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The results also revealed that four non-coding RNAs (cicRNA.20127, mmu_circ_0012936, ENSMUST00000194077 and NONMMUT109267) may influence glutathione metabolism. Additionally, 44 DEcircRNAs and 7 DElncRNAs were found to possess coding potential. These findings provide clues to the molecular pathways through which Nrf2 protects neurons.Vascular dementia (VD) is a common disease that occurs during human aging. Gastrodin (GAS) has potential benefits for the prevention and treatment of VD. In the present study, we investigated the effects of GAS on cognitive dysfunction in rats with VD induced by permanent middle cerebral artery occlusion (pMCAO) and explored the underlying mechanism. Immunohistochemical and western blot analyses revealed that GAS attenuated hippocampal levels of LC3 (microtubule-associated protein 1 light chain 3), p62, and phosphorylated CaMKII (Ca2+-calmodulin stimulated protein kinase II) in VD rats. Additionally, our results revealed that cobalt chloride blocked autophagic flux in HT22 cells, which was confirmed by increased levels of LC3 and p62 when combined with chloroquine. Notably, GAS ameliorated the impaired autophagic flux. Furthermore, we confirmed that GAS combined with KN93 (a CaMKII inhibitor) or CaMKII knockdown did not impact the reduced p62 levels when compared with GAS treatment alone. Furthermore, a co-immunoprecipitation assay demonstrated that endogenous p62 bound to CaMKII, as confirmed by mass spectrometric analysis after the immunoprecipitation of p62 from HT22 cells. These findings revealed that GAS attenuated autophagic flux dysfunction by inhibiting the Ca2+/CaMKII signaling pathway to ameliorate cognitive impairment in VD.Lung cancer morbidity and mortality remain the leading causes of tumor-associated death worldwide. The discovery of early diagnostic and prognostic markers of lung cancer could significantly improve the survival rate and decrease the mortality rate. FPN1 is the only known mammalian iron exporter. However, the molecular and biological functions of FPN1 in lung cancer remain unclear. Here, FPN1 mRNA expression in lung cancer was estimated using the TCGA, Oncomine, TIMER, and UALCAN databases. The prognostic role of FPN1 was evaluated using Kaplan-Meier plotter and PrognoScan. Associations between FPN1 and immune infiltration in lung cancer were evaluated by the TIMER and CIBERSORT algorithms. FPN1 mRNA and protein expressions were significantly downregulated in lung cancer. Low FPN1 expression was strongly related to worse prognosis in patients with lung cancer. GO and KEGG analyses and GSEA suggested that FPN1 was remarkably related to iron homeostasis and immunity. Importantly, FPN1 was remarkably associated with the infiltrating abundance of multiple immune cells. Moreover, FPN1 displayed a strong correlation with various immune marker sets. We investigated the clinical application value of FPN1 and provided a basis for the sensitive diagnosis, prognostication and targeted therapy of lung cancer.Primary open angle glaucoma (POAG) is the leading cause of irreversible blindness. Dysfunction of the trabecular meshwork (TM), resulting in decreased outflow of aqueous humor and increased intraocular pressure (IOP), plays an important role in the pathogenesis of POAG. However, the underlying mechanisms still remain unclear. In this study, we demonstrated that the eIF2-α/ATF4/CHOP branch of unfolded protein response (UPR) was activated in human trabecular meshwork cells (HTMCs) upon tert-butyl hydroperoxide (TBHP) exposure. Inhibition of ATF4 ameliorated TBHP-induced apoptosis and inflammatory cytokine production, while ectopic expression of ATF4 increased the expression of endothelial leukocyte adhesion molecule (ELAM)-1 and IL-8 in HTMCs. Furthermore, we found that ATF4 inhibition reduced tunicamycin-induced caspase-3 activation, ROS production, ELAM-1 expression, and HTMCs phagocytosis impairment. By an in vivo study in mice, we showed that overexpression of ATF4 in the TM induced C/EBP homologous protein (CHOP) expression and TM cells apoptosis, contributing to inflammatory cytokine production, and probably IOP elevation. More importantly, upregulation of ATF4 and CHOP, and colocalization of ATF4 with ELAM-1 were found in the TM of POAG patients. These results suggest that ATF4 is a critical mediator of oxidative stress and ER stress-induced TM cell dysfunction and apoptosis in POAG.Antiarrhythmic drug therapy (ADT) and catheter ablation (CA) are the main treatments for paroxysmal atrial fibrillation. However, the short- and long-term clinical efficacy of these treatments remains controversial. Our goal is to investigate efficacy and safety of the standardized treatment of elderly patients with paroxysmal atrial fibrillation (PAF). Eight randomized controlled trials on CA and ADT for treating PAF were included. Totally, 1336 patients were included. Nintedanib chemical structure Studies on CA and ADT for treating PAF that were published between January 2005 and June 2020 in the Cochrane Library, PubMed and EMBASE were screened and identified. Atrial fibrillation-free rates and Short Form (SF-36) health score-related indexes were analyzed. Atrial fibrillation-free rates were similar in the CA and ADT groups [risk ratio (RR) 1.32; 95% confidence interval (CI) 0.96-1.82; P = 0.08] at 3 months. The CA group had a significantly higher atrial fibrillation-free rate at 6 months (RR 1.87; 95% CI 1.38-2.53; P less then 0.001), 9 months (RR 2.38; 95% CI 1.43-3.96; P less then 0.001), and 12 months (RR 2.21; 95% CI 1.28-3.84; P=0.005). However, there was no significant difference in terms of long-term efficacy at 24 months (RR 1.81; 95% CI 0.97-3.36; P = 0.06). The 12-month QOL physical and mental components (RR 2.41; 95% CI 0.89-3.93; P = 0.002) were significantly higher in CA group. The CA is more effective than ADT in the short-term prognosis. But the long-term prognosis of PAF needs to be verified via randomized controlled trials with longer follow-up durations.Radiation therapy is an effective method in the management of esophageal cancer. MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. However, the roles of specific miRNAs in radioresistant esophageal cancer remain to be investigated. In present study, the relative expression level of miR-20b-5p and miR-125a-5p were evaluated by quantitative Real-time polymerase chain reaction. Cell counting Kit-8 assay, wound-healing assay, transwell assay were used to assess cell proliferation, cell migration and cell invasion. TUNEL and Annexin V-FITC assays were applied to evaluate cell apoptosis. Dual-luciferase reporter gene assay was conducted to identify direct targets of miRNAs. The protein expression level was assessed by Western blot. The results indicated that miR-20b-5p was increased in radioresistant KYSE-150R cells compared with KYSE-150 cells, whereas miR-125a-5p was downregulated. MiR-20b-5p upregulation promoted cell proliferation, migration, invasion, and the EMT process, and decreased apoptosis by negatively regulating PTEN. MiR-125a-5p inhibited cell proliferation, migration, invasion, the EMT process and it induced apoptosis by negatively regulating IL6R. These data indicate that miR-20b-5p and miR-125a-5p promote tumorigenesis in radioresistant KYSE-150R cells and have the potential to be used as novel therapeutic targets for the treatment of esophageal cancer.The degree of retinal fibrosis increased in proliferative diabetic retinopathy (PDR) patients after administration of anti-Vascular endothelial growth factor (VEGF) injections. Previous studies showed that the balance between connective tissue growth factor (CTGF) and VEGF plays an important role. Therefore, in a high-glucose state, an anti-VEGF and CTGFshRNA dual-target model was used to simulate clinical dual-target treatment in PDR patients, and RNA sequencing (RNA-Seq) technology was used for whole transcriptome sequencing. A hypoxia model was constructed to verify the sequencing results at the cellular level, and the vitreous humor and proliferative membranes were collected from patients for verification. All sequencing results included Follistatin-like protein 1 (FSTL1) and extracellular matrix (ECM) receptor pathway, indicated that anti-VEGF therapy may upregulate FSTL1 expression, while dual-target treatment downregulated FSTL1. Thus, we further studied the function of FSTL1 on the expression of VEGF and ECM factors by both overexpressing and silencing FSTL1. In conclusion, our results suggested that FSTL1 may be involved in the pathogenesis of PDR and is related to fibrosis caused by the anti-VEGF treatment, thus providing a potential target for gene therapy in PDR.

