Daniel Tzu-Hsuan Chen

The role of the gut microbiota in carcinogenesis is increasingly being acknowledged. Recent studies in multiple breast cancer mouse models have found that antibiotics, by altering the gut microbiota, can accelerate tumour growth. In humans, a recent cohort study restricted to triple negative breast cancer showed that breast cancer patients using a greater number of antibiotics had markedly worse survival. These studies have raised concerns about repeated antibiotic use in breast cancer patients. In this Registered Report, we investigated whether breast cancer patients using oral antibiotics had increased breast cancer-specific mortality. In population-based cohorts (n = 44,452), we did not observe a statistically significant association between antibiotic prescriptions after diagnosis and breast cancer-specific mortality (adjusted HR = 1.07 95% CI 0.87, 1.33) apart from prescriptions of 12 or more antibiotics (adjusted HR = 1.62 95% CI 1.31, 2.01). This association was weaker after adjustment for infections (adjusted HR = 1.44 95% 1.14, 1.81), when restricted to antibiotics within five years (adjusted HR = 1.33 95% 0.95, 1.84), and was similar for deaths from other causes (adjusted HR = 1.69 95% 1.19, 2.41). Frequent antibiotic users had higher cancer-specific mortality but the attenuation of associations in sensitivity analyses, and similar findings for other causes of death, suggest this increase may reflect residual confounding. Protocol registration: The Stage 1 protocol for this Registered Report was accepted in principle on 7 November 2023. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.24746721.v1 .

Renal cell carcinoma (RCC) presents significant therapeutic challenges due to its resistance to conventional treatments. Natural compounds with photodynamic properties, such as chlorophyll derivatives, offer potential for novel interventions. This study investigates the apoptotic effects of a chlorophyll-enriched green propolis compound activated by daylight-mediated photodynamic therapy (PDT) on RCC cells. A novel compound formulated from standardized ethanol extracts of Taiwanese green propolis, wheatgrass, and mulberry leaves was characterized using high-performance liquid chromatography (HPLC). Human RCC 786-O cells were treated with varying concentrations of the compound, with or without daylight PDT (570 nm). Cell viability was assessed via MTT assay, and median effective concentrations (EC₅₀) were calculated. HPLC analysis identified Artepillin C as the major constituent. The compound induced dose-dependent cytotoxicity, which was significantly enhanced by daylight PDT. EC₅₀ values dropped from 3.027 µL (compound alone) to 1.728 µL (with PDT), indicating synergistic efficacy. Cell viability significantly decreased in PDT-treated cells compared to non-treated controls (p < 0.05) indicating apoptosis. Daylight-activated PDT significantly amplifies the anticancer efficacy of the compound against RCC cells. Preliminary data suggest the potential of chlorophyll-enriched green propolis photodynamic activation (GPDT) as a natural adjunctive strategy for RCC, warranting further in vivo investigation.

Glioblastoma, an aggressive brain cancer, has limited treatment options and poor prognosis. Taiwanese green propolis, known for its tumor-inhibitory properties, shows promise when combined with photodynamic therapy (PDT), a targeted, low-toxicity treatment. This study investigated a novel Taiwanese green propolis-based compound for inducing apoptosis in glioblastoma cells and its synergistic potential with daylight PDT. Ethanol extracts of green propolis, wheatgrass, and mulberry leaves were combined and analyzed using High-Performance Liquid Chromatography (HPLC). Apoptosis induction in U87 glioblastoma cells was assessed via the MTT assay following treatment with the compound alone and in combination with daylight PDT at 570 nm. We identified Artepillin C as the main active component in the compound by HPLC, which significantly induced apoptosis in glioblastoma cells. Combined with daylight PDT, it demonstrated enhanced efficacy, with cell viability reduced from 95.2% at 0.25 µL to 11.3% at 8 µL of the compound extract. The EC₅₀ decreased, indicating greater apoptotic activity compared to the extract alone. This study provides the first in vitro evidence of synergistic anti-tumor effects of a Taiwanese green propolis-based compound daylight PDT (GPDT), highlighting a promising novel therapeutic approach that warrants further clinical investigation.

Introduction: Disposable e-cigarettes are the predominant type of vaping product used by adolescents and pose a significant public health concern. Identifying factors contributing to this growing trend is essential to curbing the vaping epidemic among youths. This study aims to investigate the...

Background: Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination. Methods: We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case–control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest. Results: Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77–0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) in the immunocompromised population, versus 85% (95%CI 83–86) and 86% (95%CI 85–89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions. Conclusions: COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes.

Immunocompromised individuals face increased risks of severe COVID-19 outcomes, underscoring the importance of receiving COVID-19 vaccination. However, there's a lack of comprehensive real-world data on their COVID-19 vaccine uptake, effectiveness, and safety profile. We analysed data in the QResearch UK database from 01/12/2020 to 11/04/2022. We included 12,274,948 people aged ≥ 12 years in our analysis, of whom 583,541 (4.8%) were immunocompromised, defined as on immune-modifying drugs, chemotherapy, organ transplants, or dialysis. Overall, 93.7% of immunocompromised patients received at least one COVID-19 vaccine dose. Uptake reduced with increasing deprivation (Hazard Ratio [HR] 0.78 [95% CI 0.77–0.79] in the most deprived quintile compared to the least for the first dose). Using a nested case-control design, estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to the unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) for the immunocompromised, versus 85% (95%CI 83–86) and 86% (95%CI 85–89) respectively for the general population. COVID-19 vaccines were protective against intensive care unit admission and death in both groups. There were no differing risks of adverse events during the first 28 days after each dose between the two populations. These findings underscore the importance of ongoing vaccination prioritisation for immunocompromised individuals to maximise protection against severe COVID-19-related outcomes.