Muscle atrophy, characterized by a reduced number and size of myofibers, occurs due to immobilization, aging, and several chronic diseases. Leonurus japonicus, belonging to the Labiatae family, is widely used as a traditional medicine in Korea, China, and Japan. Previous studies have reported that L. japonicus has various physiological activities, such as anti-bacteria, anti-cancer, and liver protection. Leonurine, which is a major bioactive in L. japonicas, is known to possess biological effects including anti-inflammation, anti-fibrosis, anti-angiogenesis, and anti-diabetes. However, the preventive effects of L. japonicas and leonurine on muscle have not been reported. The current study aimed to determine the inhibitory effects of standardized L. japonicus extract (LJE) and leonurine on muscle atrophy by clarifying their underlying molecular mechanisms in tumor necrosis factor-alpha (TNF-α)-stimulated L6 myotubes. LJE and leonurine stimulated the phosphatidylinositol 3-kinase/Akt pathway that was reduced by TNF-α treatment. LJE and leonurine not only increased the mammalian target of rapamycin pathway for protein anabolism but also decreased the mRNA expression of E3 ubiquitin ligases by blocking the translocation of Forkhead box O, which is closely linked with proteolysis. Additionally, LJE and leonurine alleviated inflammatory responses by downregulating TNF-α and interleukin-6 mRNA expression and reducing the protein expression of nuclear factor-kappa B, a major transcriptional factor of proinflammatory cytokines. Collectively, LJE and leonurine have potential as therapeutic candidates for inhibiting the development of skeletal muscle atrophy by activating the PI3K/Akt pathway and reducing inflammatory responses.
Background: Nonalcoholic steatohepatitis (NASH) is one of the main chronic liver diseases. NASH is identified by lipid accumulation, inflammation, and fibrosis. Jinan Red Ginseng (JRG) and licorice have been widely used because of their anti-inflammatory and hepatoprotective effects. Hence, this study assessed JRG and licorice extract mixtures' effects on NASH progression. Methods: Palmitic acid (PA) and the western diet (WD) plus, high glucose-fructose water were used to induce in vitro and in vivo NASH. Mice were orally administered with JRG-single (JRG-S) and JRG-mixtures (JRG-M; JRG-S + licorice) at 0, 50, 100, 200 or 400 mg/kg/day once a day during the last half-period of diet feeding. Results: JRG-S and JRG-M reduced NASH-related pathologies in WD-fed mice. JRG-S and JRG-M consistently decreased the mRNA level of genes related with inflammation, fibrosis, and lipid metabolism. The treatment of JRG-S and JRG-M also diminished the SREBP-1c protein levels and the p-AMPK/AMPK ratio. The FAS protein levels were decreased by JRG-M treatment both in vivo and in vitro but not JRG-S. Conclusion: JRG-M effectively reduced lipogenesis by modulating AMPK downstream signaling. Our findings suggest that this mixture can be used as a prophylactic or therapeutic alternative for the remedy of NASH.
Chronic alcoholism is considered a common cause of malnutrition. Especially, micronutrient deficiency may playa critical role in the incidence of alcoholic liver diseases. This study was conducted to investigate the effect of folate deficiency and ethanol consumption on cholesterol metabolism and the antioxidative system in rats. Plasma concentration of total cholesterol was increased by ethanol administration in folate-fed rats. HDL-cholesterol tended to be higher in the folate-fed group, but it was not significant. The plasma and hepatic levels of malondialdehyde were increased after chronic ethanol feeding, but dietary folate depressed the plasma malondialdehyde content of rats. Ethanol or folate feeding did not significantly change alcohol dehydrogenase activity. But folate feeding increased catalase activity in ethanol-fed rats. There was no significant change in superoxide dismutase activity among the experimental groups. Glutathione peroxidase activity tended to decrease by chronic ethanol feeding, but dietary folate did not affectthe glutathione peroxidase activity of chronic ethanol-fed rats. Glutathionine-S-transferase activity was not affected by ethanol feeding or folate deficiency. The plasma and hepatic levels of retinol decreased after chronic ethanol feeding. The hepatic level of retinol significantly decreased in ethanol-fed rats by folate deficiency. The plasma level of $\alpha$-tocopherol tended to be low in the folate deficient group with ethanol feeding, but there was no difference among the experimental groups in the hepatic level of $\alpha$-tocopherol. These results demonstrate that chronic ethanol consumption changes the plasma cholesterol metabolism and antioxidative system of rats, and optimal folate feeding in ethanol-fed rats exerts protective effects to some extent.
