MAIN METHODS: Neuroblastoma cell line SH-SY5Y was treated with β-amyloid (Aβ) to induce AD-like pathological changes, which serves as Alzheimer's disease model. Tβ4 was overexpressed in SH-SY5Y cells by lentivirus infection, and downregulated by siRNA transfection. Apoptosis of transfected SH-SY5Y cells after Aβ-treatment was examined by western blot and flow cytometry. Apoptotic proteins and Tβ4-related signaling pathways were also investigated by western blot.
KEY FINDINGS: We found that Tβ4 overexpression increased viability and suppressed apoptosis of Aβ-treated SH-SY5Y cells. Tβ4 ameliorated oxidative damage and suppressed reactive oxygen species production in Aβ-treated SH-SY5Y cells. Consistently, Tβ4 overexpression down-regulated the expression levels of pro-apoptotic markers such as Caspase-3, Caspase-8, and Bax, while up-regulated the expression level of anti-apoptotic gene Bcl-2 in Aβ-stimulated SH-SY5Y cells. Mechanistically, we demonstrated that Tβ4 dampened ERK/p38 MAPK signaling and enhanced 5-HTR1A expression in Aβ-treated SH-SY5Y cells. Moreover, we revealed that Tβ4 inhibited the activation of ERK pathway through up-regulating 5-HTR1A in Aβ-treated SH-SY5Y cells.
SIGNIFICANCE: Taken together, our findings provide evidences to support the neuroprotective role of Tβ4 and might open up new therapeutic applications of Tβ4 in AD treatment.
METHODS: A life table model was constructed using published Malaysian demographic and mortality data. Our analysis was limited to male smokers due to the low smoking prevalence in females (1.1%). Male smokers aged 15-64 years were followed up until 65 years or until death. The population attributable risk, health-related quality of life decrements and relative reduction in productivity due to smoking were sourced from published data. The analysis was repeated assuming the cohorts were never smokers, and the differences in outcomes represented the health and productivity burden conferred by smoking. The cost of productivity loss was estimated based on the gross domestic product per equivalent full-time worker in Malaysia.
RESULTS: Tobacco use is highly prevalent among working-age males in Malaysia, with 4.2 million (37.5%) daily smokers among men aged between 15 and 64 years. Overall, our model estimated that smoking resulted in the loss of over 2.1 million life years (2.9%), 5.5 million (8.2%) quality-adjusted life years (QALYs) and 3.0 million (4.8%) PALYs. Smoking was estimated to incur RM275.3 billion (US$69.4 billion) in loss of productivity.
CONCLUSION: Tobacco use imposes a significant public health and economic burden among working-age males in Malaysia. This study highlights the need of effective public health interventions to reduce tobacco use.