Investigating fatty liver disease-associated adverse outcome pathways of perfluorooctane sulfonate using a systems toxicology approach.

Adverse outcome pathway (AOP) frameworks help elucidate toxic mechanisms and support chemical regulation. AOPs link a molecular initiating event (MIE), key events (KEs), and an adverse outcome by key event relationships (KERs), which assess the biological plausibility, essentiality, and empirical evidence involved. Perfluorooctane sulfonate (PFOS), a hazardous poly-fluoroalkyl substance, demonstrates hepatotoxicity in rodents. PFOS may induce fatty liver disease (FLD) in humans; however, the underlying mechanism remains unclear. In this study, we evaluated the toxic mechanisms of PFOS-associated FLD by developing an AOP using publicly available data. We identified MIE and KEs by performing GO enrichment analysis on PFOS- and FLD-associated target genes collected from public databases. The MIEs and KEs were then prioritized by PFOS-gene-phenotype-FLD networks, AOP-helpFinder, and KEGG pathway analyses. Following a comprehensive literature review, an AOP was then developed. Finally, six KEs for the AOP of FLD were identified. This AOP indicated that toxicological processes initiated by SIRT1 inhibition led to SREBP-1c activation, de novo fatty acid synthesis, and fatty acid and triglyceride accumulation, culminating in liver steatosis. Our study provides insights into the toxic mechanism of PFOS-induced FLD and suggests approaches to assessing the risk of toxic chemicals.

Signal detection of human papillomavirus vaccines using the Korea Adverse Events Reporting System database, between 2005 and 2016.

Background Adverse events (AEs) not listed on drug labels have recently been reported in young girls vaccinated against HPV, but signal detection related to the human papillomavirus (HPV) vaccine has never been conducted in South Korea using the Korea Adverse Event Reporting System database of Korea Institute of Drug Safety & Risk Management at Ministry of Food and Drug Safety. Objective To analyze signals associated with HPV vaccines using the Korean spontaneous AEs reporting system and data-mining methods and compare the results to current vaccine label information in South Korea and the United States of America, United Kingdom, European Union, and Japan to detect signals not currently listed on the labels. Setting We evaluated the Korea Institute of Drug Safety & Risk Management database from January 2005 to December 2016. After pre-screening the data, the adjusted total numbers of HPV-related AE reports and AEs were 2566 and 4748 and those of all other vaccine-related AE reports and AEs were 21,878 and 120,688, respectively. Methods Three data mining algorithms (proportional reporting ratio, reporting odds ratio and information component) were used to assess AEs. A signal was defined when the criteria for all three indicators were satisfied. The detected signals were compared to the label information of HPV vaccines from South Korea, the United States of America, United Kingdom, European Union, and Japan. Main outcome measure Signals of AE after HPV vaccination, which met all three data mining indices. Results In this study, we found a total 97 signals of AE after HPV vaccination. Of these, 78 AEs were already present on the HPV vaccine labels of South Korea and the following 19 AEs were not listed: neuralgia, tremor, neuritis, depersonalization, axillary pain, personality disorder, increased salivation, peptic ulcer, circulatory failure, hypotension, peripheral ischemia, cerebral hemorrhage, micturition disorder, facial edema, ovarian cyst, weight increase, pain anxiety, oral edema, and back pain. Moreover, AE information on the current HPV vaccine labels of South Korea, the United States of America, United Kingdom, European Union, and Japan was inconsistent. When comparing the 19 AE signals that were not listed on the drug label in South Korea with the labels from the other countries, neuritis, axillary pain, cerebral hemorrhage, facial edema, pain anxiety, and back pain appreared on the U.S. Food and Drug Administration HPV vaccine labels but not on the United Kingdom labels, and hypotension was listed only on labels in the European Union and Japan. Conclusions South Korea should develop a system for proactively updating HPV labels. These results also suggest potential research directions such as vaccination label expansion, pharmacovigilance studies, and identification of causality in AEs associated with HPV vaccination.

The use of complementary and alternative medicine in a general population in South Korea: results from a national survey in 2006.

The purpose of this survey was to obtain information on the prevalence, costs, and patterns of use of complementary and alternative medicine (CAM) in a general population in the Republic of Korea. In 2006, we conducted nationwide and population-weighted personal interviews with 6,021 adults ranging from 30 to 69 yr of age; the final sample consisted of 3,000 people with a 49.8% response rate. In addition to their general socio-demographics, the respondents were asked about their use of CAM during the previous 12-month period, costs, sources of information, and reasons for use. The prevalence of use overall was 74.8%, while biologically based CAM therapies were the most likely type of use (65.4%). The median annual out-of-pocket expenditures for CAM therapies was about US$203. The primary reason for using CAM was for disease prevention and health promotion (78.8%). The main source of advice about CAM therapies use was most likely to be from family and friends (66.9%). Our study suggests that CAM use has been and continues to be very popular in South Korea. Conventional western medical doctors and governments should obtain more evidence and become more interested in CAM therapies.