Ministry of Food and Drug Safety

Abstract Background Yersinia enterocolitica is a psychrotrophic foodborne bacterium capable of growing at refrigeration temperatures and is frequently associated with animal-source foods, raising concerns for food safety and public health. Despite its relevance and the increasing use of whole-genome sequencing (WGS) for bacterial surveillance, genomic studies on Y. enterocolitica isolates from South Korea are limited. In this study, we analyzed 157 Y. enterocolitica isolates obtained from pork, beef, chicken, and duck collected nationwide using WGS to elucidate their genomic diversity and adaptive features. Results Phylogenomic analysis classified all isolates as biotype 1A (sub-biotype 1Aa) and revealed considerable genetic heterogeneity, comprising 40 sequence types (STs) and 66 core-genome types (CTs). No clear segregation by source was observed, suggesting cross-source circulation within livestock production and processing environments. Pan-genome analysis identified 23,110 gene clusters, revealing an open pan-genome enriched in genes associated with metabolism, defense mechanisms, and stress responses, reflecting high genomic flexibility. Although the canonical virulence plasmid pYV was absent, we identified a conserved set of chromosomal virulence-associated genes linked to adhesion ( inv , yapE ), secretion, and enterotoxicity ( ystB ), suggesting enhanced potential for persistence rather than pronounced pathogenicity. Antimicrobial resistance (AMR) genes were predominantly intrinsic, including blaA (β-lactamase) and vat(F) (streptogramin resistance), which were universally detected, whereas acquired AMR genes such as tet(C) and ant(3'')-Ia were sporadically observed. Furthermore, approximately one-third of isolates harbored Col- and Inc-type plasmid replicons, supporting the occurrence of horizontal gene exchange and environmental adaptation. Conclusions Y. enterocolitica from animal-source foods in South Korea represents a genetically diverse and environmentally resilient population with limited virulence and predominantly intrinsic AMR determinants. These findings establish a genomic framework for understanding the ecology of Y. enterocolitica in animal-source foods and underscore the need for ongoing genomic surveillance to detect emerging variants that may influence food safety and public health.

This protocol paper describes the design and methodology of the Korean Human Exposure Safety Survey (KoHESS), a three-year national biomonitoring program (2023-2025). Korea's Act on Risk Assessment of Products for Human Use necessitates scientific evidence for aggregate exposure assessment and cumulative risk evaluation of hazardous substances in food and consumer products. Existing biomonitoring programs primarily focus on environmental exposures, limiting comprehensive assessment of products regulated by the Ministry of Food and Drug Safety. KoHESS employs repeated cross-sectional surveys targeting approximately 5,000 Koreans aged 3-79 years per cycle, using complex stratified multistage sampling for national representativeness. Data collection includes standardized anthropometric measurements, biological samples (blood, urine), comprehensive exposure source surveys, and 2-day 24-hour dietary recalls. Chemical analyses using liquid chromatography-tandem mass spectrometry and inductively coupled plasma mass spectrometry measure 24 perfluoroalkyl and polyfluoroalkyl substances compounds, 25 phthalate metabolites, and 7 heavy metals, with quality assurance through certified reference materials. KoHESS will provide scientifically robust data for establishing safety standards, enable advanced exposure modeling, facilitate risk assessments reflecting cumulative exposures, support targeted protection for vulnerable populations, and contribute to international biomonitoring networks while promoting preventive hazardous substance management systems.

Metabolic dysfunction-associated steatohepatitis (MASH) is associated with the activation of Kupffer cells (KCs) and hepatic stellate cells, at which point a metabolically stressed hepatocyte becomes integral to the progression of the disease. We observed a significant reduction in the level of alpha-1-antitrypsin (A1AT), a hepatocyte-derived secreted factor, in both patients with MASH and mice fed a fast-food diet (FFD). KC-mediated hepatic inflammation, most notably IL-1β, led to the transcriptional inhibition of A1AT by HNF4α. In quintuple Serpina1a–e knockout mice, ablation of A1AT worsened MASH through increased activity of proteinase 3 (PR3), a proinflammatory protease produced by F4/80hi/CD11blow/TIM4−/CCR2+ monocyte-derived KCs (MoKCs). Conversely, A1AT restoration or PR3 inhibition mitigated MASH progression. A PR3-bound cytokine array identified IL-32 as a key factor associated with MASH. Combining IL-32 with SERPINA1, the gene encoding A1AT, synergistically predicted patients at risk of MASH through univariate logistic regression analysis. Furthermore, in vivo overexpression of IL-32γ alleviated MASH induced by FFD. However, additional knockout of A1AT increased PR3 activity, consequently abolishing the anti-MASH effects of IL-32γ. Blocking PR3-mediated IL-32γ cleavage via the V104A mutation sustained its protective actions, while the PR3-cleaved C-terminal fragment activated KCs. Additionally, after cleavage, the antifibrogenic effect of IL-32γ is lost, resulting in a failure to prevent the activation of hepatic stellate cells. This study highlights the critical role of hepatocyte-derived A1AT in the PR3/IL-32γ axis during MASH development. Strategies to correct A1AT dysregulation, such as A1AT supplementation or PR3 inhibition with sivelestat, may offer protection against the development and progression of MASH and fibrosis.Elevated hepatic IL-1β levels in MASH lead to the downregulation of A1AT via the transcription factor HNF4α, resulting in increased recruitment of proinflammatory MoKCs and heightened PR3 activity. PR3 cleaves IL-32γ, transforming it from an anti-inflammatory and antifibrogenic cytokine into a potent activator of KCs and failing to prevent HSC activation. This cascade amplifies liver inflammation and fibrosis, suggesting that targeting the A1AT/PR3/IL-32γ axis could be a strategy for treating MASH.

