Sulforaphane alleviates the meiosis defects induced by 3-nitropropionic acid in mouse oocytes.

3-Nitropropionic acid (3-NP) is a mycotoxin commonly found in plants and fungi that has been linked to mammalian intoxication. Previously, we found 3-NP treatment exhibited reproductive toxicity by inducing oxidative stress in mouse ovary; however, the toxic effects of 3-NP on mouse oocyte maturation have not been investigated. Sulforaphane (SFN) is a naturally bioactive phytocompound derived from cruciferous vegetables that has been shown to possess cytoprotective properties. The present study was designed to investigate the cytotoxicity of 3-NP during mouse oocyte maturation and the protective effects of SFN on oocytes challenged with 3-NP. The results showed 3-NP had a dose-dependent inhibitory effect on oocyte maturation, and SFN significantly alleviated the defects caused by 3-NP, including failed first polar body extrusion and abnormal spindle assembly. Furthermore, 3-NP caused abnormal mitochondrial distribution in oocytes and disrupted mitochondrial functions, including mitochondrial depolarization, decreased ATP levels, and increased mitochondrial-derived ROS. Finally, 3-NP induced oxidative stress in oocytes, leading to increased apoptosis and autophagy, while SFN supplementation had significant cytoprotective effects on these damages. Collectively, our results provide insight on the mechanism of 3-NP toxicity in mouse oocytes and suggest the application of SFN may be a viable intervention strategy to mitigate 3-NP-induced reproductive toxicity.

Serum tumor markers for the prediction of concordance between genomic profiles from liquid and tissue biopsy in patients with advanced lung adenocarcinoma.

BACKGROUND: The concordance between mutations detected from plasma and tissue is critical for treatment choices of patients with advanced lung adenocarcinoma. METHODS: We prospectively analyzed the association of the serum tumor markers with the concordance between blood and tissue genomic profiles from 185 patients with advanced lung adenocarcinoma. The concordance was defined according to 3 criteria. Class 1 included all targetable driver mutations in 8 genes; class 2 included class 1 mutations plus mutations in KRAS, STK11, and TP53; class 3 included class 2 mutations plus tumor mutation burden (TMB) status. RESULTS: Collectively, 150 out of 185 patients had mutations in both tissue and plasma samples, while one patient was mutation-negative for both, resulting a concordance of 81.6%. The concordance rate for class 1 mutations was 80%, and 65% and 69% for class 2 and class 3, respectively. Carbohydrate antigen 19-9 (CA19-9) or cytokeratin 19 (CYFRA21-1) levels higher than the normal upper limit predicted the concordance of tissue and blood results in class 1 (P=0.005, P=0.011), class 2 (P=0.011, P<0.001), and class 3 (P=0.001, P=0.014). In class 1, the cutoff values of CA19-9 were 30, 36, and 284 U/mL to reach the concordance thresholds of 90%, 95%, and 100%, respectively (P=0.032, P=0.003, P=0.043). For CYFRA21-1, the cutoff values were 6, 18, and 52 µg/L (P=0.005, P=0.051, P=0.354). In class 2, the cutoff values for CYFRA21-1 were 18, 22, and 52 µg/L (P=0.001, P=0.001, P=0.052). In class 3, the cutoff values for CA19-9 were 36, 39, and 85 U/mL (P=0.003, P=0.001, P=0.008). For CYFRA21-1, the cutoff values were 22, 52, and 52 µg/L (P=0.900, P>0.99, P>0.99). When the sum score for 4 serum tumor markers was greater than 35, both class 1, class 2, and class 3 reached a predictive threshold of 90%. CONCLUSIONS: Serum tumor markers can be used as easy and practical clinical predictors of concordance in mutation profiles between blood and tissue samples from patients with advanced lung adenocarcinoma.

Effects of zinc supplementation on the incidence of mortality in preschool children: a meta-analysis of randomized controlled trials.

BACKGROUND: Previous trials have shown that zinc supplementation can decrease the risk of diarrhea, pneumonia, and malaria in children; however, the effects of zinc supplementation on mortality remain unclear. This study aimed at evaluating the benefits and risks of zinc supplementation on both total mortality and cause-specific mortality. METHODOLOGY AND PRINCIPAL FINDINGS: We searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in preschool children reporting total mortality or cause-specific mortality. Relative risk (RR) was used as a measure of the effect of zinc supplementation on the risk of mortality using a random effect model. Of the 1,520 identified articles, we included 8 trials reporting data on 87,854 children. Overall, zinc supplementation had no effect on total mortality (RR, 0.76; 95% CI: 0.56-1.04; P = 0.084), diarrhea-related mortality (RR, 0.80; 95% CI: 0.53-1.20; P = 0.276), pneumonia-related mortality (RR, 0.52; 95% CI: 0.11-2.39; P = 0.399), malaria-related mortality (RR, 0.90; 95% CI: 0.77-1.06; P = 0.196), or other causes of mortality (RR, 0.98; 95% CI: 0.67-1.44; P = 0.917). Subgroup analysis indicated that zinc supplementation was associated with a reduction in total mortality risk if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months. CONCLUSIONS/SIGNIFICANCE: Zinc supplementation does not have an effect on total mortality, diarrhea-related mortality, pneumonia-related mortality, malaria-related mortality, or other causes of mortality. Subgroup analysis suggested that zinc supplementation can effectively reduce the risk of total mortality if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.

Airborne fine particulate matter induced pulmonary inflammation as well as oxidative stress in neonate rats.

BACKGROUND: Airborne fine particulate matter (PM) can induce pulmonary inflammation which may adversely affect human health, but very few reports about its effect on the neonate rats are available. This study aimed to observe the potential impact and toxicity of fine PMs on the airway in neonate rats. METHODS: Pulmonary inflammation, cytotoxicity, histopathology, and antioxidants as well as oxidant products were assessed 24 hours after intratracheal instillation of fine PM consecutively for 3 days. Cytotoxicity of fine PM was measured in HEp-2 cells. RESULTS: Rats treated with high dose fine PM developed significant pulmonary inflammation characterized by neutrophil and macrophage infiltration. The inflammatory process was related to elevated level of TNF-α and prooxidant/antioxidant imbalance in the lung. Cytotoxicity studies performed in human epithelial cells indicated that high dose fine PM significantly reduced cell viability. CONCLUSION: The study demonstrated acute exposure to fine PM induced airway inflammation as well as increased oxidative stress in addition to its direct toxic effect on airway epithelium cells.