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Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton's jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton's jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes. It was found that WJ-MSCs expressed more genes, especially secreted factors, involved in angiogenesis and neurogenesis. Functional validation showed that WJ-MSCs induced better neural differentiation and neural cell migration via a paracrine mechanism. Moreover, WJ-MSCs afforded better neuroprotection efficacy because they preferentially enhanced neuronal growth and reduced cell apoptotic death of primary cortical cells in an oxygen-glucose deprivation (OGD) culture model that mimics the acute ischemic stroke situation in humans. In terms of angiogenesis, WJ-MSCs induced better microvasculature formation and cell migration on co-cultured endothelial cells. Our results suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair. This study provides a basis for the development of cell-based therapy and carrying out of follow-up mechanistic studies related to MSC biology.

Previous research has shown an association between socioeconomic status (SES) and mortality, particularly in chronic diseases. However, limited studies simultaneously examined the relationship between urbanization, SES, exposure to PM2.5, and cerebrovascular disease (CBD) mortality at a township level from 2011 to 2020 in Taiwan. Township-level SES data (percentages of low-income and education with college and above) and seven levels of urbanization from 2011 to 2020 were obtained from data sources in Taiwan's central government. Age-standardized CBD mortality rates in 358 townships were calculated using the Geographic Information System (GIS) provided by the Research Center for the Humanities and Social Sciences (RCHSS) at Academia Sinica. Exposure to PM2.5 concentration was estimated using a combination of land-use regression and Ordinary Kriging to enhance the robustness of PM2.5 concentration estimates at the township level. Panel regression and structural equation modeling (SEM) was employed to analyze the association between urbanization, SES, exposure to PM2.5, and township-based CBD mortality rates. There are significant differences in SES variables and exposure to PM2.5 among townships with seven levels of urbanization (P < 0.001). Even after controlling for other covariates (SES and PM2.5 concentration) through multivariate analysis, the associations between CBD mortality rates and urbanization areas persisted. SEM analysis revealed a negative correlation between age-standardized CBD mortality rate and education levels (β = -0.22), but a positive correlation with the proportion of low-income individuals (β = 0.41). There was no significant association between exposure to PM2.5 and CBD mortality. The panel regression analysis revealed that socioeconomic variables had different effects on CBD mortality rates across the three models (pooled ordinary least squares, fixed-effects, and random-effects) in both urban and rural areas. Notably, the level of urbanization was observed to modify the relationship between socioeconomic variables and CBD mortality rates. Our findings suggest that township-based CBD mortality is significantly associated with SES variables and levels of urbanization, despite a reduction in CBD mortality from 2011 to 2020. Therefore, targeted intervention programs should be implemented to reduce CBD mortality in different levels of urbanization, particularly in remote townships. It is necessary to assess the disparities in socioeconomic status to achieve a fair allocation of resources at the township level.

Cancer patients with diabetes have an increasing risk of Dox-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes. We aimed to investigate the potential of dapagliflozin for preventing doxorubicin (Dox)-induced cardiotoxicity. Using Taiwan National Health Insurance Database, the incidence of heart failure of cancer patients with or without diabetes was investigated. Streptozotocin (STZ)-induced diabetic rats were pretreated with oral dapagliflozin for 6 weeks followed by Dox for 4 weeks via intraperitoneal injection. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes cultured in high glucose were treated with dapagliflozin at 10 μM and subsequently exposed to Dox at 1 μM. Apoptosis and endoplasmic reticulum (ER) stress-related protein expression were measured. Among the studied patients, those with diabetes had a higher risk of major adverse cardiovascular events including the development of heart failure. In diabetic rats, dapagliflozin reduced cardiac fibrosis and significantly improved cardiac function. Dapagliflozin effectively inhibited Dox-induced apoptosis and reactive oxygen species in cardiomyocytes under high glucose. Mechanistically, we showed that dapagliflozin decreased the cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2. Dapagliflozin also significantly reduced ER stress-associated proteins including GRP78, PERK, eIF-2α, ATF-4, and CHOP. Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes. These results indicate that dapagliflozin could be useful for preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment.

Background/Objective Limited evidence exists regarding the socioeconomic inequalities in cerebrovascular disease (CBD) mortality at different urbanization levels. Therefore, this study was conducted to assess the socioeconomic inequalities and urbanization levels in township-based CBD mortality in Taiwan. Methods Socioeconomic variables, including the percentages of low-income households, individuals with a university education and above, and tax payments, were measured at the township level from 2011 to 2020. Urbanization was also determined by the national survey and divided into seven levels. Age-standardized mortality rate (ASMR) of CBD was calculated using a Geographic Information System (GIS) in 358 townships. The effects of socioeconomic variables and urbanization levels on relative and absolute inequalities in township-based CBD mortality rates were examined. Results Significant differences in ASMR of CBD were observed across all socioeconomic status indicators over the years. Higher proportions of low-income households were associated with higher ASMR of CBD. Conversely, there were negative correlations between higher proportions of individuals with a university education and above and tax payments with ASMR of CBD. The regression analysis indicated significant impacts of relative and absolute socioeconomic inequalities on ASMR of CBD. Additionally, a moderation effect of socioeconomic variables and urbanization on CBD mortality rates was observed, with rural areas showing sensitivity to these factors. Conclusion Although ASMR of CBD showed significant decreases over time, socioeconomic inequalities in CBD mortality rates persist. Interventions targeting socioeconomic inequalities in health outcomes, especially in rural areas, are needed to address this issue.

