Ya-Li Huang’s research while affiliated with Taipei Medical University and other places

In renal cell carcinoma (RCC), tissue inhibitor of metalloproteinase (TIMP) 3 expression is lost, suggesting that the TIMP3 gene may function as a tumor suppressor gene. Cadmium (Cd) and arsenic (As) exposure may affect the expression of TIMP3. Here we investigate the association of clear cell RCC with TIMP3 polymorphisms, and explore whether TIMP3 polymorphisms modify the relationship between blood Cd or total urinary As levels and clear cell RCC respectively. We recruited 281 clear cell RCC patients and 689 sex- and age-matched controls. The clear cell RCC was diagnosed by pathological evaluation after image-guided biopsy or surgical resection of the renal tumor. Concentrations of blood Cd and lead, and also total urinary As, were measured. We determined TIMP3 polymorphisms using the Agena Bioscience MassARRAY system. Odds ratio (OR) of clear cell RCC was significantly inversely correlated with TIMP3 rs9609643 GA/AA genotype, with OR = 0.63 (95% confidence interval, CI, 0.44–0.91). For TIMP3 rs715572 AA compared to the GG/GA genotype, the OR of clear cell RCC was 1.60 with 95% CI of 1.01–2.56. Individuals with high blood Cd concentrations and the TIMP3 rs9609643 GG genotype exhibited a higher OR of clear cell RCC than reference groups (OR = 4.48, 95% CI 2.09–9.60). This study presents a novel finding that the GA/AA genotype of TIMP3 rs9609643 significantly decreased the clear cell RCC risk, and AA genotype of TIMP3 rs715572 significantly increased the clear cell RCC risk. Furthermore, this study first identified that the TIMP3 rs9609643 risk genotypes appear to interact with high blood Cd levels to increase the OR of clear cell RCC. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-025-94807-3.

Background: Machine learning algorithms (MLA) gained prominence in nutritional epidemiology for analyzing dietary associations and uncovering intricate patterns within data. We explored dietary patterns associated with serum iron biomarkers and vitamin D among pregnant women, utilizing MLA to perform predictive analyses.Methods: The cross-sectional study utilized a secondary dataset from the Nationwide Nutrition and Health Survey in Taiwan, and 1,423 expectant mothers were recruited. Dietary patterns were predicted using K-means cluster analysis on semi quantitative food frequency data. Associations between serum biomarkers and dietary patterns were analyzed using binomial logistic regression, adjusting for sociodemographic and dietary variables. MLA including support vector machine, K-nearest neighbor, naive Bayes, random forest, and decision tree were applied to predict the accuracy of the dietary patterns in improving anemia-related biomarkers.Results: The K-means clustering identified two dietary patterns: LP + LA (low plant, low animal) and MP + LA(moderate plant, low animal). Logistic regression revealed that expectant mothers following the MP + LA pattern had a lower likelihood of low serum iron (OR = 0.45, 95 % CI 0.34–0.60) and ferritin (OR = 0.27, 95 % CI 0.21–0.36), but a higher likelihood of low 25(OH) vitamin D. MLA models demonstrated 70 %–76 % accuracy in identifying dietary pattern associated with improvement in serum iron and ferritin levels.Conclusions: The MP + LA dietary pattern exhibits a positive association with serum iron biomarkers and a negative association with 25(OH) vitamin D. Machine learning models demonstrate comparable predictive ac-curacy, highlighting their utility in nutritional epidemiology for identifying dietary patterns and their relationships with biochemical markers.

Pre-pregnancy overweightness or obesity affects nutritional status and micronutrient imbalance such as folate and iron during pregnancy. We studied the relationships between micronutrient intake and dietary patterns with serum folate and iron biomarkers among pregnant population with pre-pregnancy overweightness or obesity. This cross-sectional study utilized data from 2017-2019 Nationwide Nutrition and Health Survey. Participants (n = 436) were Taiwanese pregnant women with pre-pregnancy overweightness or obesity. Dietary evaluation was conducted by food frequency questionnaire and 24-hour dietary recall. Dietary patterns were developed by principal component analysis. Serum folate and iron biomarkers were measured. Logistic and linear regression models were employed to investigate the associations of dietary patterns with serum folate and iron biomarkers. Participants with the highest tertile of serum folate were older, and had less proportion of high parity. After adjusting covariates, the intake of DP-1 (mushrooms, roots, and dairy DP) (β = 0.052; 95% CI = 0.008-0.119; p < 0.05) or DP-3 (vegetables and fruits DP) (β = 0.056; 95% CI = 0.034-0.076; p < 0.05) was associated with increased serum folate. The consumption of DP-4 (animal DP) showed a significant association with elevated serum iron, ferritin, and vitamin B-12. The consumption of DP-1 or DP-3 was linked to a decreased risk of low serum folate. However, the intake of DP-3 was correlated with an increased risk of low serum ferritin. A reduced risk of low serum iron and vitamin B-12 was observed in participants consuming DP-4. The dairy and plant dietary patterns were positively associated with serum folate, and the animal dietary pattern was positively correlated with serum iron and vitamin B-12 in pregnant women with pre-pregnancy overweightness or obesity.

