Hyperforin regulates renal fibrosis via targeting the PI3K-AKT/ICAM1 axis.

OBJECTIVE: To explore the role and mechanism of hyperforin (one of the active components of Sophora flavescens) in renal fibrosis. METHODS: The active compounds and target proteins of Sophora flavescens were first screened through TCMSP (https://tcmsp-e.com/). The renal fibrosis-related genes were analyzed through GeneCards (https://www.genecards.org/). The differentially expressed genes (DEGs) in renal fibrosis in GEO dataset GSE156181 were obtained. Metascape was applied for target protein enrichment analysis. TGF-ß1-stimulated renal tubular epithelial cells were used for renal fibrosis cell model establishment. The unilateral ureteral obstruction (UUO) mouse model was used for the renal fibrosis in vivo model. Cell viability was detected using an MTT assay. Immunofluorescence staining was employed to detect cell morphology changes and the expression of α-SMA and collagen I. Hematoxylin and eosin (H&E) and Masson staining were employed to determine the renal morphologic change. qRT-PCR or Western blotting was applied to determine the expression levels of the target proteins. RESULTS: After intersecting the analysis results of TCMSP, GeneCards, and dataset GSE156181, hyperforin targeting ICAM1 was identified. Metascape pathway enrichment analysis results revealed that the effective compounds of Sophora flavescens were tightly associated with extracellular matrix (ECM) remodeling and inflammatory response. MTT assay demonstrated that hyperforin had no toxic effect on cells. Immunofluorescence staining results evidenced that hyperforin could partially restore TGF-ß1-induced epithelial-mesenchymal transition (EMT), the PI3K/AKT pathway activation, and ICAM1 upregulation, and these effects of hyperforin could be reversed by ICAM1 overexpression. While the PI3K/AKT pathway activator IGF-1 effectively reversed the EMT inhibition effect of hyperforin on renal tubular epithelial cells. Moreover, the UUO mouse model further confirmed that hyperforin reduced renal fibrosis. CONCLUSION: Hyperforin inhibited renal fibrosis via the PI3K/AKT/ICAM1 axis.

Factors associated with anxiety and depression in patients with erectile dysfunction: a cross-sectional study.

BACKGROUND: Few studies have investigated factors associated with anxiety and depression among patients with erectile dysfunction (ED). This study aimed to investigate associated factors and the prevalence of anxiety and depression in this special group in China. METHODS: Data from 511 patients with ED aged 18-60 years were collected between July 2021 and April 2022. The 5-item International Index of Erectile Function (IIEF-5) questionnaire, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate erectile function, anxiety and depression, respectively. Univariate analysis and multivariate linear regression analyses were used to explore the associated factors of depression and anxiety. RESULTS: The prevalence of anxiety and depression among ED patients was 38.16% and 64.97%, respectively. The mean anxiety index score was 47.37 ± 6.69 points, and the mean depression index was 54.72 ± 9.10 points. Multiple linear regression analysis showed that worse ED, low education level, and smoking were positively associated with increased risk of anxiety and depression. In addition, younger age, longer onset time, and irregular sleep were positively associated with high risk of anxiety, and irregular exercise was associated with severe depression. CONCLUSIONS: The prevalence of depression and anxiety in ED patients is high, and the severity of ED, age, education level, smoking, onset time, regular sleep, and exercise were associated with anxiety or depression. Reversible risk factors should be avoided and individualized psychological support services are necessary for ED patients.

Cuproptosis-related lncRNA signatures predict prognosis and immune relevance of kidney renal papillary cell carcinoma.

Kidney renal papillary cell carcinoma (KIRP) has a high mortality rate and a poor prognosis. Cu concentrations differed significantly between renal cancer tissues and adjacent normal tissues. Cuproptosis is a newly identified cell death. Long non-coding RNAs (lncRNAs) play a crucial role in the progression of KIRP. In this study, we focused on constructing and validating cuproptosis-related lncRNA signatures to predict the prognosis of KIRP patients and their immune correlation. We created prognosis models using Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. We found that patients in the high-risk group had poorer overall survival (OS) and progression-free survival (PFS) and higher mortality. Risk score and stage are prognosis factors independent of other clinical features. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and C-index curves showed that cuproptosis-related lncRNA signatures could more accurately predict the prognosis of patients. Functional enrichment analysis suggests that the function of differentially expressed genes (DEGs) is associated with KIRP development and immunity. In immune-related function analysis, we found a significant difference in parainflammation responses between high-risk and low-risk groups. The mutation frequencies of TTN, MET, KMT2C, PKHD1, SETD2, and KMT2D genes in the high-risk group were higher than those in the low-risk group, but the mutation frequencies of MUC16, KIAA109, CUBN, USH2A, DNAH8 and HERC2 genes were significantly lower than those in the low-risk group. Survival analysis of tumor mutation burden (TMB) and combined TMB-risk showed better OS in patients with high TMB. Immune infiltration and immune checkpoint analysis assessed the immune association of six high mutation frequency genes (TTN, MET, KMT2C, PKHD1, SETD2, and KMT2D) with KIRP. Finally, we performed a drug sensitivity analysis and screened 15 potential drugs that differed between high-risk and low-risk patients. In this study, we constructed and validated cuproptosis-related lncRNA signatures that can more accurately predict the prognosis of KIRP patients and provide new potential therapeutic targets and prognosis markers for KIRP patients.