Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways

BACKGROUND Allyl isothiocyanate(AITC),a classic anti-inflammatory and antitumorigenic agent,was recently identified as a potential treatment for obesity and insulin resistance.However,little is known about its direct impact on the liver.AIM To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease(commonly referred to as NAFLD).METHODS To establish a mouse and cellular model of NAFLD,C57BL/6 mice were fed a high fat diet(HFD)for 8 wk,and AML-12 cells were treated with 200μM palmitate acid for 24 h.For AITC treatment,mice were administered AITC(100 mg/kg/d)orally and AML-12 cells were treated with AITC(20μmol/L).RESULTS AITC significantly ameliorated HFD-induced weight gain,hepatic lipid accumulation and inflammation in vivo.Furthermore,serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice.Mechanistically,AITC significantly downregulated the protein levels of sterol regulatory elementbinding protein 1(SREBP1)and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acidβ-oxidation,as well as the upstream mediators Sirtuin 1(Sirt1)and AMPactivated protein kinaseα(AMPKα),in the livers of HFD-fed mice.AITC also attenuated the nuclear factor kappa B(NF-κB)signaling pathway.Consistently,AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways.Importantly,further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKαin AML-12 cells.CONCLUSION AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway.Therefore,AITC is a potential therapeutic agent for NAFLD.

Screening for pancreatic cancer in familial high-risk individuals: A systematic review

AIM:To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals(HRIs).METHODS:Studies were identified by searching PubMed,EBSCO,ClinicalTrials.gov and the Cochrane database from database inception to June 2014.We also obtained papers from the reference lists of pertinent studies and systematic reviews.Englishlanguage trials and observational studies were searched.The key words used as search terms were "screening" and "surveillance".Cost-effectiveness,diagnostic rate,survival rate,mortality and adverse events were the outcomes of interest.Age,sex,lifestyle and other confounding factors were also considered.However,anticipating only a few of these studies,we also included observational studies with or without control groups.We also included studies concerning the anxiety associated with pancreatic cancer risk and other psychological changes in familial HRIs.We extracted details on study design,objectives,population characteristics,inclusion criteria,year of enrollment,method of screening,adjusted and unadjusted mortality,cost-effectiveness and adverse events from the included studies.Studies were assessed using the Reporting of Observational studies in Epidemiology(STROBE) checklist.RESULTS:Sixteen studies on pancreatic cancer screening were included.Five studies included control groups,nine were observational studies without control groups,and the other two studies investigated the worry associated with pancreatic cancer risk.We found that pancreatic cancer screening resulted in a high curative resection rate(60%vs 25%,P = 0.011),longer median survival time(14.5 mo vs 4 mo,P < 0.001),and higher 3-year survival rate(20%vs 15.0%,P =0.624).We also found that familial HRIs had a higher diagnostic rate of pancreatic tumors than controls(34%vs 7.2%,P< 0.001).In patients who underwent regular physical examinations,more stage I pancreatic cancers were observed(19%vs 2.6%,P= 0.001).In addition,endoscopic ultrasonography,which was the main means of detection,diagnosed 64.3%of pancreatic cancers.In comparison,endoscopic retrograde cannulation of the pancreas,magnetic resonance imaging,and computed tomography diagnosed 28.6%,42.9%,and21.4%,respectively.For mass lesions,instant surgery was recommended because of the beneficial effects of post-operative chemotherapy.However,in patients with intraductal papillary mucinous neoplasms,we did not find a significant difference in outcome between surgery and follow-up without treatment.Moreover,pancreatic cancer screening in familial HRIs had a greater perceived risk of pancreatic cancer(P< 0.0001),higher levels of anxiety regarding pancreatic cancer(P< 0.0001),and increased economic burden.CONCLUSION:Pancreatic cancer screening in familial HRIs is associated with a higher detection rate and longer survival,although screening may influence psychological function and increase the economic burden.

Clinical guidelines of non-alcoholic fatty liver disease: A systematic review

AIM To perform a systematic review to grade guidelines and present recommendations for clinical management of non-alcoholic fatty liver disease(NAFLD).METHODS A database search was conducted on Pub Med for guidelines published before May 2016, supplemented by reviewing relevant websites. The Appraisal of Guidelines for Research and Evaluation(ARGEE) instrument Ⅱ was a tool designed to appraise the methodological rigor and transparency in which a clinical guideline is developed and it is used internationally. it was used to appraise the quality of guidelines in this study. The inclusion criteria include: clinical NAFLD guidelines for adults, published in English, and released by governmental agencies or key organizations.RESULTS Eleven guidelines were included in this study. Since 2007, guidelines have been released in Asia(3 in China, 1 in South Korea, and 1 in Japan), Europe(1 in italy),America(1 in United States and 1 in Chile) and three international agencies [European associations joint, Asia-Pacific Working Party and World Gastroenterology Organization(WGO)]. Using the ARGEE Ⅱ instrument, we found US 2012 and Europe 2016 had the highest scores, especially in the areas of rigor of development and applicability. Additionally, italy 2010 and Korea 2013 also presented comprehensive content, rigorous procedures and good applicability. And WGO 2014 offered various algorithms for clinical practice. Lastly, a practical algorithm for the clinical management was developed, based on the recommended guidelines.CONCLUSION This is the first systematic review of NAFLD guidelines. it may yield insights for physicians and policy-makers in the development and application of guidelines.

Association between serum alpha-fetoprotein levels and fatty liver disease: A cross-sectional study

AIM: To investigate the association between serum alpha-fetoprotein(AfP) levels and fatty liver disease(fLD) in a Chinese population.METHODS: A cross-sectional study was performed among subjects who presented for a health examination at the First Affiliated Hospital, College of Medicine, Zhejiang University in 2013. fLD was diagnosed based onan ultrasonography examination. Serum AfP levels were measured with a chemiluminescence immunoassay.RESULTS: Of the 9800 subjects enrolled, 2601 were diagnosed with fLD. Subjects with fLD had higher serum AfP levels than those without the disease. Subjects with high serum AfP levels had a higher prevalence of fLD, metabolic syndrome, and its components. Univariate logistic analysis showed that elevated serum AfP levels were associated with an increased risk of fLD(OR = 1.057, 95%CI: 1.031-1.084). however, after adjusting for covariates, AFP no longer remained significantly associated with the risk factors for fLD. CONCLUSION: Our results suggest that serum AfP levels are significantly associated with fLD and that AfP acts as a cofactor, but not as an independent factor, for fLD.