• BMB Reports
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• 제54권6호
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• pp.323-328
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• 2021

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.40-47
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• 2023

Activation of the NLRP3 inflammasome is a necessary process to induce fibrosis in nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is a kind of NAFLD that encompasses the spectrum of liver disease. It is characterized by inflammation and ballooning of hepatocytes during steatosis. We tested whether inhibiting the NLRP3 inflammasome could prevent the development and pathology of NASH. We identified loganin as an inhibitor of the NLRP3 inflammasome and investigated whether in vivo administration of loganin prevented NASH symptoms using a methionine-choline deficient (MCD) diet model in mice. We found that loganin inhibited the NLRP3 inflammasome activation triggered by ATP or nigericin, as shown by suppression of the production of interleukin (IL)-1β and caspase-1 (p10) in mouse primary macrophages. The speck formation of apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC) was blocked by loganin, showing that the assembly of the NLRP3 inflammasome complex was impaired by loganin. Administration of loganin reduced the clinical signs of NASH in mice fed the MCD diet, including hepatic inflammation, fat accumulation, and fibrosis. In addition, loganin reduced the expression of NLRP3 inflammasome components in the liver. Our findings indicate that loganin alleviates the inflammatory symptoms associated with NASH, presumably by inhibiting NLRP3 inflammasome activation. In summary, these findings imply that loganin may be a novel nutritional and therapeutic treatment for NASH-related inflammation.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3697-3703
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• 2016

Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sorafnib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권2호
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• pp.204-209
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• 2008

저자들은 뇌하수체저하증을 동반한 조기에 발병된 소아 비만 환자에서 비알코올성 지방간질환의 진행으로 인한 간경화를 경험하였기에 이를 보고하는 바이며, 향후 뇌하수체저하증이 동반된 비만 환자에서 비알코올성 지방간질환의 발생 및 진행에 대한 주의 깊은 관찰이 필요할 것으로 사료된다.

• Clinical and Experimental Pediatrics
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• 제52권11호
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• pp.1279-1282
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• 2009

당뇨병 환자에서 간비대와 간 기능 이상이 동반될 경우 간 내 당원축적증과 비알콜성 지방간염을 감별해야 한다. 저자들은 인슐린 치료를 제대로 받지 않아 혈당 조절이 불량한 환자에서 저혈당과 간비대로 발현한 간 내 당원축적증을 경험하여 보고한다. 만 6세경 1형 당뇨병으로 진단받은 환아로 10세경 우상복부 통증과 반복되는 고혈당과 저혈당으로 내원하였으며, 당시 진찰상 둥근 얼굴, 우측 늑골연 하방 6 cm 정도에서 만져지는 간비대가 있었다. 검사상 소변 케톤 양성, 당화혈색소는 9.6%였다. 간 효소치가 증가되어 있었고, 혈중 콜레스테롤/중성지방 250/267 mg/dL였다. 바이러스성 간염, 자가면역성 간염, 대사성 간 질환에 대한 검사는 모두 정상이었다. 복부 초음파 및 컴퓨터 단층 촬영상 지방간과 간비대 소견을 보였다. 간 조직 검사상 PAS 염색에서 양성, diastase-PAS 염색에서는 음성으로 전형적인 당원축적증의 소견을 보였다. 고혈당을 보일 때마다 초속효성 인슐린을 투여하고 심한 저혈당의 증상이 동반된 경우 글루카곤을 투여하였으며 생옥수수 전분 가루를 간식으로 먹이면서 저혈당 횟수가 감소하여 퇴원하였다. 현재 외래에서 초속효성 인슐린으로 혈당 조절하면서 관찰 중이다. 제1형 당뇨병 환자에서 당원축적증은 간비대와 간 효소치의 상승을 야기할 수 있는 원인이다. 본 증례에서는 심한 저혈당이 반복되어 하루에도 수 차례 글루카곤을 투여하였으며, 생옥수수 전분 가루을 투여하면서 저혈당이 호전되었다. 엄격한 혈당 관리로 간 비대 및 간 기능 이상이 호전될 수 있으므로 적절한 인슐린 치료로 혈당을 조절하고 저혈당을 예방해야 하겠다.

