Impact of internet plus health education on urinary stoma caregivers in coping with care burden and stress in the era of COVID-19.

Objective: To explore the impact of "Internet Plus Health Education" on coping with care burden and pressure in urinary stoma caregivers in the era of COVID-19. Materials and methods: Eighty caregivers of patients with urinary ostomy were equally randomized to experimental and control groups. Caregivers in the experimental group received digital nursing education intervention, which involved nursing intervention of Internet Plus Health Education (IPHE), and those in the control group received conventional care instructions. Six months later, care burden and emotional pressure were assessed in all caregivers using the Zarit Caregiver Burden Interview (ZBI) and the Simplified Coping Style Questionnaire (SCSQ). Results: Before the intervention, the ZBI and SCSQ scores were comparable between both groups (p > 0.05). After the intervention, the ZBI scores in the experimental group were significantly higher than in the control group and vice versa for SCSQ scores (p < 0.01). Furthermore, after the intervention, the family care satisfaction scale (FCSS) of the experimental group was significantly higher than the control group. Conclusion: Providing "Internet Plus Health Education" to urinary stoma caregivers can reduce their care burden and enhance their pressure-coping ability in the COVID-19 era.

Interference with lncRNA NEAT1 promotes the proliferation, migration, and invasion of trophoblasts by upregulating miR-411-5p and inhibiting PTEN expression.

Background: Preeclampsia (PE) is an idiopathic hypertensive disorder of pregnancy, which is related to abnormal placental villi development. Our previous study has found that lncRNA NEAT1 promotes apoptosis of trophoblasts, but the role of NEAT1 in proliferation, migration, and invasion is still unclear. This study explores the role of NEAT1 in proliferation, migration, and invasion of trophoblasts.Methods: NEAT1 and miR-411-5p levels were detected by quantitative real-time PCR. Colony formation assay detected cell proliferation and transwell assay detected cell migration and invasion. Dual-luciferase reporter assay detected the binding between NEAT1 and miR-411-5p as well as the binding between miR-411-5p and PTEN. RNA pull-down assay detected the combination between NEAT1 and miR-411-5p.Result: NEAT1 was increased and miR-411-5p was reduced in PE patients and human trophoblasts (HTR8/SVneo cells) that were induced with H2O2. Interference with NEAT1 promoted cell proliferation, migration, and invasion, and the miR-411-5p inhibitor reversed the effect of siRNA-NEAT1. The expression of PTEN was promoted in PE patients and HTR8/SVneo cells that were induced with H2O2, while the miR-411-5p mimic inhibited PTEN expression, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic. Besides, under H2O2 induction, the miR-411-5p mimic promoted cell proliferation, migration, and invasion, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic.Conclusion: Interference with lncRNA NEAT1 promoted the proliferation, migration, and invasion of trophoblasts and alleviated the development of PE, which was partly mediated by upregulating miR-411-5p and inhibiting PTEN expression.

Epigenetically-Regulated MicroRNA-9-5p Suppresses the Activation of Hepatic Stellate Cells via TGFBR1 and TGFBR2.

BACKGROUND/AIMS: Recently, microRNAs (miRNAs) have been demonstrated to act as regulators of activation of hepatic stellate cells (HSCs). It is well known that the main profibrogenic inducer transforming growth factor-ß1 (TGF-ß1) contributes to HSC activation, which is a key event in liver fibrosis. Increasing studies show that miR-9-5p is down-regulated in liver fibrosis and restoration of miR-9-5p limits HSC activation. However, the role of miR-9-5p in TGF-ß1-induced HSC activation is still not clear. METHODS: miR-9-5p expression was quantified using real-time PCR in chronic hepatitis B (CHB) patients and TGF-ß1-treated LX-2 cells. In CHB patients, histological activity index (HAI) and fibrosis stages were assessed using the Ishak scoring system. Effects of miR-9-5p on liver fibrosis in vivo and in vitro were analyzed. Luciferase activity assays were performed to examine the binding of miR-9-5p to the 3'-untranslated region of type I TGF-ß receptor (TGFBR1) as well as TGFBR2. RESULTS: Compared with healthy controls, miR-9-5p was reduced in CHB patients. There was a lower miR-9-5p expression in CHB patients with higher fibrosis scores or HAI scores. miR-9-5p was down-regulated by TGF-ß1 in a dose-dependent manner. TGF-ß1-induced HSC activation including cell proliferation, α-SMA and collagen expression was blocked down by miR-9-5p. Notably, miR-9-5p ameliorates carbon tetrachloride-induced liver fibrosis. As determined by luciferase activity assays, TGFBR1 and TGFBR2 were targets of miR-9-5p. Further studies demonstrated that miR-9-5p inhibited TGF-ß1/Smads pathway via TGFBR1 and TGFBR2. Interestingly, promoter methylation was responsible for miR-9-5p down-regulation in liver fibrosis. The relationship between miR-9-5p expression and methylation was confirmed in CHB patients and TGF-ß1-treated cells. CONCLUSION: Our results demonstrate that miR-9-5p could inhibit TGF-ß1-induced HSC activation through TGFBR1 and TGFBR2. Loss of miR-9-5p is associated with its methylation status in liver fibrosis.

