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This study investigates the correlation between body mass index (BMI) and osteoporosis utilizing data from the Taiwan Biobank. Initially, a comprehensive analysis of 119,009 participants enrolled from 2008 to 2019 was conducted to assess the association between BMI and osteoporosis prevalence. Subsequently, a longitudinal cohort of 24,507 participants, initially free from osteoporosis, underwent regular follow-ups every 2–4 years to analyze the risk of osteoporosis development, which was a subset of the main cohort. Participants were categorized into four BMI groups: underweight (BMI < 18.5 kg/m 2 ), normal weight (18.5 kg/m 2  ≤ BMI < 24 kg/m 2 ), overweight (24 kg/m 2  ≤ BMI < 27 kg/m 2 ), and obese groups (BMI ≥ 27 kg/m 2 ). A T-score ≤ − 2.5 standard deviations below that of a young adult was defined as osteoporosis. Overall, 556 (14.1%), 5332 (9.1%), 2600 (8.1%) and 1620 (6.7%) of the participants in the underweight, normal weight, overweight and obese groups, respectively, had osteoporosis. A higher prevalence of osteoporosis was noted in the underweight group compared with the normal weight group (odds ratio [OR], 2.20; 95% confidence interval [95% CI], 1.99 to 2.43; p value < 0.001) in multivariable binary logistic regression analysis. Furthermore, in the longitudinal cohort during a mean follow-up of 47 months, incident osteoporosis was found in 61 (9%), 881 (7.2%), 401 (5.8%) and 213 (4.6%) participants in the underweight, normal weight, overweight and obese groups, respectively. Multivariable Cox proportional hazards analysis revealed that the risk of incident osteoporosis was higher in the underweight group than in the normal weight group (hazard ratio [HR], 1.63; 95% CI 1.26 to 2.12; p value < 0.001). Our results suggest that BMI is associated with both the prevalence and the incidence of osteoporosis. In addition, underweight is an independent risk factor for developing osteoporosis. These findings highlight the importance of maintaining normal weight for optimal bone health.

Obesity increases the risk of several diseases, including kidney stone disease (KSD). The study aimed to explore the relationship between KSD and various obesity-related indices. A total of 121,605 participants in the Taiwan Biobank from December 2008 to February 2020 were analyzed. The association between self-reported history of KSD and eight obesity-related indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), abdominal volume index (AVI), body roundness index (BRI), conicity index, and triglyceride glucose index was examined in cross-sectional analysis; additionally, the risk of developing kidney stones was analyzed in a longitudinal cohort of 25,268 participants without KSD at baseline, which was a subset of the main cohort. Of all participants, 77,904 (64.1%) were female. Overall, 10.7% of males and 4.0% of females had KSD. Multivariate-adjusted logistic regression showed that all obesity-related indices were significantly associated with KSD. During a mean follow-up of 47 months, kidney stones occurred in 642 (2.5%) participants, and after adjusting for confounders, the risk of developing kidney stones was higher in participants with higher BMI, WC, WHtR, WHR, AVI and BRI. BMI, WC, WHtR, WHR, AVI, and BRI were found to be associated with a higher prevalence of kidney stones as well as development of incident kidney stones, which could be used as predictive factors for development of KSD in clinical practice.

Recurrent and hormone-refractory prostate cancer (PCA) exhibits aggressive behaviors while current therapeutic approaches show little effect of prolonging the survival of patients with PCA. Thus, a deeper understanding of the patho-molecular mechanisms underlying the disease progression in PCA is crucial to identify novel diagnostic and/or therapeutic targets to improve the outcome of patients. Recent evidence suggests that activation of Wnt signaling in cancer stem cells (CSCs) contributes to cancer progression in malignant tumors. Here, we report that a novel Wnt co-activator ASPM (abnormal spindle-like microcephaly associated) maintains the prostate CSC subpopulation by augmenting the Wnt-β-catenin signaling in PCA. ASPM expression is incrementally upregulated in primary and metastatic PCA, implicating its potential role in PCA progression. Consistently, downregulation of ASPM expression pronouncedly attenuated the proliferation, colony formation, and the invasive behavior of PCA cells, and dramatically reduced the number of ALDH + CSCs and inhibited cancer stemness and tumorigenicity. Mechanistically, ASPM interacts with disheveled-3 (Dvl-3), a cardinal upstream regulator of canonical Wnt signaling, and inhibits its proteasome-dependent degradation, thereby increasing its protein stability and enabling the Wnt-induced β-catenin transcriptional activity in PCA cells. In keeping with the role of ASPM as a CSC-regulator, ASPM co-localizes with ALDH in PCA tissues and its expression exhibits high intra-tumoral heterogeneity. The proportion of high-ASPM-expressing cells in the tumor inversely correlates with the relapse-free survival of PCA patients. Collectively, our data points to ASPM as a novel oncoprotein and an essential regulator of Wnt signaling and cancer stemness in PCA, which has important clinical and therapeutic significance.

Smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD), however evidence from large-scale studies on whether secondhand smoke (SHS) increases the risk of COPD is still lacking. We conducted this large longitudinal study to investigate the association between SHS and the development of COPD. This is a longitudinal study. Data on 6519 subjects who were never-smokers, had no history of COPD, and had complete lung function records were extracted from the Taiwan Biobank. They were divided into two groups according to SHS exposure: no exposure and exposure groups. Data were collected when participants enrolled in the study and during regular follow-up. Cox proportional hazards regression models were used to estimate the relative risk (RR) and 95% confidence interval (CI) for the association between SHS and the risk of developing COPD. At 48 months of follow-up, 260 (4%) participants in the no exposure group and 34 (7%) participants in the exposure group developed COPD. The RR of incident COPD development was significantly higher in the exposure group than that in the no exposure group after adjusting for confounders (RR = 1.49; 95% CI 1.04 to 2.14; P value = 0.031). There is a dose–response relationship between the duration of exposure to SHS and the risk of incident COPD, which demonstrates that an additional hour of exposure to SHS per week was associated with a 1.03-fold increased likelihood of developing COPD after adjusting for confounders (RR = 1.03; 95% CI 1.00 to 1.05; P value = 0.027). SHS exposure contributes to the development of COPD. This finding can help raise awareness of the harms of SHS and provide a reference for formulating anti-smoking policies.

The purpose of this study was to investigate genetic factors associated with metabolic syndrome (MetS) by conducting a large-scale genome-wide association study (GWAS) in Taiwan, addressing the limited data on Asian populations compared to Western populations. Using data from the Taiwan Biobank, comprehensive clinical and genetic information from 107,230 Taiwanese individuals was analyzed. Genotyping data from the TWB1.0 and TWB2.0 chips, including over 650,000 single nucleotide polymorphisms (SNPs), were utilized. Genotype imputation using the 1000 Genomes Project was performed, resulting in more than 9 million SNPs. MetS was defined based on a modified version of the Adult Treatment Panel III criteria. Among all participants (mean age: 50 years), 23% met the MetS definition. GWAS analysis identified 549 SNPs significantly associated with MetS, collectively mapping to 10 genomic risk loci. Notable risk loci included rs1004558, rs3812316, rs326, rs4486200, rs2954038, rs10830963, rs662799, rs62033400, rs183130, and rs34342646. Gene-set analysis revealed 22 associated genes: CETP, LPL, APOA5, SIK3, ZPR1, APOC1, BUD13, MLXIPL, TOMM40, GCK, YKT6, RPS6KB1, FTO, VMP1, TUBD1, BCL7B, C19orf80 (ANGPTL8), SIDT2, SENP7, PAFAH1B2, DOCK6, and FOXA2. This study identified genomic risk loci for MetS in a large Taiwanese population through a comprehensive GWAS approach. These associations provide novel insights into the genetic basis of MetS and hold promise for the potential discovery of clinical biomarkers.

