Death inducer obliterator (DIDO) is involved in apoptosis and embryonic stem cell self-renewal. Here, we investigate the effect of DIDO1 on bladder cancer cells and clarify the underlying molecular mechanism. Bladder cancer tissues and cell lines (T24, ScaBER, 5637), as well as normal bladder epithelial cells (SV-HUC-1), were used to measure the levels of DIDO1 mRNA and protein by qRT-PCR and western blot, respectively. The results indicated that DIDO1 was highly expressed in bladder cancer tissues and cell lines. And the expression of DIDO1 in T24 and 5637 cells was higher than that in ScaBER and SV-HUC-1 cells. The expression of DIDO1 was knocked down in T24 and 5637 cells by infection with shDIDO1-1 and shDIDO1-2 lentivirus. The growth of T24 and 5637 cells was monitored using Celigo, MTT assays, and colony formation assay. Apoptosis was examined by flow cytometric analysis. The effect of DIDO1 knockdown on tumorigenesis of T24 xenograft tumors was determined in nude mice. Reduction of DIDO1 mRNA resulted in reduced proliferation, decreased cell colony formation, increased apoptosis in vitro, and inhibited tumorigenesis in vivo. Furthermore, we identified signaling molecules involved in stress and apoptosis using the PathScan Antibody Array Kit and western blot. The depletion of DIDO1 significantly decreased the levels of phosphorylated SAPK/JNK, and Chk1/2, as well as the upregulating cleaved Caspase-7 expression. These results indicated that the potential mechanism of DIDO1 action might involve SAPK/JNK signaling cascades.
IntroductionDiamond‐Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome characterized by erythroid aplasia, physical malformation, and cancer predisposition. Twenty ribosomal protein genes and three non‐ribosomal protein genes have been identified associated with DBA.MethodsTo investigate the presence of novel mutations and gain a deeper understanding of the molecular mechanisms of disease, targeted next‐generation sequencing was performed in 12 patients with clinically suspected DBA. Literatures were retrieved with complete clinical information published in English by November 2022. The clinical features, treatment, and RPS10/RPS26 mutations were analyzed.ResultsAmong the 12 patients, 11 mutations were identified and 5 of them were novel (RPS19, p.W52S; RPS10, p.P106Qfs*11; RPS26, p.R28*; RPL5, p.R35*; RPL11, p.T44Lfs*40). Including 2 patients in this study, 13 patients with RPS10 mutations and 38 patients with RPS26 mutations were reported from 4 and 6 countries, respectively. The incidences of physical malformation in patients with RPS10 and RPS26 mutations (22% and 36%, respectively) were lower than the overall incidence in DBA patients (~50%). Patients with RPS26 mutations had a worse response rate of steroid therapy than RPS10 (47% vs. 87.5%), but preferred RBC transfusions (67% vs. 44%, p = 0.0253).ConclusionOur findings add to the DBA pathogenic variant database and demonstrate the clinical presentations of the DBA patients with RPS10/RPS26 mutations. It shows that next‐generation sequencing is a powerful tool for the diagnosis of genetic diseases such as DBA.
Objective: To observe the status quo of patients’ psychological distress, and to explore the effect of Internet+ health education model (IHEM) on patients who experienced psychological distress during their first hemodialysis treatment, with the goal of reducing their psychological distress and improving their quality of life. Methods: IHEM was conducted on 120 first-time hemodialysis patients for 3 months while a distress thermometer and a list of questionnaires were used to screen patients and provide corresponding psychological intervention. The incidence rate of psychological distress was analyzed statistically to explore the difference in psychological distress at various periods. Results: The incidence rate (score ≥ 4) of psychological distress in first-time hemodialysis patients was 46.67%, and their distress was mainly rooted in physical, emotional, practical problems (economy, time, and energy), etc. Through IHEM, the psychological distress scores of the patients decreased to 3.29 ± 1.02 at one month after their discharge, and the incidence rate was 32.14%; the psychological distress scores of the patients were 2.29 ± 1.02 at 3 months after their discharge, and the incidence rate was 21.14%. The difference before and after the intervention was statistically significant (P < 0.05). Conclusion: A psychological distress thermometer can timely detect the degree and causes of psychological distress among first-time hemodialysis patients, and the use of IHEM may significantly alleviate the psychological distress among hemodialysis patients.
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