Objective Evidence is lacking regarding the combined effects of smoking and obesity on mortality from coronary heart disease in male veterans. This study aimed to explore the combined effect of smoking and obesity on coronary heart disease mortality in male veterans in China.Methods A cohort of 1,268 male veterans from 22 veteran centers in Xi’an (Shaanxi Province, China) were followed up once every 2 years from February 1, 1987 to October 30, 2016. The endpoint was death from any cause. The hazard ratio (HR) of each risk factor and the 95% confidence interval (CI) were calculated using a multivariate Cox proportional hazard model.Results The total follow-up was 24394.21 person-years; each subject was followed up for a mean duration of 19.24 years. By the end of the study, of the 1,268 veterans, 889 had died, 363 were alive, and 16 were lost to follow-up. Cox regression analysis results revealed that current smoking (HR: 1.552, 95% CI: 1.074–2.243), obesity (HR: 1.625, 95% CI: 1.024–2.581), and the combined effect of the two factors (HR: 2.828, 95% CI: 1.520–5.262) were associated with coronary heart disease mortality.Conclusion Our results suggest that obese veterans who smoke might be an important target population for coronary heart disease mortality control.
Objective To investigate involvement of the aryl hydrocarbon receptor (AhR) in the immunomodulatory effects of cadmium (Cd).Methods The effect of Cd on AhR activation (CYP1A1 and CYP1B1 mRNA expression) was examined in lung leukocytes of Cd-exposed rats (5 and 50 mg/L, 30 d orally) and by in vitro leukocyte exposure. The involvement of AhR signaling in the effects of Cd on the interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) lung leukocyte response was investigated in vitro using the receptor antagonist CH-223191.Results Cd increased CYP1B1 (in vivo and in vitro) and CYP1A1 (in vitro) mRNA, indicating AhR involvement in the action of Cd. In response to Cd, lung leukocytes increased IL-6 and decreased TNF at the gene expression and protein levels, but decreased IL-1β production due to reduced NLRP3. The AhR antagonist CH-223191 abrogated the observed effects of Cd on the cytokine response. The absence of AhR reactivity and cytokine response to Cd of leukocytes from the lungs of a rat strain that is less sensitive to Cd toxicity coincided with a high AhR repressor mRNA level. Conclusion AhR signaling is involved in the lung leukocyte proinflammatory cytokine response to Cd. The relevance of the AhR to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.
Objective Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries. Methods Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca2+ distribution, inositol 1,4,5-trisphosphate receptor (IP3R) abundance, and the activities of voltage-gated K+ channels (KV) and Ca2+-activated K+ channels (BKCa) were examined in rat cerebral vascular smooth muscle cells (VSMCs). Results An increase of cytoplasmic Ca2+ and a decrease of mitochondrial/sarcoplasmic reticulum (SR) Ca2+ were observed in HU rat cerebral VSMCs. The abundance of fusion proteins (mitofusin 1/2 [MFN1/2]) and fission proteins (dynamin-related protein 1 [DRP1] and fission-mitochondrial 1 [FIS1]) was significantly downregulated and upregulated, respectively in HU rat cerebral VSMCs. The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats, and IP3R protein/mRNA levels were significantly upregulated. The current densities and open probabilities of KV and BKCa decreased and increased, respectively. Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1. It also decreased IP3R expression levels and restored the activities of the KV and BKCa channels. MitoTEMPO restored the Ca2+ distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries. Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
Objective Cervical cancer (CC) is one of the most common malignant tumors in gynecology. This study aimed to investigate the prognostic significance of serum microRNA (miR)-378a-3p in CC and the effect of miR-378a-3p on tumor growth.Methods Real-time quantitative polymerase chain reaction analysis was used to measure the expression of miR-378a-3p in serum from patients with CC and healthy control subjects as well as from CC tissues and adjacent normal tissues. The association between serum miR-378a-3p levels and clinicopathological factors was analyzed. The correlation between miR-378a-3p levels and overall survival (OS) of CC patients was determined by Kaplan-Meier analysis. The CC cell proliferation and migration abilities after transfection of miR-378a-3p mimics were detected by Cell Counting Kit-8 and scratch wound healing assays, respectively. Tumor volume and weight in mice treated with miR-378a-3p were measured using a caliper and an electronic balance.Results MiR-378a-3p expression was downregulated in the serum and tissues of CC patients compared to that in healthy control subjects and normal tissues, respectively. Low expression of miR-378a-3p was positively correlated with large tumor size, advanced tumor stage, and lymph node metastasis. The OS of patients with low expression of miR-378a-3p was significantly lower than that of patients with high expression. Overexpression of miR-378a-3p suppressed the proliferation and migration of CC cells. In vivo studies indicated that overexpression of miR-378a-3p was associated with decreased tumor volume and weight in mice.Conclusion MiR-378a-3p downregulation is associated with the development and prognosis of CC, suggesting that it may be a potential biomarker for CC.