National Health Research Institutes

While epidemiological studies link fine particulate matter (PM2.5) exposure to metabolic dysfunction-associated steatotic liver disease (MASLD) and renal dysfunction, a translational gap exists, as most animal models utilize acute, high-dose exposures that poorly reflect chronic, moderate-level human scenarios. To address this, we established a long-term (seven-month) mouse model (n = 8 per group) combining a Western diet (WD) with a chronic PM2.5 exposure paradigm equivalent to a human exposure of ~50 μg/m3, assessing key biomarkers, organ histopathology, and hepatic gene expression. While the WD was the primary driver of MASLD-related steatosis and insulin resistance, PM2.5 co-exposure acted as a distinct modifier of hepatic pathogenesis. Specifically, the WD + PM group exhibited significantly exacerbated hepatic pathology compared to WD alone, characterized by a ~55% increase in serum ALT (p < 0.05) and a 4.7-fold increase in collagen deposition area (p < 0.05), alongside the marked upregulation of pro-inflammatory (TNF-α, CCL2) and pro-fibrotic (α-SMA, COL1A1) genes. In the kidney, PM2.5 exposure independently elevated serum creatinine levels (by ~64% vs. controls, p < 0.05) and increased the incidence of proteinuria (75% in WD + PM vs. 0% in controls). These functional alterations occurred without inducing major structural damage. This study provides crucial experimental evidence that moderate, chronic air pollution aggravates diet-induced hepatic inflammation/fibrosis and contributes to early-stage renal dysfunction, underscoring the multi-organ health threats to metabolically vulnerable populations.

Precise regulation of Notch signalling is essential for proper eye development in Drosophila. Although the core components of Notch signalling are well characterised, the mechanisms modulating ligand activity remain less understood. Here, we identified microRNA miR-133 as a positive regulator of Notch signalling in a Drosophila eye model. In a Notch-sensitised background, miR-133 overexpression rescued the small-eye phenotype induced by fringe (fng), while miR-133 knockdown exacerbated this defect. miR-133 directly targets Synaptobrevin (Syb), a vesicle-associated SNARE protein, through a conserved site in its 3'UTR. Loss of Syb phenocopied miR-133 overexpression, whereas Syb overexpression enhanced Notch-related defects. miR-133 and Syb exhibited complementary expression patterns, and both miR-133 overexpression and Syb knockdown induced non-autonomous activation of Notch targets and accumulation of Delta and Serrate ligands at the plasma membrane. Furthermore, we show that the E3 ligase Godzilla (Gzl) and Rab11-dependent recycling are essential for Notch activation. Together, our findings revealed a miR-133/Syb/gzl/Rab11 regulatory axis that enhances Notch signalling by modulating ligand trafficking and distribution during development.

A BSTRACT Objectives: Vegan diet – the exclusion of all animal products, even eggs and dairy – ranked the most climate-friendly diet, but concerns persist regarding its nutritional adequacy, particularly for omega-3 fatty acids, vitamin D, and iodine. This study compares the nutritional status of fatty acids, vitamin D, and iodine, among Taiwanese vegans, vegetarians, and omnivores. Materials and Methods: This cross-sectional study included 45 omnivores, 46 lacto-ovo vegetarians, and 24 vegans. Blood and urine samples were collected to analyze nutritional biomarkers, including erythrocyte fatty acid profiles, plasma vitamin D, and urinary iodine. Results: Vegans had the lowest median percentage of saturated fatty acids, trans-fatty acids, and omega-3 fatty acids, including EPA and DHA, but the highest levels of omega-6 fatty acids. The medians (P25–P75) of omega-3 index values were 2.6 (2.4–2.8), 3.7 (3.2–4.5), and 5.8 (5.0–6.5) for vegans, vegetarians, and omnivores, respectively. Vitamin D deficiency was most prevalent among vegans (75%), followed by omnivores (36%) and vegetarians (24%). Iodine insufficiency was also more common in vegans (76%) than in vegetarians (57%) and omnivores (56%). Conclusion: Taiwanese vegan diets may be advantageous in lowering saturated fatty acids and trans-fatty acid status but may be associated with a higher risk of deficiency for omega-3 fatty acids, vitamin D, and iodine. Strategies to enhance the adequacy of these nutrients may be needed to improve the quality of vegan diets.

