Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease with high mortality, and the mean age at morbidity is younger than in other types of stroke. Early brain injury (EBI) plays a key role in the poor prognoses of SAH. In EBI, multiple forms of cell death have been identified and well studied; however, the role of ferroptosis has not been elucidated. Hence, in this study, we developed an in vivo (SAH rat model) and in vitro model (SH-SY5Y oxyhemoglobin injury model) to understand the role of ferroptosis in EBI, then explored the protective mechanism of ferrostatin-1 (Fer-1). Firstly, we found that neurological scores, blood–brain barrier permeability, brain edema deteriorated after SAH in the in vivo model, cell viability was decreased after SAH in both cortex and SH-SY5Y cells. Further, iron content in cortex was increased after SAH, while transferrin receptor 1 and ferroportin (Fpn) were increased in oxyhemoglobin-treated in vitro model. Additionally, glutathione content and glutathione peroxidase 4 activity were reduced in SAH rats, and lipid peroxides were increased in the oxyhemoglobin-treated cells. Finally, administration of Fer-1 upregulated Fpn and decreased the iron content, then improved the lipid peroxidation and EBI. However, Fer-1 had no effect on the apoptosis. Our study indicated that the ferroptosis was involved in EBI of SAH, and the inhibitor Fer-1 provided neuroprotection against EBI by alleviating ferroptosis, the potential protective mechanism might be via suppressing lipid peroxidation.
To investigate the association between ultrasonically detected fetal urinary system abnormalities and chromosomal copy number variations (CNVs) in Heilongjiang Province, northeastern China. Cohort study: 183 fetuses with ultrasound-detected urinary system anomalies (invasive prenatal diagnosis, 2017.01–2025.09, Second Affiliated Hospital of Harbin Medical University) were enrolled. All underwent CNV analysis: 21 without karyotyping, 12 with abnormal karyotypes, 150 with normal karyotypes. The 150 normal-karyotype cases were split into isolated CAKUT (63, 42
Autism Spectrum Disorder (ASD) pathogenesis remains unclear, with mitochondrial dysfunction implicated as a key contributor. Reliable mitochondrial-related diagnostic biomarkers are lacking, hindering early detection and mechanistic studies. This study integrated transcriptomic data from postmortem ASD cortical tissues (GSE28521 for training; GSE64018 for validation) with mitochondrial-related genes (MRGs) from MitoCarta3.0. Mitochondrial pathways were investigated using gene set enrichment analysis (GSEA). Candidate ASD-mitochondria (ASD-MIT) genes were identified by combining differential expression analysis, weighted gene co-expression network analysis (WGCNA), and MRGs. Machine learning algorithms (LASSO, Random Forest, and SVM-RFE) were applied to screen hub genes. Diagnostic performance was evaluated using a linear predictive model, an artificial neural network (ANN), and a nomogram. Single-sample GSEA (ssGSEA) was used to assess associations between hub genes and mitochondrial pathway activity. Biological validation included qPCR in BTBR mice and protein localization analysis using the Human Protein Atlas (HPA). GSEA revealed significant downregulation of mitochondrial pathways in ASD. 22 candidate ASD-MIT genes were identified, from which three hub genes—IDH3A, MRPL2, and CHCHD4—were consistently selected by all three machine learning models. The three-gene panel demonstrated strong diagnostic ability (AUC = 0.910), confirmed by the ANN model (AUC = 0.903). The nomogram achieved excellent predictive accuracy (C-index = 0.964). Importantly, ssGSEA analysis showed that these genes were strongly associated with mitochondrial pathway activity, particularly mitochondrial calcium ion transport. qPCR validated significant downregulation of Idh3a and Mrpl2 in BTBR mice, and HPA confirmed mitochondrial localization and brain expression. This study identifies a mitochondrial gene signature associated with ASD and highlights IDH3A, MRPL2, and CHCHD4 as promising diagnostic biomarkers. These findings advance understanding of mitochondrial dysfunction in ASD pathogenesis and further suggest that disruption of mitochondrial Ca2⁺–energy coupling may represent a key mechanistic feature of the disease.
Intestinal barrier function protection is essential to ameliorate sepsis. Isoliquiritin (ILQ) is a natural compound with broad biological activities. However, whether ILQ attenuates sepsis-induced intestinal damage remains unclear. An LPS-induced sepsis mouse model was established. ILQ inhibited body weight loss in sepsis mice. ILQ enhanced mouse intestinal function, as evidenced by decreased serum LDH levels and increased citrulline levels. Alcian blue staining showed that ILQ increased goblet cells in sepsis mouse ileum. ILQ increased the MUC2 RNA levels and decreased the claudin-2 protein expression in the sepsis mouse ileum. We subsequently examined the ILQ effects on intestinal autophagy activity. ILQ reduced the p62 protein expression and increased the conversion of LC3BI to LC3BII in sepsis mouse ileum. The LC3 protein expression was reduced in sepsis mouse ileum. An LPS-stimulated Caco-2 cell model was established. ILQ enhanced the viability of LPS-stimulated Caco-2 cells, reduced the LDH activity in cell supernatants, and increased the MUC2 RNA levels. ILQ enhanced the cellular barrier of LPS-stimulated Caco-2 cells, as indicated by the reduction in claudin-2 protein and the increase in TEER. ILQ also promoted autophagy activity in LPS-stimulated Caco-2 cells. Rescue experiments showed that an autophagy inhibitor disrupts the protective effect of ILQ on the Caco-2 cell barrier and inhibits ILQ-promoted autophagy activity. ILQ promoted the expression of LC3BII following the addition of chloroquine in LPS-stimulated Caco-2 cells. In conclusion, ILQ alleviated intestinal dysfunction and promoted autophagy activity in sepsis mice ileum, and might enhance the barrier function of LPS-stimulated Caco-2 cells via autophagy.
BACKGROUND:Depressive and anxiety disorders constitute a major component of the disease burden of mental disorders in China. AIMS:To comprehensively evaluate the disease burden of depressive and anxiety disorders in China. METHOD:The raw data is sourced from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021. This study presented the disease burden by prevalence and disability-adjusted life years (DALYs) of depressive and anxiety disorders at both the national and provincial levels in China from 1990 to 2021, and by gender (referred to as 'sex' in the GBD 2021) and age. RESULTS:From 1990 to 2021, the number of depressive disorder cases (from 34.4 to 53.1 million) and anxiety disorders (from 40.5 to 53.1 million) increased by 54% (95% uncertainty intervals: 43.9, 65.3) and 31.2% (19.9, 43.8), respectively. The age-standardised prevalence rate of depressive disorders decreased by 6.4% (2.9, 10.4), from 3071.8 to 2875.7 per 100 000 persons, while the prevalence of anxiety disorders remained stable. COVID-19 had a significant adverse impact on both conditions. There was considerable variability in the disease burden across genders, age groups, provinces and temporal trends. DALYs showed similar patterns. CONCLUSION:The burden of depressive and anxiety disorders in China has been rising over the past three decades, with a larger increase during COVID-19. There is notable variability in disease burden across genders, age groups and provinces, which are important factors for the government and policymakers when developing intervention strategies. Additionally, the government and health authorities should consider the potential impact of public health emergencies on the burden of depressive and anxiety disorders in future efforts.