Early diagnosis of severe acute pancreatitis (SAP) is essential to minimize its mortality and improve prognosis. We aimed to develop an accurate and applicable machine learning predictive model based on routine clinical testing results for stratifying acute pancreatitis (AP) severity.

We identified 11 markers predictive of AP severity and trained an AP stratification model called APSAVE, which classified AP cases within 24 hours at an average area under the curve (AUC) of 0.74 +/- 0.04. It was further validated in 568 validation cases, achieving an AUC of 0.73, which is similar to that of Ranson's criteria (AUC = 0.74) and higher than APACHE II and BISAP (AUC = 0.69 and 0.66, respectively).

We developed and validated a venous blood marker-based AP severity stratification model with higher accuracy and broader applicability, which holds promises for reducing SAP mortality and improving its clinical outcomes.

Nine hundred and forty-five AP patients were enrolled into this study. Clinical venous blood tests covering 65 biomarkers were performed on AP patients within 24 hours of admission. An SAP prediction model was built with statistical learning to select biomarkers that are most predictive for AP severity.

Nine hundred and forty-five AP patients were enrolled into this study. Clinical venous blood tests covering 65 biomarkers were performed on AP patients within 24 hours of admission. An SAP prediction model was built with statistical learning to select biomarkers that are most predictive for AP severity.Living in adverse neighborhood environments has been linked to risk of aging-related diseases and mortality; however, the biological mechanisms explaining this observation remain poorly understood. DNA methylation (DNAm), a proposed mechanism and biomarker of biological aging responsive to environmental stressors, offers promising insight into potential molecular pathways. We examined associations between three neighborhood social environment measures (poverty, quality, and social cohesion) and three epigenetic clocks (Horvath, Hannum, and PhenoAge) using data from the Detroit Neighborhood Health Study (n=158). Using linear regression models, we evaluated associations in the total sample and stratified by sex and social cohesion. Neighborhood quality was associated with accelerated DNAm aging for Horvath age acceleration (β = 1.8; 95% CI 0.4, 3.1), Hannum age acceleration (β = 1.7; 95% CI 0.4, 3.0), and PhenoAge acceleration (β = 2.1; 95% CI 0.4, 3.8). In models stratified on social cohesion, associations of neighborhood poverty and quality with accelerated DNAm aging remained elevated for residents living in neighborhoods with lower social cohesion, but were null for those living in neighborhoods with higher social cohesion.