Recently interests on raw-food diets are rapidly increasing in relation to chronic diseases prevention in Korea, but studies on raw-food diets have been hardly performed by nutritionists. This study was performed to investigate the effects of low-calorie diets using a raw-food formula in the form of freeze-dried powder on obesity and its complications in the obese women (body mass index (BMI) $\geq$ 25kg/㎡) for eight weeks. Forty premenopausal women (mean BMI 28.04kg/㎡, mean age 28.33years old) participated in this diet intervention, and were controlled by eating 1 regular meal, 1-2 snacks and 2 raw-food formula (140kcal/pack) meals a day within the 1500-1300kcal ranges. Anthropo-mentric measurements, body compositions, physical exercise, and obesity-related risk factors were assessed before (the initial), during (the 4th week) and after (the 8th week) the study. All the data was analyzed by paired t-test, repeated measures ANOVA, and nonparametric rank test at p<0.05 level. Obesity was significantly increased during this study, and it was decreased in weight (-4.59%, p<0.000), BMI (-4.56%, p<0.000), body fat percent (-6.18%, p<0.000), fat mass (-10.19%, p<0.000), waist and hip circumferences(-5.69%, p<0.000 and -2.55%, p<0.000) and WHR (-3.24%, p<0.000). Energy expenditure of physical exercise was increased as much as 70kca1/day during the study (p=0.000), but it did not have any correlations with weight loss and changes of body compositions. Biochemical measurements including blood triglyceride(p <0.006) and leptin(p<0.000) levels were significantly decreased, LDL cholesterol level was increased(p<0.05), but all the blood lipid levels were in the normal ranges. Fatty liver echogenicity and menstrual irregularity were improved after the diet intervention(p<0.000 and p<0.034). In conclusion, this B-week low-calorie diet intervention using raw-food formula was effective for obese premenopausal women in reducing obesity and its risk factors so as not to proceed towards comorbidities. However, the variation of blood lipid levels should be observed for a longer Period.
The previous extensive in vitro studies on the antioxidative activities of a number of Korean grains, vegetables, seaweeds and mushrooms, and the various combinations of these food source exhibited a wide range of antioxidative activities, and four food mixtures composed of 5 kinds of foods (5A, 5B, 5C and 5D) were designed from 16 selective foods showing. high antioxidant effect, in vitro, to find the good combinations for the meal planning. Mixture 5B or 5C contained very high levels of total flavonoid and polyphenol, and ethanol extract from 5A, 5B or 5C showed very strong inhibitory effects against in vitro $Fe^{2+}-induced$ lipid peroxidation and ethanol extract from 5B or 5C showed remarkable DPPH radical scavenging effect and lipid peroxide-protein conjugation inhibition effect. And in vivo study was also carried out with two mixtures (5B, 5C). Powders (P5B, P5C) or ethanol extracts (E5B, E5C) of these mixtures were supplemented to Sprague-Dawley rats fed on high fat $(15\%)-high$ cholesterol $(1\%)$ semipurified diet for 5 weeks. The total antioxidant power in serum was significantly higher in P5B, P5C, E5B and E5C groups than in high fat control group, and $ascorbate-Fe^{2+}-induced$ TBARS was significantly lowered by E5B supplementation in rat liver. In liver tissue, Cu, Zn-SOD activity was significantly higher in P5B and E5B groups than in high fat control group, while catalase or GSH-peroxidase (GPx) activity was not changed by any supplementations. In kidney, Cu, ZnSOD activity was significantly higher in P5B group than in high fat control group, while GPx activity was not changed by any supplementations. Taken together, mixture 5B and 5C showed very strong antioxidative effects both in vitro and in vivo. Therefore, the ingredient Korean foods of 5B and 5C could be recommended to take a lot together for prevention from age-related chronic diseases.
