An innovative predictive model for cervical cancer constructed around a gene profile associated with cholesterol metabolism.

Cholesterol metabolism is crucial for cell survival and cancer progression. The prognostic patterns of genes linked to cholesterol metabolism (CMAGs) in CESC, however, have received very little attention in research. From public databases, TCGA-CESC cohorts with mRNA expression patterns and the accompanying clinical information of patients were gathered. Consensus clustering was used to find the molecular subtype connected to cholesterol metabolism. In the TCGA-CESC cohort, a predictive risk model with 28 CMAGs was created using Lasso-Cox regression. The function enrichment analysis between groups with high-and low-risk were investigated by employing GO, KEGG, and GSVA software. The immune cell infiltration was analyzed using ESTIMATE, CIBERSORT, and MCPCOUNTER methods. Finally, we select 7 genes in risk model for further multivariate Cox analysis, and ultimately a hub gene, CHIT1, was identified. Meanwhile, the function of CHIT1 was preliminarily verified in cell and mice tumor model. In conclusion, the abundance of the CHIT1 gene might be beneficial for forecasting the prognosis of CESC, demonstrating that cholesterol metabolism could be a promising treatment target for CESC.

Demethylnobiletin ameliorates cerebral ischemia-reperfusion injury in rats through Nrf2/HO-1 signaling pathway.

BACKGROUND: Demethylnobiletin (DN), with a variety of biological activities, is a polymethoxy-flavanone (PMF) found in citrus. In the present study, we explored the biological activities and potential mechanism of DN to improve cerebral ischemia reperfusion injury (CIRI) in rats, and identified DN as a novel neuroprotective agent for patients with ischemic brain injury. METHODS: Rat CIRI models were established via middle cerebral artery occlusion (MCAO). Primary nerve cells were isolated and cultured in fetal rat cerebral cortex in vitro, and oxygen-glucose deprivation/reperfusion (OGD/R) models of primary nerve cells were induced. After intervention with DN with different concentrations in MCAO rats and OGD/R nerve cells, 2,3,5-triphenyltetrazolium chloride staining was used to quantify cerebral infarction size in CIRI rats. Modified neurological severity score was utilized to assess neurological performance. Histopathologic staining and live/dead cell-viability staining was used to observe apoptosis. Levels of glutathione (GSH), superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in tissues and cells were detected using commercial kits. DN level in serum and cerebrospinal fluid of MCAO rats were measured by liquid chromatography tandem mass spectrometry. In addition, expression levels of proteins like Kelch like ECH associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nfr2) and heme oxygenase 1 (HO-1) in the Nrf2/HO-1 pathway, and apoptosis-related proteins like Cleaved caspase-3, BCL-2-associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) were determined by Western blot and immunofluorescence. RESULTS: DN can significantly enhance neurological function recovery by reducing cerebral infarction size and weakening neurocytes apoptosis in MCAO rats. It was further found that DN could improve oxidative stress (OS) injury of nerve cells by bringing down MDA and ROS levels and increasing SOD and GSH levels. Notably, DN exerts its pharmacological influences through entering blood-brain barrier. Mechanically, DN can reduce Keap1 expression while activate Nrf2 and HO-1 expression in neurocytes. CONCLUSIONS: The protective effect of DN on neurocytes have been demonstrated in both in vitro and in vivo circumstances. It deserves to be developed as a potential neuroprotective agent through regulating the Nrf2/HO-1 signaling pathway to ameliorate neurocytes impairment caused by OS.