DNA methylation is a critical step in brain development, 5-Methyl-2'-deoxycytidine (5mdC) is one of the global DNA methylation markers. Arsenic and lead exposures have been associated with neurotoxicity, which may be linked to epigenetic changes. Our research sought to investigate the correlation between 5mdC and developmental delay (DD) among preschoolers. Additionally, we assessed whether 5mdC modified the impacts of blood lead and total urinary arsenic levels on DD. We analyzed the concentrations of 5mdC, blood cadmium and lead, and total urinary arsenic in 174 children with DD and 88 healthy children. Global DNA methylation levels are expressed as the ratio 5mdC/2’-dexyguanosine (dG), called 5mdC (%). In our findings, elevated levels of blood lead and total urinary arsenic were significantly associated with DD risk among preschoolers. Furthermore, high 5mdC (%) was related with reduced risk of DD, with an odds ratio (OR) and 95% confidence interval (CI) of 0.14 (0.06 – 0.32). A notable multiplicative interaction was observed between low 5mdC (%) and elevated blood lead levels to increase OR of DD, with OR and 95% CI was 9.51 (4.18 – 21.64). The findings provide evidence of the combined effects of reduced 5mdC (%) and high blood lead concentrations, increasing the OR of DD.

Purpose Vitamin D supplementation positively impacts anemia, but the relationship between a ferritin-related dietary pattern, iron parameters, and vitamin D in anemia is unclear. Methods This cross-sectional study analyzed data from the 2017–2019 National Nutrition and Health Survey, including 1423 pregnant women over 15 years old. Dietary intake was assessed using a semi-quantitative food frequency questionnaire and a 24-hour dietary recall. The FrDP was identified using reduced rank regression with blood parameters as response variables and 32 food groups as predictors. Linear and binomial logistic regression analyses evaluated the associations between the FrDP and serum biomarkers, adjusting for demographic and dietary variables. Risk associations between the FrDP and vitamin D concentrations were also assessed. Results The FrDP explained 18.5% of the variation in 6 response variables and was characterized by high consumption of fish, soy, gluten pasta, nuts, organ meat, pickled vegetables, and marine plants. The FrDP correlated positively with serum hemoglobin (r = 0.76), iron (r = 0.52), ferritin (r = 0.79), folate (r = 0.86), and vitamin B12 (r = 0.86). Linear regression revealed a positive association between the FrDP and serum iron. Women in the highest FrDP tertile were less likely to have low serum iron (OR = 0.65, 95% CI 0.50–0.85) but more likely to have low 25(OH) vitamin D concentrations (OR = 1.79, 95% CI 1.32–2.43). Conclusions The FrDP was positively associated with serum iron but negatively associated with serum 25(OH) vitamin D in pregnant women. Graphical Abstract

Melanoma is an aggressive tumor that is challenging to treat. Talimogene laherparepvec (T-VEC), the first oncolytic virus treatment approved by the US Food and Drug Administration to treat unresectable melanoma, was recently used in recurrent tumors after initial surgery. Our network meta-analysis aimed to compare T-VEC treatment of metastatic melanoma with treatment of granulocyte-macrophage colony-stimulating factor (GM-CSF) and control group. The protocol for this network meta-analysis was retrospectively registered with PROSPERO (CRD42022363321). Three databases, namely Embase, PubMed, and Cochrane Library, were searched until 10 June 2024. The search terms used were a combination of ‘metastatic melanoma’, ‘melanoma’, ‘T-VEC’, ‘talimogene laherparepvec’, and ‘GM-CSF’. Seven studies, with 978 participants receiving T-VEC treatment, 649 participants receiving GM-CSF treatment, and 938 participants constituting the control group, were included in our meta-analysis. For 1-year overall survival (OS), the league table revealed significant differences between the control and T-VEC groups [0.90 (0.83, 0.99)]. The disease-free survival (DFS) over 2 years was also analyzed showing no difference between the groups in DFS in the league table. T-VEC may be a favorable treatment for metastatic melanoma owing to the notable increase in OS. Nevertheless, due to the side effects and limitations, the clinical benefits of T-VEC therapy in metastatic melanoma should be interpreted cautiously. This network meta-analysis demonstrates that T-VEC may be a favorable choice of treatment for metastatic melanoma.

Photodynamic therapy (PDT) brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing; however, the low bioavailability of traditional photosensitizers (PSs) and their dependence on oxygen severely limits their application. Aggregation-induced emission (AIE) PSs can dramatically facilitate the photosensitization effect, which can have positive impacts on tumor PDT. To-date, most AIE PSs lack tumor targeting capability and possess poor cell delivery, resulting in their use in large quantities that are harmful to healthy tissues. In this study, a series of AIE PSs based on pyridinium-substituted triphenylamine salts ( TTPAs 1–6) with different alkyl chain lengths are synthesized. Results reveal that TTPAs 1–6 promote the generation of type I and II ROS, including ·OH and ¹O2. In particular, the membrane permeability and targeting of TTPAs 4-6 bearing C8-C10 side-chains are higher than TTPAs 1-3 bearing shorter alkyl chains. Additionally, they can assemble with albumin, thereby forming nanoparticles (TTPA 4–6 NPs) in situ in blood, which significantly facilitates mitochondrial-targeting and strong ROS generation ability. Moreover, the TTPA 4–6 NPs are pH-responsive, allowing for increased accumulation or endocytosis of the tumor and enhancing the imaging or therapeutic effect. Therefore, the in vivo distributions of TTPA 4–6 NPs are visually enriched in tumor sites and exhibited excellent PDT efficacy. This work demonstrates a novel strategy for AIE PDT and has the potential to play an essential role in clinical applications using nano-delivery systems.