The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require $CD4^{+}CD25^{+}$ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.
Park, Yong-Jin;Kim, Young-Chul;Lee, Jang-Hoon;Woo, Hong-Jung
The Journal of Korean Medicine
/
v.19
no.1
/
pp.145-164
/
1998
The purpose of this study is to evaluate the effect of Injinchunggantang-derivative on proliferation of hepatocyte in rats. Cell viability is studied by MTI assay. The gene related to cell replication such as p53, waf1, bcl-2 and $bcl-_{X_L}$ is quantitized by quantitative RT-PCR and the proteins coded by these genes are studied by Western blotting. The results are as follows. 1. The hepatocytes cultured in medium with lnjinchunggantang-derivative showed better viability compared with control grroup in MTI assay, and the hepatocytes cultured in medium with the Injinchunggantang-derivative-and-ethanol-mixed group showed better viability than the hepatocytes cultrued in 10% ethanol culture medium(control group), noting that Injinchunggantang-derivative has protective effect on hepatocyte injury. There was no dose- and time-dependence. 2. In quantitative RT-PCR, i) Bel-2 gene increased significantly both in Injinchunggantang-derivative group and in Injinchunggantang-derivative-and-ethanol-mixed group, while it showed no significant increase or decrease in other group. ii) $Bcl-_{X_L}$ gene increased significantly in Injinchunggantang-derivative group as well as in Injinchunggantang-deri vative-and-ethanol -mixed group. iii) P53 gene showed no significant increase or decrease in hepatocytes cultured in medium with 10% ethanol and in hepatocytes cultured in medium with Injinchunggantang-derivative-and-ethanol-mixed group, suggesting that 10% ethanol induced cell toxicity, thus increased p53 gene expression. iv) Wafl gene showed no significant increase or decrease in hepatocytes cutured in medium with Injinchtrnggantang-derivative, while increased in hepatocytes cultured in medium with 10% ethanol and in hepatocytes cultured in medium with Injinchtrnggantang-derivative-andethanol-mixed group, suggesting that 10% ethanol induced cell toxicity increased wafl gene expression. 3. In the study on protein by western blotting, the band of bcl-2 and $bcl-_{X_L}$ were widened in Injinchtrnggantang-derivative group. Especially the amount of $bcl-_{X_L}$ increased significantly compared with other groups. But in the study on p53 and wafl, there was no significant difference among those groups. Above study shows that Injinchunggantang-derivative has good effect on cell viability and that the genes resistant to cell death such as bcl-2 and $bcl-_{X_L}$ are induced by Injinchunggantang-derivative to resist to cell death by toxic agent And this is reconfirmed in protein study using' western blotting: These results suggest that Injinchunggantang-derivative has inhibitory effect on cell death as well as protective effect on hepatocyte. Therefore this prescription is recommended in various liver diseases such as chronic liver disease and-induced hepatic injury.
Purpose: Autoimmune hepatitis is a chronic inflammatory liver disease with unknown cause that is characterized by liver histology, circulating autoantibodies and increased levels of immunoglobulin G. Only sporadic reports are available on autoimmune hepatitis in children. The aim of this study was to evaluate the clinical, biochemical, and histological features, and the long-term outcome of autoimmune hepatitis in Korean children. Methods: We reviewed the medical records of 14 children diagnosed as having autoimmune hepatitis at Seoul National University Children's Hospital from 1990 to 2004, and analyzed clinical, biochemical, and histological features, and clinical outcomes. Results: Mean age at diagnosis was 9 years and 11 of the 14 children were female. Six children presented with acute hepatitis-like manifestations. Jaundice and fatigue were the most common symptoms. Other autoimmune diseases accompanied in 6 children. Anti-nuclear antibody was detected in 13 patients and anti-smooth muscle antibody was positive in 8. All 14 patients were type 1 autoimmune hepatitis. The main histologic findings were interface hepatitis, rosette formation, and cirrhosis. Clinical and biochemical features were improved in six patients treated with ursodeoxycholic acid. Eight patients were treated with corticosteroid alone or in combination with azathioprine and five of them are in biochemical remission. Conclusion: Autoimmune hepatitis is an inflammatory liver disease, which has a favorable long-term outcome if it is diagnosed and treated promptly. Therefore, autoimmune hepatitis should be suspected in children with chronic hepatitis of unknown etiology, especially in female patients who show hypergammaglobulinemia or some clinical features of autoimmune disease.