Serum lincRNA-p21 as a potential biomarker of liver fibrosis in chronic hepatitis B patients.

Serum long non-coding RNAs (lncRNAs) are emerging as promising biomarkers for various human diseases. The aim of this study was to investigate the feasibility of using serum long intergenic non-coding RNA-p21 (lincRNA-p21) as a biomarker for chronic hepatitis B patients. Serum lincRNA-p21 levels were quantified using real-time PCR in 417 CHB patients and 363 healthy controls. The promoter methylation level of lincRNA-p21 was detected using bisulphite-sequencing analysis in primary hepatic stellate cells (HSCs). Sera from hepatitis B-infected patients contained lower levels of lincRNA-p21 than sera from healthy controls. Serum lincRNA-p21 levels negatively correlated with stages of liver fibrosis in infected patients. Receiver operating characteristic (ROC) curve analyses suggested that serum lincRNA-p21 had a significant diagnostic value for liver fibrosis in these patients. It yielded an area under the curve of ROC of 0.854 with 100% sensitivity and 70% specificity in discriminating liver fibrosis from healthy controls. There was additionally a negative correlation between serum lincRNA-p21 level and the markers of liver fibrosis including α-SMA and Col1A1. However, there was no correlation of serum lincRNA-p21 level with the markers of viral replication, liver inflammatory activity, and liver function. Notably, during primary HSCs culture, loss of lincRNA-p21 expression was associated with promoter methylation. Serum lincRNA-p21 could serve as a potential biomarker of liver fibrosis in CHB patients. Down-regulation of lincRNA-p21 in liver fibrosis may be associated with promoter methylation.

Activation of Hepatic Stellate Cells is Inhibited by microRNA-378a-3p via Wnt10a.

BACKGROUND/AIMS: Wnt/ß-catenin pathway is involved in liver fibrosis and microRNAs (miRNAs) are considered as key regulators of the activation of hepatic stellate cells (HSCs). A recent study showed the protective role of miR-378a-3p against cardiac fibrosis. However, whether miR-378a-3p suppresses Wnt/ß-catenin pathway in liver fibrosis is largely unknown. METHODS: miR-378a-3p expression was detected in carbon tetrachloride-induced liver fibrosis and activated HSCs. Effects of miR-378a-3p overexpression on HSC activation and Wnt/ß-catenin pathway were analyzed. Bioinformatic analysis was employed to identify the potential targets of miR-378a-3p. Serum miR-378a-3p expression was analyzed in patients with cirrhosis. RESULTS: Reduced miR-378a-3p expression was observed in the fibrotic liver tissues and activated HSCs. Up-regulation of miR-378a-3p inhibited HSC activation including cell proliferation, α-smooth muscle actin (α-SMA) and collagen expression. Moreover, miR-378a-3p overexpression resulted in Wnt/ß-catenin pathway inactivation. Luciferase reporter assays demonstrated that Wnt10a, a member of Wnt/ß-catenin pathway, was confirmed to be a target of miR-378a-3p. By contrast, miR-378a-3p inhibitor contributed to HSC activation, with an increase in cell proliferation, α-SMA and collagen expression. But all these effects were blocked down by silencing of Wnt10a. Notably, sera from patients with cirrhosis contained lower levels of miR-378a-3p than sera from healthy controls. Receiver operating characteristic curve analysis suggested that serum miR-378a-3p differentiated liver cirrhosis patients from healthy controls, with an area under the curve of ROC curve of 0.916. CONCLUSION: miR-378a-3p suppresses HSC activation, at least in part, via targeting of Wnt10a, supporting its potential utility as a novel therapeutic target for liver fibrosis.

Inhibition of ATIR by shRNA prevents collagen synthesis in hepatic stellate cells.

Currently, strategies aimed at disrupting renin-angiotensin-aldosterone system (RAAS) are extensively investigated for treating liver fibrosis. However, the experiment results remain unsatisfactory, mainly due to excessive level of angiotensin II (AngII) in gene expression. In this article, we aim to investigate whether suppression of AngII-type I receptor (ATIR) expression by short hairpin RNA (shRNA) expression vectors decreases the level of collagen synthesis in hepatic stellate cells (HSCs). Three pairs of ATIR-targeted shRNA expression vectors were transfected into HSC-T6 cells. Compared with the control group, both mRNA and protein levels of ATIR expression were significiently decreased in shRNA-treated groups, and the inhibitory effect exhibited a dose- and time-dependent pattern. Accordingly, TGF-ß1 mRNA expression in shRNA1 group was reduced by about 54% compared with the control group. The level of Procollagen type III, hyaluronic acid, and laminin declined by about 46.4, 52.6, and 42%, respectively. In conclusion, shRNA expression vectors targeting ATIR could attenuate collagen synthesis.