Association of serum folate concentrations with the mortality of cancer: a prospective cohort study.

BACKGROUND: The association between serum folate concentrations and the mortality of cancer remains unclear. We aim to investigate the association of serum folate concentrations with all-cause and cause-specific mortality among American adults with cancer. METHODS: This cohort study included 4535 patients with cancer from National Health and Nutrition Examination Survey (NHANES) 1999 to 2016 and NHANES III (1988-1994). Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Cox proportional hazards model and two-piecewise Cox proportional hazards model were used to calculate hazard ratios and 95% confidence intervals for the associations between folate concentrations and the risk of mortality. RESULTS: During a median follow-up of 37,792 person-years, there were 1998 all-cause deaths and 616 cancer deaths. Non-linear and L-shaped associations were observed between serum folate concentrations and the risk of all-cause and cancer mortality among patients with cancer. Notably, the mortality rates reached a plateau at 23.7 ng/mL for all-cause mortality and 23.57 ng/mL for cancer mortality. When folate levels fell below these thresholds, the risk of all-cause and cancer mortality decreased by approximately 2.1% (HR 0.979; 95% CI 0.969-0.989) and 3.6% (HR 0.964; 95% CI 0.948-0.981), respectively, with each unit increase in the folate concentration up to the thresholds. CONCLUSION: Our study reveals that low serum folate concentrations are linked to an elevated risk of cancer mortality among individuals with cancer within a certain range and supplementation of folate in cancer patients to achieve specific serum folate level threshold (23.7 ng/mL) might reduce the risk of cancer mortality.

Impact of the tissue factor pathway inhibitor gene on apoptosis in human vascular smooth muscle cells.

Tissue factor pathway inhibitor (TFPI) plays a vitally important role in the blood coagulation pathway. Recent studies indicated that TFPI induces apoptosis in vascular smooth-muscle cells (VSMCs) in animals. The present study investigated whether the TFPI gene could also induce apoptosis in human vascular smooth-muscle cells (hVSMCs). Such cells were isolated from human umbilical arteries and subsequently transfected with pIRES-TFPI plasmid (2 µg/mL). MTT assaying and cell counting were applied to measure cell viability and proliferation, RT-PCR was utilized to analyze TFPI gene expression in the cells. Apoptosis was analyzed by fluorescence activated cell sorting (FACS). Several key proteins involved in apoptosis were examined through Western blotting. It was shown that TFPI gene transfer led to its increased cellular expression, with a subsequent reduction in hVSMC proliferation. Further investigation demonstrated that TFPI gene expression resulted in lesser amounts of procaspase-3, procaspase-8 and procascase-9, and an increased release of mitochondrial cytochrome c (cyt-c) into cytoplasm, thereby implying the involvement of both extrinsic and intrinsic pathways in TFPI gene-induced apoptosis in hVSMCs.

Impact of the tissue factor pathway inhibitor gene on apoptosis in human vascular smooth muscle cells

Tissue factor pathway inhibitor (TFPI) plays a vitally important role in the blood coagulation pathway. Recent studies indicated that TFPI induces apoptosis in vascular smooth-muscle cells (VSMCs) in animals. The present study investigated whether the TFPI gene could also induce apoptosis in human vascular smooth-muscle cells (hVSMCs). Such cells were isolated from human umbilical arteries and subsequently transfected with pIRES-TFPI plasmid (2 μg/mL). MTT assaying and cell counting were applied to measure cell viability and proliferation, RT-PCR was utilized to analyze TFPI gene expression in the cells. Apoptosis was analyzed by fluorescence activated cell sorting (FACS). Several key proteins involved in apoptosis were examined through Western blotting. It was shown that TFPI gene transfer led to its increased cellular expression, with a subsequent reduction in hVSMC proliferation. Further investigation demonstrated that TFPI gene expression resulted in lesser amounts of procaspase-3, procaspase-8 and procascase-9, and an increased release of mitochondrial cytochrome c (cyt-c) into cytoplasm, thereby implying the involvement of both extrinsic and intrinsic pathways in TFPI gene-induced apoptosis in hVSMCs.