measured by using assay kit and RT-PCR method. Results : Procollagen production by the hepatic stellate cells decreased after the treatment in a time-dependent dose-dependent manner. The mRNA expression decreased consistently with the volume of the secreted procollagen which indicates the herb hat inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. Conclusion : These results suggest that ACH is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.2
• /
• pp.193-201
• /
• 2018

Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.