Objective The predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable coronary artery disease (SCAD) in the drug-eluting stent era is not yet clear. We aimed to evaluate the prognostic value of NT-proBNP in SCAD patients after percutaneous coronary intervention (PCI).Methods We examined 4, 293 consecutive SCAD patients who underwent PCI between January 2013 and December 2013 in Fuwai Hospital, China. The primary endpoint was all-cause death. NT-proBNP levels were measured before PCI using Elisa kits (Biomedica, Austria). The indication for PCI was based on the degree of coronary stenosis and evidence of ischemia.Results Among 3, 187 SCAD patients with NT-proBNP data, after a 2-year follow-up, NT-proBNP levels were predictive for all-cause death in the SCAD population[area under the receiver operating characteristic curve, 0.768; 95% confidence interval (CI), 0.687-0.849; P < 0.001]. At the optimum cutoff point of 732 pg/mL, the sensitivity and specificity of death was 75.0% and 72.3%, respectively. In a multivariable Cox regression model, the death hazard ratio was 6.43 (95% CI, 2.99-13.82; P < 0.001) for patients with NT-proBNP levels ≥ 732 pg/mL, compared with < 732 pg/mL.Conclusion NT-proBNP is a strong predictor of 2-year death with SCAD after PCI in the drug-eluting stent era.
Objective Autophagy is a highly conserved intracellular degradation pathway. Many picornaviruses induce autophagy to benefit viral replication, but an understanding of how autophagy occurs remains incomplete. In this study, we explored whether coxsackievirus B3 (CVB3) infection induced autophagy through endoplasmic reticulum (ER) stress.Methods In CVB3-infected HeLa cells, the specific molecules of ER stress and autophagy were detected using Western blotting, reverse transcription polymerase chain reaction (RT-PCR), and confocal microscopy. Then PKR-like ER protein kinase (PERK) inhibitor, inositol-requiring protein-1 (IRE1) inhibitor, or activating transcription factor-6 (ATF6) inhibitor worked on CVB3-infected cells, their effect on autophagy was assessed by Western blotting for detecting microtubule-associated protein light chain 3 (LC3).Results CVB3 infection induced ER stress, and ER stress sensors PERK/eIF2α, IRE1/XBP1, and ATF6 were activated. CVB3 infection increased the accumulation of green fluorescent protein (GFP)-LC3 punctuation and induced the conversion from LC3-Ⅰ to phosphatidylethanolamine-conjugated LC3-1 (LC3-Ⅱ). CVB3 infection still decreased the expression of mammalian target of rapamycin (mTOR) and p-mTOR. Inhibition of PERK, IRE1, or ATF6 significantly decreased the ratio of LC3-Ⅱ to LC3-Ⅰ in CVB3-infected HeLa cells.Conclusion CVB3 infection induced autophagy through ER stress in HeLa cells, and PERK, IRE1, and ATF6a pathways participated in the regulation of autophagy. Our data suggested that ER stress may inhibit mTOR signaling pathway to induce autophagy during CVB3 infection.
Objective To determine the mitigating effects of sodium 4-phenylbutyrate (4-PBA) on high-fat diet (HFD)-induced spermatogenesis dysfunction.Methods Male rats (n=30) were randomly divided into three groups:control, HFD, and 4-PBA (HFD +4-PBA). After 13 weeks, rats were euthanized. Testes and epididymis were harvested for further analysis. Sex hormones were detected, and hematoxylin and eosin staining was performed to examine the histological changes in the testes. Semen samples were collected to evaluate sperm quality. Spermatogenic cell apoptosis was detected by TUNEL assay.Results Compared with the control group, the final body weight and body weight gain were significantly higher in HFD-fed rats, while the testicle/body weight ratios were lower (P < 0.05). In HFD-fed rats, obvious pathological changes in the testicular tissue were observed. Treatment with 4-PBA attenuated HFD-induced histological damage, ameliorated the HFD-induced decrease in serum testosterone (T), and reduced the rate of testicular cell apoptosis (P < 0.05) in obese male rats. Finally, 4-PBA significantly improved semen parameters in HFD rats (P < 0.05).Conclusion HFD exposure induced detrimental effects on spermatogenesis, semen quality, serum T level, and testicular cell apoptosis in rats. Treatment with 4-PBA ameliorated HFD induced impaired spermatogenesis via inhibition of apoptosis in rats. 4-PBA may have therapeutic value in the treatment of obesity related impairment of spermatogenesis.
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