• Clinical and Experimental Pediatrics
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• 제50권8호
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• pp.794-798
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• 2007

간-폐 증후군이란 진행된 간경변을 가진 환자에서 폐혈관의 확장으로 인해 동맥혈 산소 포화도가 감소하는 것을 특징으로 한다. 간경화 환자에서 동맥 산소 포화도의 감소가 보고된 이후로 간-폐 증후군은 말기 간질환을 가진 성인의 13-47% 정도에서 발생한다고 보고하고 있으나, 소아에서 발생한 국내 보고는 없다. 또한 시상하부 및 뇌하수체 기능 저하를 보이는 환자에서 비알코올성 지방간이 급격하게 간부전으로 진행되는 증례가 최근에 보고되고 있다. 저자들은 지방간을 가진 소아에서 두개인두종 절제술 후에 발생한 뇌하수체기능저하증으로 인해 간질환이 급격하게 진행하여 간-폐 증후군으로 발현된 증례를 경험하였기에 보고하는 바이다. 두부 수술 후에 시상하부 및 뇌하수체 기능 저하를 보이는 환아에서는 내분비 질환이나 대사 장애 뿐 아니라, 간질환에 대한 추적 관찰이 필요할 것이다.

• 한국건강관리협회지
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• 제3권2호
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• pp.121-136
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• 2005

Background/Aims The liver funtion tests(LFTs), such as aspartate aminotransferase(AST), alanine amino-transferase(ALT), r -glutamyl transferase( r -GT), have been widely used for screening tests but their low positive predictive value can cause many false positive results. To evaluate the clinical usefulness of these tests, we analyzed serial LFT results of single factory workers and compared the risk factor's in groups divided by the serial LFT results. Methods From June 2001 to October 2001, 1223 consecutive healthy workers in a single factory were enrolled and questionnaire, LFT and liver ultrasonography were performed. Previous LFT results were collected from Annual Health Examination Survey. According to the abnormalities in serial LFT, participants were classified into three groups (abnormal-in-both, alternating normal-in-both) and the risk factors were compared among these groups using multiple logistic regression Results The prevalence of LFT abnormality in a single test was 16.8% but, in serial LFT, only 5% of participants showed consistent abnormality. The risk factors for abnormal-in-both group, compared with alternating group, were liver ultrasonography abnormality such as fatty liver(odds ratio, 2.2; p=0.026) and heavy alcohol intake (more than 210g/week) (odds ratio, 7.2;P=0.064). HBsAg was not significant risk factor for any of the three groups. ConclusionIn factory workers with serial LFT abnormality, alcoholic liver disease could be the principal cause of abnormal LFT. Even if HBsAg were positive in patients with abnormal LFT, there is a possibility of another causes for LFT abnormalities such as alcoholic liver disease and nonalcoholic steatosis or steatohepatitis

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제22권5호
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• pp.470-478
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• 2019

Purpose: The incidence of non-alcoholic fatty liver disease (NAFLD) in children is gradually increasing. The aim of this study was to investigate the use of serum adiponectin and soluble adiponectin receptor 2 (soluble Adipo R2) levels for the diagnosis of fatty liver disease in obese and overweight children. Methods: The study included 51 obese and overweight children between the ages of 6 and 18 years diagnosed with NAFLD using ultrasonography and 20 children without fatty liver disease. Patients whose alanine transaminase level was two times higher than normal (${\geq}80U/L$) were included in the non-alcoholic steatohepatitis (NASH) group. Results: NASH was observed in 11 (21.6%) of the patients with NAFLD. The incidence of obesity was higher in patients with NASH (80% and 45%, p=0.021). While the adiponectin levels were similar in patients with NAFLD and those without, they were below the normal level in the whole study group. Adiponectin and soluble Adipo R2 levels of patients with NASH were lower than those in patients without NASH; however, this difference was not statistically significant (p=0.064 and p=0.463). Soluble Adipo R2 levels in obese patients with NAFLD were higher than those in obese children without NAFLD (p<0.001). Conclusion: Soluble adiponectin receptor 2 level is a noninvasive marker that can be used for the diagnosis of NAFLD in obese children.

