• Journal of Korean Medical Science
• /
• v.33 no.52
• /
• pp.335.1-335.17
• /
• 2018

Background: Spontaneous bacterial peritonitis (SBP) is a serious infectious complication in patients with liver cirrhosis. However, information about prognosis of SBP in hepatocellular carcinoma (HCC) patients is limited. We investigated the clinical course of SBP in HCC patients. Methods: This study enrolled patients diagnosed with SBP between 2005 and 2017. Medical records of patients were reviewed and clinical course was compared between the non-HCC and HCC groups. Results: In total, 123 SBP cases including 49 HCC cases were enrolled. Men were predominant (48/74, 64.9% vs. 34/49, 69.4%; P = 0.697); median age was 58 years in both non-HCC and HCC groups (P = 0.887). The most common etiology was alcohol (32/74, 43.2%) in non-HCC group and hepatitis B (30/49, 61.2%) in HCC group (P = 0.009). Antibiotic resistance rate was higher in non-HCC than in HCC group (29.7% vs. 12.2%; P = 0.028); in-hospital mortality did not differ between the groups (25/74, 33.8% vs. 13/49, 26.5%; P = 0.431). Development rate of hepatorenal syndrome did not differ between non-HCC and HCC group (14/74, 18.9% vs. 10/49, 20.4%; P = 1.000), but hepatic encephalopathy was less common in HCC group (26/74, 35.2% vs. 9/49, 18.3%; P = 0.008). The most important predictor of in-hospital mortality in patients with HCC was white blood cell count above $11,570cells/mm^3$ (odds ratio, 6.629; 95% confidence interval, 1.652-26.590; P = 0.008). Conclusion: Prognosis of SBP in HCC patients is relatively less severe. This result may be related with reduced antibiotics resistance and lower development rates of other complications, such as hepatic encephalopathy. Degree of systemic inflammation may be the most important factor for in-hospital mortality.

• YAKHAK HOEJI
• /
• v.42 no.1
• /
• pp.82-88
• /
• 1998

The effect of hepatoprotective agents and bile acids on tumor necrosis factor-alpha, (TNF-${\alpha}$) production in murine and human macrophage cell line (RAW264.7 and U937) was inve stigated. The hepatoprotective agents including silymarin and its major component, silybin, significantly inhibited TNF-alpha production in a concentration dependent manner ($IC_50$ of silybin=67.7${\mu}g$/ml (140.3${\mu}g$M)). In differentiated U937 cells, especially, silybin showed more effective inbitory activity ($IC_50$=35.1${\mu}g$g/ml (72.7${\mu}g$M)). These results suggest that silymarin and silybin may inhibit TNF-alpha production in the process of hepatic diseases in human. However, biphenyldimethyl dicarboxylate (DDB) was not effective. In the case of bile acids, chenodeoxycholic acid (CDCA) showed a concentration dependent inhibitory effect on TNF-alpha production ($IC_50$ of CDCA= 71.5${\mu}g$g/ml (182.1${\mu}g$M)). In contrast, glycine or taurine conjugated form (G-CDCA or T-CDCA) restored to the control level or significantly increased TNF-${\alpha}$ production. And also ursodeoxycholic acid (UDCA) and its conjugated forms (G-UDCA and T-UDCA) showed a variety of patterns on TNF-${\alpha}$ production by changes of functional groups and concentration. These results also indicate that bile acids may regulate TNF-${\alpha}$ production in normal hepatic function or disease conditions.

• Nutrition Research and Practice
• /
• v.13 no.1
• /
• pp.3-10
• /
• 2019

BACKGROUND/OBJECTIVES: The $NAD^+$ precursor nicotinamide riboside (NR) is a type of vitamin $B_3$ found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; $250{\mu}M$) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR ($10{\mu}M$ and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.