Abstract Intestinal ultrasound (IUS) is a non‐invasive imaging method used to evaluate bowel wall inflammation and monitor disease activity in inflammatory bowel disease (IBD) patients. Both the European Crohn's and Colitis Organization and the American Gastroenterological Association endorse IUS for monitoring disease activity and identifying complications at the point of care. However, to date, no published data are available regarding the use of IUS for IBD management in Taiwan. Similar to the specificity of IUS in visualizing gut inflammation, immunoglobulin A (IgA) is a key immunoglobulin central to gut mucosal immunity. Recent studies have explored the involvement of IgA in IBD, but the relationship between IgA levels and bowel wall inflammation was unknown. We enrolled 28 IBD patients, including 19 with ulcerative colitis (UC) and 9 with Crohn's disease (CD), from the outpatient clinic of China Medical University Medical Center. All patients underwent IUS between July 2023 and August 2024. Ultrasound scores were based on the Milan ultrasound criteria (MUC) for UC and the bowel ultrasound score (BUSS) for CD. Plasma levels of erythrocyte sedimentation rate, C‐reactive protein (CRP), albumin, IgA, partial Mayo score, and Crohn's disease activity index (CDAI) were collected at baseline, during treatment, and after 52 weeks of advanced therapy (Adalimumab, Vedolizumab, or Tofacitinib). IUS findings were closely correlated with disease activity. In UC, the MUC score was positively correlated with CRP ( R 2 = 0.4888, p &lt; .0001), partial Mayo score ( R 2 = 0.3652, p = .0002), and negatively with albumin levels ( R 2 = 0.3747, p = .0002). In CD, the BUSS score showed a positive correlation with CDAI ( R 2 = 0.2694, p = .0394). Plasma IgA levels were significantly associated with bowel wall thickness (BWT) in both UC and CD ( R 2 = 0.1759, p = .0041). Furthermore, plasma IgA was strongly correlated with the BUSS score ( R 2 = 0.6585, p = .0001) in CD patients. Notably, when BWT exceeded 3.5 mm, plasma IgA levels increased significantly ( p = .0025). These results demonstrate that IUS is an effective tool for monitoring disease activity and evaluating therapeutic responses in IBD patients. Besides, plasma IgA reflects the bowel wall inflammation, particularly in conjunction with IUS.

This study investigates the physiological and psychological restorative effects of transitions from urban environments to natural environments, with a focus on the presence or absence of water features. Addressing gaps in the understanding of the immediate health benefits of nearby nature, particularly urban blue spaces compared to green spaces, the study utilizes Virtual Reality (VR) technology to simulate these transitions. Sixty adult participants were randomly assigned to experience VR simulations of urban environments followed by either natural environments with water (blue spaces) or without water (green spaces). Physiological responses (heart rate, blood pressure, heart rate variability) and psychological responses (mood states, restorative components) were measured across three time points. The findings indicate a general trend of physiological relaxation over time, as evidenced by reduced heart rates, regardless of the type of natural environment viewed. Participants transitioning to environments with water also experienced greater reductions in negative emotions (fatigue, anger, depression) and higher increases in positive emotions (vigor) compared to those in environments without water. Although both green and blue spaces provided similar restorative effects, such as enhanced feelings of being away, fascination, and compatibility, water elements were more effective in boosting positive mood states. This study highlights the potential role of water features in enhancing relaxation and emotional well-being during urban-to-natural environment transitions. These findings suggest significant implications for urban design, advocating the inclusion of water elements to promote public health and foster more sustainable cities.

FK506-binding protein 51 (FKBP51, encoded by FKBP5) is a multisignaling cochaperone that regulates cellular stress responses and inflammatory signaling through the NF-κB pathway. Although FKBP51 is upregulated in reactive astrocytes, its role in epilepsy and excitotoxic neuroinflammation remains unknown. Excessive astrogliosis and impaired glutamate transporter-1 (GLT-1)-mediated glutamate clearance promote excitotoxicity and increase seizure susceptibility. Here, we investigated how both global and astrocyte-specific Fkbp5 deletions influence seizure susceptibility, astrogliosis, neuroinflammation, and cognition in male mice subjected to a kainic acid (KA)-induced epilepsy mouse model. Global Fkbp5 knockout (Fkbp5-KO) presented lower seizure activity along with decreased neuronal loss and astrogliosis in the hippocampus compared with the wild-type mice. Astrocyte-specific Fkbp5 conditional knockout (aFkbp5-cKO) mice similarly attenuated seizure severity, decreased astrogliosis, improved novel object recognition, and preserved GLT-1 expression in hippocampal CA3. Glia-neuron mixed cultures derived from Fkbp5-KO brains showed reduced NMDA-induced neurotoxicity and astrogliosis, accompanied by decreased NF-κB p65 phosphorylation. Notably, overexpression of an Fkbp5 quadruple mutant that disrupts the FKBP51-NF-κB interaction inhibited proinflammatory lipopolysaccharide-induced astrogliosis and NF-κB activation. Transcriptomic analysis of Fkbp5-KO hippocampi further confirmed suppression of NF-κB-driven inflammatory pathways. In summary, astrocytic FKBP51 mediates reactive astrogliosis and GLT-1 downregulation, linking excitotoxic neuroinflammation with seizure susceptibility and cognitive impairment, and represents a potential intervention target for epilepsy.