Abstract So-called big data are potentially useful in the healthcare field and are of interest to researchers, industry, and government agencies. Over the past 10 years, Europe, the United States, and Asia have been making efforts to collect and systematically manage information on the entire process from clinical trials to follow-up management of medical devices (MD). We developed MD lifecycle research database at the Ministry of Food and Drug Safety (MFDS) of the Republic of Korea, consisting of 61 tables and 2,053 variables. The MFDS possesses statistical information on all MD, pharmaceuticals, foods, and human tissues produced and distributed. The information in the database is categorized according to four MD lifecycle phases-clinical trial, approval, production, and post-approval. For the clinical trial phase, the database contains information on planning and approval of clinical trial and non-clinical trial. The approval phase includes information on models, raw materials, quality, and changes, while the production phase stores information on production, import, export, supply and use. For the last step, follow-up management phase, provide information on post-marketing safety management, risk management, and administrative disposition. All four steps are linked based on primary key, so it is possible to understand information on the overall MD lifecycle. The MD Lifecycle Research Database will help strengthen the industry’s competitiveness in terms of cost-effectiveness in MD development and facilitate policy monitoring by improving its utilization in the public interest. This database contains information on all MD produced and distributed in Korea depending on the phases of the MD lifecycle, and data is easily accessible due to the lack risk of personal information exposure, so it can be widely used by individual researchers, industries, academia, and governments. Funding This research was supported by a grant (22063MFDS498) from ministry of food and drug safety in 2024. Key messages • We developed a medical device lifecycle database that enables tracking management according to the medical device lifecycle. • This database can be used as a scientific basis to ensure the safety, effectiveness, and efficiency of medical devices.

Neovascular age-related macular degeneration (nAMD) is characterized by abnormal blood vessel growth from the choroid, leading to complications and eventual blindness. Despite anti-VEGF therapy, subretinal fibrosis remains a major concern, as VEGF/VEGF receptor-2 (VEGFR2) signaling can contribute to both angiogenesis and fibrosis. For the identification of the aqueous humor proteome, we performed liquid chromatography with tandem mass spectrometry analysis. To investigate the potential therapeutic effects of targeting the VEGF signaling pathway using apatinib, a highly selective VEGFR2 tyrosine kinase inhibitor, this study employed in vitro (THP-1 conditioned media-treated ARPE-19 cells) and in vivo (laser-induced choroidal neovascularization mouse) models of nAMD. This study revealed elevated VEGFR2 protein levels in the aqueous humor of nAMD patients, suggesting a potential target to mitigate neovascularization and fibrosis in nAMD. Apatinib effectively reduced VEGFA and αSMA levels in both in vitro and in vivo models. Moreover, apatinib showed improvement in laser-induced subretinal hyper-reflective lesions. The action mechanism was linked to the inhibition of VEGFR2 activation, leading to the suppression of both angiogenesis and fibrosis through the downregulation of STAT3 phosphorylation. Therefore, the VEGFR2 signaling pathway appears to play a central role in the development of nAMD by regulating both angiogenesis and fibrosis.

The number of available drugs for treating aquatic animals is insufficient, given the occurrence of a variety of parasites and difficulties in developing appropriate treatments, such as vaccines or immunostimulants. Consequently, repurposing livestock drugs for treating aquatic animals is a viable alternative. Several studies have demonstrated that albendazole (ABZ) is a good anthelmintic for humans and animals such as ruminants, poultry, and honeybees. Therefore, we investigated the toxicological studies, metabolic and residue depletion studies, and efficacy trials of ABZ in aquatic animals to identify its application potential as a drug for aquatic animals. ABZ was depleted within 24h in the muscle tissues of hybrid striped bass, rainbow trout, and tilapia. In muscle tissue with adhering skin obtained from tilapia and largemouth bass, a significant quantity of the amino-sulfone metabolite of ABZ (ABZ-SO2NH2) was present, while no ABZ-SO2NH2 was detected in hybrid striped bass, channel catfish, and patinga. Fish exposed only to high doses of ABZ showed reduced red blood cell counts and hemoglobin levels and increased lymphocytes. Such signs of toxicity have also been observed in human patients and animal studies. At a dose of 100mg/L, ABZ showed 100% efficacy in eels. In addition, albendazole sulfoxide (ABZSO) demonstrated efficacies of 96.1% and 100% in pirapatinga and ray-finned fish, respectively, at a dose 500mg/L. ABZ was also highly effective in treating an intracellular parasite E. hepatopenaei in white shrimp. The application of ABZ in aquatic animals under the low-dose and short-term conditions is considered a reasonable solution to manage parasite infections. The types and residual periods of degradation products differed among fish species, suggesting dissimilar metabolic pathways. With a high demand for new alternative veterinary drugs in aquaculture by fish farmers, this review offers important evidence for considering the use of ABZ in Korean farmed fish, taking food safety issues into account.