RESUMEN
While selenium is a cofactor of several antioxidant enzymes against cancer and is essential for human health, its excess intake may also be harmful. Though a safe intake of selenium has recently been recommended, it is not well understood in the Asian population. We aimed to determine the association between dietary intake of selenium and cancer risk in a case-control study of 3758 incident cancer cases (i.e., stomach, colon, rectum, lung cancers, and other sites) and 2929 control subjects in Vietnam. Daily intake of selenium was derived from a semiquantitative food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between selenium intake and cancer risk. We observed a U-shaped association between selenium intake and cancer risk. A safe intake ranged from 110.8 to 124.4 µg/day (mean 117.8 µg/day). Compared to individuals with the safe intake of selenium, individuals with the lowest intake (i.e., 27.8-77.2 µg/day) were associated with an increased risk of cancer (OR = 3.78, 95% CI 2.89-4.95) and those with the highest intake (169.1-331.7 µg/day) also had an increased cancer risk (OR = 1.86, 95% CI 1.45-2.39). A U-shaped pattern of association between selenium intake and cancer risk was stronger among participants with body mass index (BMI) < 23 kg/m2 and never smokers than BMI ≥ 23 kg/m2 and ever smokers (P'sheterogeneity = 0.003 and 0.021, respectively) but found in both never and ever-drinkers of alcohol (Pheterogeneity = 0.001). A U-shaped association between selenium intake and cancer risk was seen in cancer sites of the stomach, colon, rectum, and lung cancers. In summary, we found a U-shaped association between selenium intake and cancer risk and a safe selenium intake (mean: 117.8 µg/day) in the Vietnamese population. Further mechanistic investigation is warranted to understand better a U-shaped association between selenium intake and cancer risk.
Asunto(s)
Neoplasias , Selenio , Humanos , Selenio/administración & dosificación , Selenio/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Estudios de Casos y Controles , Neoplasias/epidemiología , Neoplasias/etiología , Vietnam/epidemiología , Factores de Riesgo , Anciano , Adulto , Oportunidad Relativa , Dieta/efectos adversosRESUMEN
OBJECTIVES: The aims of this study are to better understand phenotypic differences between male and female rats during sepsis, to characterise the contribution of the beta1-adrenergic blocker landiolol to septic cardiomyopathy and to determine why landiolol induces divergent effects in males and females. METHODS: The myocardial transcriptional profiles in male and female Wistar rats were assessed after the induction of sepsis by cecal ligation and puncture and addition of landiolol. RESULTS: Our results showed major differences in the biological processes activated during sepsis in male and female rats. In particular, a significant decrease in processes related to cell organisation, contractile function, ionic transport and phosphoinositide-3-kinase/AKT (PI3K/AKT) signalling was observed only in males. The transcript of ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 (SERCA3) was sex-differently regulated. In males, landiolol reversed several signalling pathways dysregulated during sepsis. The expression level of genes encoding tubulin alpha 8 (TUBA8) and myosin heavy chain 7B (MYH7) contractile proteins, phosphatase 2 catalytic subunit alpha (PPP2CA), G protein-coupled receptor kinase 5 (GRK5) and A-kinase anchoring protein 6 (AKAP6) returned to their basal levels. In contrast, in females, landiolol had limited effects. CONCLUSION: In males, landiolol reversed the expression of many genes that were deregulated in sepsis. Conversely, sepsis-induced deregulation of gene expression was less pronounced in females than in males, and was maintained in the landiolol-treated females. These findings highlight important sex-related differences and confirm previous observations on the important benefit of landiolol intake on cardiac function in male rats.
RESUMEN
OBJECTIVES: To investigate any gender effect of the beta-1 adrenergic blocker, landiolol, on cardiac performance and energy metabolism in septic rats, and to explore the expression of genes and proteins involved in this process. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female Wistar rats. INTERVENTIONS: One hour after cecal ligation and puncture, male and female rats were randomly allocated to the following groups: sham male, cecal ligation and puncture male, cecal ligation and puncture + landiolol male, sham female, cecal ligation and puncture female, and cecal ligation and puncture + landiolol female. Cardiac MRI was carried out 18 hours after cecal ligation and puncture to assess in vivo cardiac function. Ex vivo cardiac function measurement and P magnetic resonance spectroscopy were subsequently performed using an isovolumic isolated heart preparation. Finally, we assessed cardiac gene and protein expression. MEASUREMENTS AND MAIN RESULTS: In males, landiolol increased indexed stroke volume by reversing the indexed end-diastolic volume reduction without affecting left ventricle ejection fraction. In females, landiolol did not increase indexed stroke volume and indexed end-diastolic volume but decreased left ventricle ejection fraction. Landiolol had no effect on ex vivo cardiac function and on high-energy phosphate compounds. The effect of landiolol on the gene expression of natriuretic peptide receptor 3 and on protein expression of phosphorylated-AKT:AKT ratio and endothelial nitric oxide synthase was different in males and females. CONCLUSIONS: Landiolol improved the in vivo cardiac performance of septic male rats while deleterious effects were reported in females. Expression of natriuretic peptide receptor 3, phosphorylated-AKT:AKT, and endothelial nitric oxide synthase are signaling pathways to investigate to better understand the sex differences in sepsis.