Background Early diagnosis of low ejection fraction (EF) remains challenging despite being a treatable condition. This study aimed to evaluate the effectiveness of an electrocardiogram (ECG)-based artificial intelligence (AI)-assisted clinical decision support tool in improving the early diagnosis of low EF among inpatient patients under non-cardiologist care. Methods We conducted a pragmatic randomized controlled trial at an academic medical center in Taiwan. 13,631 inpatient patients were randomized to either the intervention group ( n  = 6,840) receiving AI-generated ECG results or the control group ( n  = 6,791) following standard care. The primary outcome was the incidence of newly diagnosed low EF (≤ 50%) within 30 days following the ECG. Secondary outcomes included echocardiogram utilization rates, positive predictive value for low EF detection, and cardiology consultation rates. Statistical analysis included hazard ratios (HR) with 95% confidence intervals (CI) for time-to-event outcomes and chi-square tests for categorical variables. Results The intervention significantly increased the detection of newly diagnosed low EF in the overall cohort (1.5% vs. 1.1%, HR 1.50, 95% CI: 1.11–2.03, P  = 0.023), with a more pronounced effect among AI-identified high-risk patients (13.0% vs. 8.9%, HR 1.55, 95% CI: 1.08–2.21). While overall echocardiogram utilization remained similar between groups (17.1% vs. 17.3%, HR 1.00, 95% CI: 0.92–1.09), the intervention group demonstrated higher positive predictive value for identifying low EF among patients receiving echocardiogram (34.2% vs. 20.2%, p  < 0.001). Post-hoc analysis revealed increased cardiology consultation rates among high-risk patients in the intervention group (29.3% vs. 23.5%, p  = 0.027). Conclusions Implementation of an AI-ECG algorithm enhanced the early diagnosis of low EF in the inpatient setting, primarily by improving diagnostic efficiency rather than increasing overall healthcare utilization. The tool was particularly effective in identifying high-risk patients who benefited from increased specialist consultation and more targeted diagnostic testing. Trial registration ClinicalTrials.gov Identifier: NCT05117970.

The NLRP3 inflammasome is a multiprotein complex that plays a key role in the innate immune system, and aberrant activation of this complex is involved in the pathogenesis of inflammatory diseases. Carvedilol (CVL) is an α-, β-blocker used to treat high blood pressure and congestive heart failure; however, some benefits beyond decreased blood pressure were observed clinically, suggesting the potential anti-inflammatory activity of CVL. In this report, the inhibitory potential of CVL toward the NLRP3 inflammasome and the possible underlying molecular mechanisms were studied. Our results showed that CVL attenuated NLRP3 inflammasome activation and pyroptosis in mouse macrophages, without affecting activation of the AIM2, NLRC4 and non-canonical inflammasomes. Mechanistic analysis revealed that CVL prevented lysosomal and mitochondrial damage and reduced ASC oligomerization. Additionally, CVL caused autophagic induction through a Sirt1-dependent pathway, which inhibited the NLRP3 inflammasome. In the mouse model of NLRP3-associated peritonitis, oral administration of CVL reduced (1) peritoneal recruitment of neutrophils; (2) the levels of IL-1β, IL-18, active caspase-1, ASC, IL-6, TNF-α, MCP-1, and CXCL1 in the lavage fluids; and (3) the levels of NLRP3 and HO-1 in the peritoneal cells. Our results indicated that CVL is a novel autophagy inducer that inhibits the NLRP3 inflammasome and can be repositioned for ameliorating NLRP3-associated complications.

Needlestick and sharp injuries (NSIs) experienced by physicians have been identified as a major occupational hazard. Blood-borne pathogens resulting from the NSIs experienced by physicians pose severe physical and psychological threats to them, as well as people who are around them. However, there is little research focusing on physicians' behaviours to prevent NSIs. In the present study, we investigated the roles of safety climate, job demands experienced by physicians, and physicians' self-efficacy in affecting physicians' behaviours to prevent NSIs. 401 physicians from four teaching hospitals in Northern Taiwan were recruited to participate in an anonymous survey. Among them, 189 physicians returned the completed survey with a response rate of 47.1%. Overall, respondents reported frequently engaging in NSI prevention behaviours. As expected, safety climate in hospitals and physicians' self-efficacy to prevent NSIs were significantly related to their behaviours to prevent NSIs (r = 0.22 and r = 0.33, respectively). The moderating analysis also revealed that physicians with high self-efficacy tended to engage in NSI prevention behaviours regardless of levels of job demand they experienced. In contrast to our expectation, however, physicians with low self-efficacy engaged in more NSI prevention behaviours when job demands were high than when the demands were low. Our findings show the important roles safety climate, job demands and self-efficacy play in shaping physicians' NSI prevention behaviours. Hospitals may consider improving safety climate via strengthening management commitments to NSIs prevention, reducing job demands by training physicians to proactively redesign their own jobs, and increasing physicians' self-efficacy via well-designed skill-based training.