• Nutrition Research and Practice
• /
• v.12 no.6
• /
• pp.535-540
• /
• 2018

BACKGROUND/OBJECTIVES: Propolis has a rich source of bioactive compounds and has renal and hepatic protective properties. The purpose of this study was to investigate the beneficial effect of hydro-ethanolic extract of propolis against paracetamol-induced liver damage and impairment of kidney function, as well as hematological changes in rats. MATERIALS/METHODS: Six groups of rats were used; the first group was served as a control; the second and third groups were treated by propolis extract at a dose of 50 and 100 mg/kg.B.WT. respectively; the fourth group was treated by paracetamol (200 mg/kg.B.WT.); the fifth group was treated by propolis (50 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days; and the sixth group was treated with propolis (100 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days. All the animals were treated for a period of 15 days. At the end of the experimental period, blood samples were collected for measurement of the liver enzymes, serum albumin, protein and creatinine, blood urea nitrogen, hematological parameters, and urine volume, protein and albumin. RESULTS: Paracetamol over dose significantly lowered hemoglobin, serum total protein, albumin, and uric acid, while it significantly increased blood creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, white blood cells, and platelet count as compared to the control. However, these alterations were significantly attenuated by the use of propolis extract and the effect was dose dependent. Interestingly, propolis prevented paracetamol induced proteinuria, low hemoglobin and body weight loss. CONCLUSIONS: Propolis significantly prevented paracetamol induced renal, hepatic and hematological toxicity and might be useful in the management of liver and renal diseases particularly proteinuria.

• BMB Reports
• /
• v.54 no.9
• /
• pp.476-481
• /
• 2021

Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism in maintaining a normal liver physiological state during fasting. The Lrh-1^f/f and LRH-1 liver-specific knockout (Lrh-1^LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. The livers were used for qPCR, western blot, and histological analysis. Primary hepatocytes were isolated for immunocytochemistry assessments of lipids. During fasting, the Lrh-1^LKO mice showed increased accumulation of triglycerides in the liver compared to that in Lrh-1^f/f mice. Interestingly, in the Lrh-1^LKO liver, decreases in perilipin 5 (PLIN5) expression and genes involved in β-oxidation were observed. In addition, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed us to analyze the Plin5 promoter sequence, which revealed -1620/-1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immunoprecipitation assays. Additionally, fasted Lrh-1^f/f primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted Lrh-1^LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs, protect the liver from lipid overload, and manage the cellular needs during fasting.

• Molecules and Cells
• /
• v.45 no.4
• /
• pp.180-192
• /
• 2022

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.

• Journal of Acupuncture Research
• /
• v.24 no.3
• /
• pp.145-161
• /
• 2007

Objectives : The purpose of this study is to investigate the effect of electroacupuncture at Joksanmi($ST_{36}$) on Rat's aging by experimental methods. Methods : The author performed several experimental procedures to observe the effects of the EC-HAS at the arthritis. First, I measured the cell survival rate of the mice lung fibroblasts. Second, the incidence rate of arthritis and arthritis index of CIA were analyzed. Third, the levels of IL-6, $INF-{\gamma}$ , $INF-{\alpha}$ , $IL-1{\beta}$, IgG, IgM and anti-collagen II were measured in serum and the level of $INF-{\gamma}$, $INF-{\gamma}$/IL-4 ratio in the CIA mouse spleen cell culture. Fourth, histological analysis of the mice joint was performed. Fifth, the expression ratio of $CD3e^+$ cells to $CD19^+$ cells, $CD4^+$ cells to $CD8^+$ cells, $CD11a^+CD19^+$ cells, $CD4^+CD25^+$ cells, $CD3^+CD69^+$ cells, and $CD11b^+Gr-1^+$ cells were checked. Results: 1. The hematocrit was meaningfully (p<0.01, p<0.05) decreased in $ST_{36}$ group in comparison with the control and sham group. 2. The glucose, ALP were meaningfully (p<0.05, p<0.05) decreased in $ST_{36}$ group in comparison with the control group. 3. In the activation of hepatic antioxidase, the catalase was meaningfully (p<0.01) increased in $ST_{36}$ group in comparison with the control group. 4. In the liver, the NO formation was meaningfully (p<0.001) decreased in $ST_{36}$ group in comparison with the nomal, control and sham group. 5. In the activation of splenetic antioxidase, the GSH was meaningfully (p<0.01) increased in $ST_{36}$ group in comparison with the sham group, and the catalase was meaningfully (p<0.001) increased in $ST_{36}$ group in comparison with the control group. 6. In the spleen, the MDA formation was meaningfully (p<0.01, p<0.05) decreased in $ST_{36}$ group in comparison with the control and sham group. 7. In the spleen cell culture, the levels of IL-6 was meaningfully (p<0.05) decreased in comparison with the sham group, $INF-{\gamma}$( was meaningfully (p<0.05) increased in comparison with the control group. Conclusions: According to the results, it is considered that electroacupuncture at Joksamni($ST_{36}$) is effective in increasing the activities of antioxidative enzyme and inhibiting lipid peroxides, and has an immunomodulatory reaction. In conclusion, it han an significant anti-aging effect and need more experimental study.

