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Abstract-Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates, and effective strategies to prevent and treat NEC are still lacking. Studies have shown that N-acetylcysteine (NAC) has protective effects against NEC, however, the specific mechanism underlying its effects on intestinal functions remains unclear. Recently, NAC has been shown to suppress ferroptosis in many diseases, while it is unclear whether the beneficial effects of NAC on NEC are related to ferroptosis. In this study, we revealed that ferroptosis was significantly induced in intestinal samples from infants with NEC. NAC alleviated intestinal inflammation, barrier damage and ferroptosis in multifactorial NEC models in vivo and in vitro. Sestrin2 (SESN2) was identified as an important mediator of NAC-induced ferroptosis resistance in intestinal epithelial cells. Furthermore, SESN2 knockdown inhibited the inflammatory response, alleviated barrier damage and ferroptosis in intestinal epithelial cells and enhanced the protective effects of NAC to a certain extent. Conversely, cells overexpressing SESN2 showed the opposite changes. In summary, our study demonstrated that NAC attenuates NEC progression by decreasing SESN2 expression to inhibit ferroptosis in intestinal epithelial cells, suggesting that NAC might be an effective clinical treatment for NEC.
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Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on neonatal necrotizing enterocolitis (NEC) is not well characterised. This cross-sectional study evaluated the potential effects of pandemic-related measures on NEC morbidity in premature infants in a neonatal ward during the COVID-19 pandemic. Methods: This was a retrospective study conducted in a tertiary neonatal ward in eastern and central China over 6 consecutive years (2017, 2018, 2019, 2020, 2021 and 2022). The medical records of 189 premature infants with stage II or III NEC were reviewed for clinical manifestations and aetiologies. The data were analysed and compared between the prepandemic period (2017, 2018, and 2019) and the pandemic period (2020, 2021 and 2022). Results: A total of 9,903 infants with gestational age (GA) < 37 weeks were enrolled, including 5,382 in the prepandemic period and 4,521 in the pandemic period. A reduction in stage II or III NEC morbidity was observed in infants with GA < 37 weeks, with an average annual morbidity of 2.29% (123/5,382) (95% CI, 1.89%-2.68%) in the prepandemic period and 1.46% (66/4,521) (95% CI, 1.11%-1.81%) in the pandemic period. NEC morbidity showed resurgent characteristics in 2021. When prepandemic coinfections were excluded, most cases of NEC with bloodstream infections in the prepandemic period were attributable to Gram-negative bacteria (27/32, 84.38%), mainly Klebsiella pneumoniae, while in the pandemic period they were attributable to Gram-positive bacteria (10/18, 55.56%), mainly Staphylococcus aureus. Antimicrobial susceptibility testing revealed that Klebsiella pneumoniae was 100% sensitive to meropenem, imipenem, ciprofloxacin and levofloxacin and 100% resistant to ampicillin. Staphylococcus capitis was 100% sensitive to vancomycin, linezolid, tetracycline, cotrimoxazole and cefoxitin and 100% resistant to penicillin and benzathine. Conclusions: COVID-19 pandemic-related interventions can reduce the morbidity of NEC and change the pathogen spectrum in patients with bloodstream infections. We need to understand the exact factors leading to these changes.
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3-chloro-1,2-propanediol (3-MCPD) is a newly discovered food process pollutant with nephrotoxicity. And the mechanism by which 3-MCPD affects male spermatogenesis has not been fully studied. Cell viability, blood-testis barrier (BTB) related protein, progesterone content, reactive oxygen species (ROS) generation, and cell apoptosis were determined by a CCK8 assay, western blot, ELISA, flow cytometry, and TUNEL staining, respectively. Wistar rats were divided into three groups: low-dose 3-MCPD, high-dose 3-MCPD, and control. Sperm parameters, hormonal levels, and biomarkers of oxidative stress in the testis and epididymis were detected by ELISA. Multiple molecular experiments including molecular docking and western blot were used to elucidate the underlying mechanisms. 3-MCPD affects testicular cell activity, and promotes ROS production and apoptosis. Disrupting the integrity of BTB in the body, downregulating sex hormones and sperm quality, and promoting apoptosis. 3-MCPD may function through CYP2C9. This study preliminarily explores the mechanism by which 3-MCPD affects spermatogenesis. It was found that 3-MCPD destroys the structure and function of BTB and damages the testicular function of male mice, thus affecting the process of spermatogenesis via CYP2C9.
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OBJECTIVE: This study aimed to evaluate the role of receptor-interacting protein kinase-3 (RIPK3) in the diagnosis, estimation of disease severity, and prognosis of premature infants with necrotising enterocolitis (NEC). METHODS: RIPK3, lactic acid (LA), and C-reactive protein (CRP) levels were measured in the peripheral blood of 108 premature infants between 2019 and 2023, including 24 with stage II NEC, 18 with stage III NEC and 66 controls. Diagnostic values of the indicators for NEC were evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: Plasma RIPK3 and LA levels upon NEC suspicion in neonates with stage III NEC were 32.37 ± 16.20 ng/mL. The ROC curve for the combination of RIPK3, LA, CRP for NEC diagnosis were 0.925. The time to full enteral feeding (FEFt) after recovery from NEC was different between two expression groups of plasma RIPK3 (RIPK3 < 20.06 ng/mL and RIPK3 ≥ 20.06 ng/mL). CONCLUSION: Plasma RIPK3 can be used as a promising marker for the diagnosis and estimation of disease severity of premature infants with NEC and for the guidance on proper feeding strategies after recovery from NEC.