• Nutrition Research and Practice
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• 제17권1호
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• pp.13-31
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• 2023

BACKGROUND/OBJECTIVES: Epigenetic regulation by nutrients can influence the development of specific diseases. This study sought to examine the effect of individual nutrients and nutrient families in the context of preventing chronic metabolic diseases via epigenetic regulation. The inhibition of lipid accumulation and inflammation by nutrients including proteins, lipids, vitamins, and minerals were observed, and histone acetylation by histone acetyltransferase (HAT) was measured. Correlative analyses were also performed. MATERIALS/METHODS: Nutrients were selected according to information from the Korean Ministry of Food and Drug Safety. Selected nutrient functionalities, including the attenuation of fatty acid-induced lipid accumulation and lipopolysaccharide-mediated acute inflammation were evaluated in mouse macrophage Raw264.7 and mouse hepatocyte AML-12 cells. Effects of the selected nutrients on in vitro HAT inhibition were also evaluated. RESULTS: Nitric oxide (NO) production correlated with HAT activity, which was regulated by the amino acids group, suggesting that amino acids potentially contribute to the attenuation of NO production via the inhibition of HAT activity. Unsaturated fatty acids tended to attenuate inflammation by inhibiting NO production, which may be attributable to the inhibition of in vitro HAT activity. In contrast to water-soluble vitamins, the lipid-soluble vitamins significantly decreased NO production. Water- and lipid-soluble vitamins both exhibited significant inhibitory activities against HAT. In addition, calcium and manganese significantly inhibited lipid accumulation, NO production, and HAT activity. CONCLUSIONS: Several candidate nutrients and their family members may have roles in the prevention of diseases, including hepatic steatosis and inflammation-related diseases (i.e., nonalcoholic steatohepatitis) via epigenetic regulation. Further studies are warranted to determine which specific amino acids, unsaturated fatty acids and lipid-soluble vitamins or specific minerals influence the development of steatosis and inflammatory-related diseases.

• Clinical and Experimental Pediatrics
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• 제49권10호
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• pp.1037-1041
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• 2006

목 적 : 소아에서 비만 유병률 증가와 함께 비알콜성 지방간염도 증가하고 있다. 본 연구에서는 청소년에서 혈청 아미노 전이 효소 상승 빈도를 조사하고 체지방 분포 및 혈청 인슐린 농도와의 관계를 알아보고자 한다. 방 법 : 3,636명을 대상으로 하였고 이들의 평균 연령은 $15.7{\pm}0.7$세였다. 대상자로부터 신장, 체중, 허리둘레, 둔위를 측정하고 혈액검사를 통하여 AST, ALT및 공복시 인슐린을 측정하였다. 비만 및 과체중군은 성별, 연령별 체질량지수와 비교하여 각각 95 백분위수 이상, 85-94 백분위수로 정의하였다. 결 과 : 비만군은 324명으로 8.9%였으며 과체중군은 414명(11.4%)이었다. 허리둘레와 둔위 및 허리-둔위비는 남녀학생 모두에서 각 군간에 유의한 차이를 보였다. ALT 평균치는 각 군간에 유의한 차이를 보였다(비만군 : $32.1{\pm}34.3U/L$, 과체중 : $19.6{\pm}13.6U/L$, 대조군 : $12.7{\pm}6.7U/L$, P<0.001). AST 평균치 또한 각 군별로 유의한 차이를 보였다(비만군 : $27.8{\pm}16.5U/L$, 과체중군 : $22.8{\pm}8.6U/L$, 대조군 : $20.8{\pm}8.5U/L$, P<0.001). AST 및 ALT는 체질량지수, 허리둘레, 둔위, 허리-둔위비 및 혈청 인슐린 농도와 각각 유의한 상관 관계를 가졌다. 다중회귀분석결과 여러 신체 계측치와 인슐린 농도 중에서 ALT와 유의한 상관 관계를 갖는 것은 허리둘레, 체질량지수, 인슐린 농도 였으며(r=0.435, P<0.001), AST에 영향을 주는 인자는 허리둘레였다(r=0.234, P<0.001). 결 론 : 비만군 및 과체중군에서 혈청 아미노 전이 효소 증가대상자의 비율이 의미 있게 증가되어 있었고 허리둘레는 AST 및 ALT 증가를 예측하는데 유용한 지표로 사용될 수 있다.