Seo, Mi Hyun;Kim, Soung Min;Oh, Jin Sil;Myoung, Hoon;Lee, Jong Ho
Maxillofacial Plastic and Reconstructive Surgery
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v.34
no.5
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pp.332-336
/
2012
Purpose: The third molar extraction is one of the mostly performed procedures in the department of oral and maxillofacial surgery. In most of dental clinic or hospital, the third molar extraction used to be frequently performed in an office-based surgery, and most patients did not have specific medical history with young ages. Medical history taking are dependent on the only way by asking to the patients about their individual conditions. Therefore, as the specialists of the oral and maxillofacial surgery in the field of dentistry, we suggest a new policy that the preoperative lab must be performed routinely before extraction of the third molar. Methods: This study is based on 1,096 patients who have been managed with third molar extractions, from March 2008 to September 2011 by a single surgeon. The preoperative lab, including complete blood count, coagulation panel, chemistry and serology, was performed before any surgical procedures. The results were informed to the patients regardless of their abnormalities, and any abnormalities related to the surgical procedures, such as platelet count and coagulation factors, were checked and corrected safely. Results: Through the preoperative blood test, systemic diseases that the patients had not recognized before, such as anemia, leukopenia, fatty liver and chronic renal disease, were identified. Patients with acute or chronic leukemia, Hepatitis B, and HIV positive, were also detected as a small number. Also, the possibilities of the cross-infection between dentists and patients or between patients and patients, and any other emergency situations can be prevented; as well as the public health condition can be improved, too. The patients were satisfied with low cost preventive blood test and high quality of medical services. Conclusion: Therefore, routine medical lab testing, including history taking are needed before an office-based minor surgery, such as third molar extractions, and these results were suggested as a new policy in the field of dentistry.
Fawzy, Mariam M;Wahid, Ahmed;Nazmy, Maiiada H;Hashem, Mohamed;Waked, Imam;Abdelwahab, Sayed F
Asian Pacific Journal of Cancer Prevention
/
v.17
no.4
/
pp.2093-2097
/
2016
Background: HCV is a major global health problem. IL-27 is a member of the IL-6/IL-12 cytokine family with a broad range of anti-inflammatory properties. Recent studies highlighted the effect of a SNP in the IL-27 promoter region on modulating the progression of infectious diseases and individual responses to therapy. Aim of the work: The present study investigated the potential role of (-964 A/G) SNP in the promoter region of IL-27p28 gene (alleles rs153109) on the outcome of HCV infection among genotype 4a infected patients. Materials and Methods: HCV genotyping confirmed that all of the HCV-infected patients had genotype 4a infection. Genomic DNA was extracted from 111 patients with chronic HCV infection, 42 spontaneous resolvers (SR) and 16 healthy controls. IL- 27p28.rs153109 genotyping was assessed using PCR-RFLP then confirmed by DNA sequencing. Results: The frequency of IL-27-p28.rs153109AA, AG, and GG genotypes among chronically infected subjects were 74.8 %, 25.2%, and 0% while among the SR, they were 57.1%, 35.7%, and 7.14%, respectively. Our data show the unique presence of G/G genotype in the SR group (3 patients; 7.14%). Moreover, the "G" allele frequencies among chronic and resolved subjects were 12.6% and 25.0%, respectively (p=0.0136). Importantly, subjects with the GG genotype were more likely to clear their HCV infection than those with the AA genotype (p=0.0118). Conclusions: HCV genotype 4a subjects with the IL-27-p28.rs153109 A/G and G/G genotype were more likely to clear their HCV infection. Therefore, we propose IL- 27p28.rs153109SNPas a genetic biomarker for predicting HCV infection outcome.
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