Background: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy. The aims of the present study were to screen the critical miRNA and corresponding target genes that related to development of ESCC by weighted gene correlation network analysis (WGCNA) and investigate the functions by experimental validation. Methods: Datasets of mRNA and miRNA expression data were downloaded from GEO. The R software was used for data preprocessing and differential expression gene analysis. The differentially expressed protein-coding genes (DEGs) and miRNAs (DEMs) were selected (FDR 1.5). Meanwhile, 81 expression data of ESCC patients in TCGA combined with clinic information were applied by WGCNA to create networks. The correlational analyses between each module and clinical parameters were conducted, and enrichment analyses of GO and KEGG were subsequently performed. Then, a series of experiments were conducted in ESCC cells by use of miRNA mimics. Results: In total, 4,023 DEGs and 328 DEMs were screened. After checking good genes and samples, 3,841 genes (3,696 DEGs and 145 DEMs) were used for WGCNA. As a consequence, altogether 11 gene modules were found. Among them, the brown modules were found to be strongly inversely associated with pathological grade. Meanwhile, has-mir-92b, the only miRNA in brown module, had a positive correlation with grade and negatively correlated with potential target gene (KFL4 and DCS2) in the same module. Furthermore, an increased expression of miR-92b-3p and down-regulated KLF4 and DSC2 protein was detected in the ESCC clinical samples. Up-regulated miR-92b-3p shortened G0/G1 phase and promote ESCC cells invasion and migration. Furthermore, we verified that DSC2 and KFL4 was target genes of miR-92b-3p by luciferase report assay. Conclusion: WGCNA is an efficient approach to system biology. By this procedure, miR-92b-3p was identified as an ESCC-promoting gene by target KLF4 and DCS2.
7 September 2023 in International Immunopharmacology
Contrast‐induced nephropathy (CIN) is a condition that causes kidney damage in patients receiving angiography with iodine‐based contrast agents. This study investigated the potential protective effects of berberine (BBR) against CIN and its underlying mechanisms. The researchers conducted both in vivo and in vitro experiments to explore BBR's renal protective effects. In the in vivo experiments, SD rats were used to create a CIN model, and different groups were established. The results showed that CIN model group exhibited impaired renal function, severe damage to renal tubular cells and increased apoptosis and ferroptosis. However, BBR treatment group demonstrated improved renal function, decreased apoptosis and ferroptosis. Similar results were observed in the in vitro experiments using HK‐2 cells. BBR reduced ioversol‐induced apoptosis and ferroptosis, and exerted its protective effects through Akt/Foxo3a/Nrf2 signalling pathway. BBR administration increased the expression of Foxo3a and Nrf2 while decreasing the levels of p‐Akt and p‐Foxo3a. In conclusion, this study revealed that BBR effectively inhibited ioversol‐induced apoptosis and ferroptosis in vivo and in vitro. The protective effects of BBR were mediated through the modulation of Akt/Foxo3a/Nrf2 signalling pathway, leading to the alleviation of CIN. These findings suggest that BBR may have therapeutic potential for protecting against CIN in patients undergoing angiography with iodine‐based contrast agents.
The aim of this study is to investigate the impact of cognitive impairments on treatment compliance and quality of life in patients with Continuous Ambulatory Peritoneal Dialysis (CAPD). A cross-sectional study was conducted among patients with CAPD at the Department of Nephrology, Lianshui People’s Hospital from October 2021 to May 2022. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and the End-Stage Renal Disease Adherence Questionnaire was used to evaluate treatment compliance. Quality of life was assessed using the SF-36 questionnaire. Scores from all the questionnaires and demographic data were recorded. A total of 98 patients were enrolled, and the prevalence of cognitive impairment among CAPD patients was 69.39% (MoCA score < 26). Patients were divided into 2 groups: one group with normal cognitive function (MoCA score ≥ 26) and the other with cognitive impairments. There were statistically significant differences in age, dialysis age, education, urea clearance index, history of high blood pressure, and diabetes between the 2 groups (all P < .05). Patients with cognitive impairments had lower compliance levels in terms of diet fluid restriction, medication therapeutic regimens, and dialysis regimen (all P < .05). Patients with cognitive impairments also had lower quality of life scores in the dimensions of physical function, general health, social function, emotional function, and mental health (all P < .05). Cognitive impairment appears to be common among CAPD patients and may adversely affect both their treatment adherence and overall quality of life. A more comprehensive understanding of the underlying mechanisms necessitates further study.