• The Journal of Pediatrics of Korean Medicine
• /
• v.30 no.2
• /
• pp.31-46
• /
• 2016

Objectives In this study, the effects of Ja-eum-gang-hwa-tang (JGT) on the increase in airway epithelial mucosubstances of rats and ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Materials and Methods Hypersecretion of airway mucus was produced by exposure of $SO_2$ to rats for 3 weeks. The effect of orally-administered JGT for 2 weeks on increased epithelial mucosubstances from tracheal goblet cells of rats was assessed by using histopathological analysis after staining the epithelial tissue with Hematoxylin-eosin and PAS-alcian blue. Possible cytotoxicity of JGT was assessed by investigating the potential damage on kidneys and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment. Also, the effect of JGT on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of JGT and treated with ATP ($200{\mu}M$) or PMA ($10ng/ml$) or EGF ($25ng/ml$) or TNF-${\alpha}$ (0.2 nM) for 24 hrs to assess the effect of JGT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results (1) JGT decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) JGT did not show any renal and hepatic toxicities, and did not affect body weights either. (3) JGT significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) JGT inhibited EGF-, and PMA-induced expression levels of MUC5AC gene in NCI-H292 cells. However, ATP- and TNF-${\alpha}$-induced MUC5AC gene expression levels were not affected in NCI-H292 cells. Conclusions The result from the present study suggests that JGT might control the production and gene expression of airway mucin observed in various respiratory diseases which accompanied by mucus hypersecretion. Also, JGT did not show liver toxicity or impact on kidney functions. The effect of JGT should be further studied by using animal experimental models which can show proper pathophysiology of airway diseases.

• Nutrition Research and Practice
• /
• v.15 no.3
• /
• pp.294-308
• /
• 2021

BACKGROUD/OBJECTIVES: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells. MATERIALS/METHODS: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively. RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

• The Korean Journal of Nuclear Medicine
• /
• v.37 no.6
• /
• pp.418-427
• /
• 2003

Objects: $^{99m}-lactosylated$ human serum albumin (LSA) is a newly synthesized radiopharmaceutical that binds to asialoglycoprotein receptors, which are specifically presented on the hepatocyte membrane. Hepatic uptake and blood clearance of LSA were evaluated in rat with acute hepatic injury induced by dimethylnitrosamine (DMN) and results were compared with corresponding findings of liver enzyme profile and these of histologic changes. Materials and Methods: DMN (27 mg/kg) was injected intraperitoneally in Sprague-Dawley rat to induce acute hepatic injury. At 3(DMN-3), 8(DMN-8), and 21 (DMN-21) days after injection of DMN, LSA injected intravenously, and dynamic images of the liver and heart were recorded for 30 minutes. Time-activity curves of the heart and liver were generated from regions of interest drawn over liver and heart area. Degree of hepatic uptake and blood clearance of LSA were evaluated with visual interpretation and semiquantitative analysis using parameters (receptor index : LHL3 and index of blood clearance : HH3), analysis of time-activity curve was also performed with curve fitting using Prism program. Results: Visual assessment of LSA images revealed decreased hepatic uptake in DMN treated rat, compared to control group. In semiquantitative analysis, LHL3 was significantly lower in DMN treated rat group than control rat group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p<0.05), whereas HH3 was significantly higher than control rat group (DMN-3: 0.731,.DMN-8: 0.654, DMN-21: 0.604, Control: 0.473, p<0.05). AST and ALT were significantly higher in DMN-3 group than those of control group. Centrilobular necrosis and infiltration of inflammatory cells were most prominent in DMN-3 group, and were decreased over time. Conclusion: The degree of hepatic uptake of LSA was inversely correlated with liver transaminase and degree of histologic liver injury in rat with acute hepatic injury.