In response to a variety of stresses, mammalian cells activate the inflammasome for targeted caspase-dependent pyroptosis. The research community has recently begun to deduce that the activation of inflammasome is instigated by several known oncogenic stresses and metabolic perturbations; nevertheless, the role of inflammasomes in the context of cancer biology is less understood. In manipulating the expression of inflammasome, researchers have found that NLRP3 serves as a deterministic player in conducting tumor fate decisions. Understanding the mechanistic underpinning of pro-tumorigenic and anti-tumorigenic pathways might elucidate novel therapeutic onco-targets, thereby providing new opportunities to manipulate inflammasome in augmenting the anti-tumorigenic activity to prevent tumor expansion and achieve metastatic control. Accordingly, this review aims to decode the complexity of NLRP3, whereby summarizing and clustering findings into cancer hallmarks and tissue contexts may expedite consensus and underscore the potential of the inflammasome in drug translation.

It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan. Association of PSA with demographic, lifestyle, clinical characteristics (for cases), and the aldo–keto reductase 1C3 ( AKR1C3 ) rs12529 genetic polymorphisms were analysed using multiple linear regression and univariate modelling. Pooled multivariable analysis of cases showed that PSA was significantly associated with demographic, lifestyle, and clinical data with an interaction between ethnicity and age further modifying the association. Pooled multivariable analysis of controls data also showed that demographic and lifestyle are significantly associated with PSA level. Independent case and control analyses indicated that factors associated with PSA were specific for each cohort. Univariate analyses showed a significant age and PSA correlation among all cases and controls except for the US-European cases while genetic stratification in cases showed variability of correlation. Data suggests that unique PSA cut-off thresholds factorized with demographics, lifestyle and genetics may be more appropriate for prostate cancer screening.

Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial–mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.

This study investigated the associations of particulate matter (PM 2.5 /PM 10 ) and wet-bulb globe temperature (WBGT) with incident depression. Participants were recruited from the Taiwan Biobank. Exposure to air pollutants and WBGT was calculated using geospatial artificial intelligence (Geo-AI) estimation. Depression was assessed via self-reported questionnaires, and multivariable-adjusted Cox regression models were used for analysis. A total of 21,445 participants were enrolled, among whom 263 (1.2%) developed depression over an average follow-up period of 43 months. Participants in the highest quartile of PM 2.5 exposure had a significantly increased depression risk (HR 1.844, 95% CI 1.315–2.587). PM₁₀ exposure was also positively associated with depression, though the association was less consistent across analyses. The greatest risk was observed among individuals residing in areas with both elevated PM and WBGT levels. Higher exposure to PM 2.5 was consistently associated with increased depression risk. These findings highlight the potential combined effects of air pollution and heat stress on mental health in subtropical regions.

Docetaxel‐based chemotherapy has generally been considered as one of the effective treatments for castration‐resistant prostate cancer (PCa). However, clinical treatment with docetaxel often encounters a number of undesirable effects, including drug resistance. Tubulin isoforms have been previously examined for their resistance to docetaxel in many cancers, but their real mechanisms remained unclear. In this study, a series of docetaxel‐resistant PC/DX cell sublines were established by chronically exposing PC3 to progressively increased concentrations of docetaxel. Western blotting results showed significantly higher expression of acetyl‐tubulin, α‐tubulin, β‐tubulin, γ‐tubulin, and βIII‐tubulin in PC/DX25 than in parental PC3 cells. PC/DX25 with greater resistance to docetaxel had higher levels of acetyl‐tubulin and mitotic centromere‐associated kinesin (MCAK) than PC3 cells. This study found that docetaxel induced the expression of acetyl‐tubulin and MCAK in PC3 cells at a dose‐ and time‐dependent manner. Both mRNA and protein levels of histone deacetylase 6 (HDAC6) were significantly decreased in PC/DX25 compared with PC3 cells. PC3 increased the resistance to docetaxel by HDAC6 knockdown and Tubastatin A (HDAC6 inhibitor). Conversely, PC/DX25 reversed the sensitivity to docetaxel by MCAK knockdown. Notably, flow cytometry analysis revealed that MCAK knockdown induced significantly sub G1 fraction in PC/DX cells. Overexpression of polo‐like kinase‐1 increased the cell survival rate and resistance to docetaxel in PC3 cells. Moreover, epidermal growth factor receptor (EGFR) activation induced the upregulation of acetyl‐tubulin in docetaxel‐resistant PCa cells. These findings demonstrated that the EGFR‐mediated upregulated expression of acetyl‐tubulin played an important role in docetaxel‐resistant PCa.