Police officers often face emotionally challenging interpersonal situations and numerous studies have demonstrated that policing is a stressful occupation. A study revealed a significant positive correlation between emotional demands among police officers and emotional dissonance, as well as burnout. Health-promoting behaviors can contribute to better overall health outcomes and reduce the risk of developing health problems, but there is limited research evaluating the association of job strain and health behaviors with mental health outcomes in police officers. The objective of this study was to assess the job strain associated with mental health mediated by health behaviors in Taiwanese police officers. This was a cross-sectional quantitative study conducted in Oct 2016. A total of 41,871 police officers (response rate was 79.7%) participated questionnaire that consisted of demographic information, job characteristics, health behaviors, and mental component summary (MCS) scores of the Short-Form Health Survey. Independent t-tests and one-way analysis of variance (One-way ANOVA) were conducted to assess the differences in mean MCS scores across various demographics, health behavior, and job characteristics. Multivariate regression analyses were used to assess the relationship between job strain and health behaviors with mental health outcomes. MCS scores were associated with job characteristics and health behaviors among police officers except for gender. After adjusting for covariates, multivariate analysis indicated that police officers with high job demands and high job strain index exhibited poor MCS scores. Job strain was significantly associated with MCS mediated by health behaviors (consumption of fruits and vegetables, and physical activity) in Taiwanese police officers. Since regular physical activity and increased vegetable and fruit consumption might alleviate the effects of job strain on mental health status, it is recommended that institutional policies be established to promote health-enhancing behaviors among police officers.

Background Although enterovirus 71 (EV71) is an important public health threat, especially in the Asia-Pacific region, there are still no effective drugs or vaccines to treat and prevent EV71 infection. Therefore, it is critical to develop prophylactic and therapeutic agents against EV71. Rosmarinic acid (RA), a phytochemical, has been discovered to possess a broad spectrum of biological activities. Methods The virucidal effects of RA on EV71 were determined by MTT, western blot, median cell culture infectious dose, apoptosis detection, plaque reduction, semi-quantitative real-time polymerase chain reaction, immunofluorescence detection, molecular docking analysis, and mouse protection assay. Results RA showed a strong protective effect against EV71 infection in human rhabdomyosarcoma cells when the multiplicity of infection was 1, with a low IC 50 value (4.33 ± 0.18 μM) and high therapeutic index (340). RA not only protected cells from EV71-induced cytopathic effects, but also from EV71-induced apoptosis. The results of time-of-addition analysis demonstrated that the inhibitory activity of RA was highest at the early stage of viral infection. Consistent with this, the infectivity of EV71 in the early stage of viral infection also was observed to be limited in neonatal mice treated with RA. Further, molecular docking predicts that RA could replace the natural pocket factor within the VP1 capsid-binding hydrophobic pocket. Conclusions This study suggests that RA has the potential to be developed as an antiviral agent against initial EV71 infection to prevent or reduce EV71-induced pathogenesis and complications, since RA can effectively reduce EV71 infection in the early stages of viral infection.

Background Since the policy of “keeping trash off of the ground” in Taiwan, long-term exposure to repetitive motion in waste collection process results in high risk of upper extremity musculoskeletal disorders (UEMDs). Thus, we assessed the moderation and mediation effects of job-related stress and job support on work-related UEMDs among municipal waste collectors. Methods A cross-sectional study was conducted in two cities located at northern Taiwan during 2018–2019. 626 municipal waste collectors voluntarily participated and anonymously filled out a structured questionnaire. The moderation and mediation effects of effort-reward imbalance (ERI) and social support on UEMDs were analyzed by Haye’s Process Macro Model. Results Prevalence of UEMDs in municipal waste collectors were 43.4% for neck, 56.0% for shoulder, 24.1% for upper back, and 33.1% for hand/wrist. There was high prevalence of shoulder (72.2%), neck (48%), and upper back (30%) in female workers compared to male, most significantly in shoulders. In univariate and multivariate analysis, high ERI and low job support were significantly associated with ORs of 3.11 (95% CI:1.58–6.13) for elbow, 2.79 (95% CI:1.39–5.56) for shoulder, 3.39 (95% CI:1.64–7.00) for upper back and 3.83 (95% CI:1.98–7.41) for hand/wrist. Prevalent UEMDs were positively associated with high ERI in municipal waste collectors but negatively with job support. The moderation effects of ERI and job support on UEMDs, of which the measured synergy index exceeded one, were 18.24 for shoulder, 3.32 for elbow, and 2.45 for hand/wrist, but mediation effects were not significant. Conclusions This study found municipal waste collectors with work-related upper extremity disorders were significantly associated with work-related psychological risk factors. Therefore, waste collection cannot only to be improved by semi-automatic and automatic processes but immediate intervention programs for the reduction of psychological risk factors is needed promptly.