DEAD-Box Helicase 17 exacerbates non-alcoholic steatohepatitis via transcriptional repression of cyp2c29, inducing hepatic lipid metabolism disorder and eliciting the activation of M1 macrophages.

OBJECTIVE: Our study was to elucidate the role of RNA helicase DEAD-Box Helicase 17 (DDX17) in NAFLD and to explore its underlying mechanisms. METHODS: We created hepatocyte-specific Ddx17-deficient mice aim to investigate the impact of Ddx17 on NAFLD induced by a high-fat diet (HFD) as well as methionine and choline-deficient l-amino acid diet (MCD) in adult male mice. RNA-seq and lipidomic analyses were conducted to depict the metabolic landscape, and CUT&Tag combined with chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted. RESULTS: In this work, we observed a notable increase in DDX17 expression in the livers of patients with NASH and in murine models of NASH induced by HFD or MCD. After introducing lentiviruses into hepatocyte L02 for DDX17 knockdown or overexpression, we found that lipid accumulation induced by palmitic acid/oleic acid (PAOA) in L02 cells was noticeably weakened by DDX17 knockdown but augmented by DDX17 overexpression. Furthermore, hepatocyte-specific DDX17 knockout significantly alleviated hepatic steatosis, inflammatory response and fibrosis in mice after the administration of MCD and HFD. Mechanistically, our analysis of RNA-seq and CUT&Tag results combined with ChIP and luciferase reporter assays indicated that DDX17 transcriptionally represses Cyp2c29 gene expression by cooperating with CCCTC binding factor (CTCF) and DEAD-Box Helicase 5 (DDX5). Using absolute quantitative lipidomics analysis, we identified a hepatocyte-specific DDX17 deficiency that decreased lipid accumulation and altered lipid composition in the livers of mice after MCD administration. Based on the RNA-seq analysis, our findings suggest that DDX17 could potentially have an impact on the modulation of lipid metabolism and the activation of M1 macrophages in murine NASH models. CONCLUSION: These results imply that DDX17 is involved in NASH development by promoting lipid accumulation in hepatocytes, inducing the activation of M1 macrophages, subsequent inflammatory responses and fibrosis through the transcriptional repression of Cyp2c29 in mice. Therefore, DDX17 holds promise as a potential drug target for the treatment of NASH.

Acute psychological impact on COVID-19 patients in Hubei: a multicenter observational study.

We conducted a multicentre cross-sectional survey of COVID-19 patients to evaluate the acute psychological impact on the patients with coronavirus disease 2019 (COVID-19) during isolation treatment based on online questionnaires from 2 February to 5 March 2020. A total of 460 COVID-19 patients from 13 medical centers in Hubei province were investigated for their mental health status using online questionnaires (including Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Patient Health Questionnaire-15, and Insomnia Severity Index scales). Among all 460 COVID-19 patients, 187 (40.65%) of them were healthcare workers (HCWs). 297 (64.57%) of them were females. The most common psychological problems were somatization symptoms (66.09%, n = 304), followed by depression (53.48%, n = 246), anxiety (46.30%, n = 213), problems of insomnia (42.01%, n = 171), and then self-mutilating or suicidal thoughts (23.26%, n = 107). Of all the patients, 15.65% (n = 72) had severe somatization symptoms, and 2.83% (n = 13) had severe (almost every day) self-mutilating or suicidal thoughts. The most common psychological problems for HCWs were somatization symptoms (67.84%, n = 125), followed by depression (51.87%, n = 97), anxiety (44.92%, n = 84), problems of insomnia (36.18%, n = 55), and then self-mutilating or suicidal thoughts (20.86%, n = 39). Patients with lower education levels were found to be associated with higher incidence of self-mutilating or suicidal thoughts (odds ratio [OR], 2.68, 95% confidence interval [95% CI], 1.66-4.33 [P < 0.001]). Patients with abnormal body temperature were found to be associated with higher incidence of self-mutilating or suicidal thoughts (OR, 3.97, 95% CI, 2.07-7.63 [P < 0.001]), somatic symptoms (OR, 2.06, 95% CI, 1.20-3.55 [P = 0.009]) and insomnia (OR, 1.66, 95% CI, 1.04-2.65 [P = 0.033]). Those with suspected infected family members displayed a higher prevalence of anxiety than those without infected family members (OR, 1.61, 95% CI, 1.1-2.37 [P = 0.015]). Patients at the age of 18-44 years old had fewer somatic symptoms than those aged over 45 years old (OR, 1.91, 95% CI, 1.3-2.81 [P = 0.001]). In conclusion, COVID-19 patients tended to have a high prevalence of adverse psychological events. Early identification and intervention should be conducted to avoid extreme events such as self-mutilating or suicidal impulsivity for COVID-19 patients, especially for those with low education levels and females who have undergone divorce or bereavement.

Prevalence of psychological disorders in the COVID-19 epidemic in China: A real world cross-sectional study.

OBJECTIVE: This study aimed to explore the prevalence of psychological disorders and associated factors at different stages of the COVID-19 epidemic in China. METHODS: The mental health status of respondents was assessed via the Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI) and the Generalized Anxiety Disorder 7 (GAD-7) scale. RESULTS: 5657 individuals participated in this study. History of chronic disease was a common risk factor for severe present depression (OR 2.2, 95% confidence interval [CI], 1.82-2.66, p < 0.001), anxiety (OR 2.41, 95% CI, 1.97-2.95, p < 0.001), and insomnia (OR 2.33, 95% CI, 1.83-2.95, p < 0.001) in the survey population. Female respondents had a higher risk of depression (OR 1.61, 95% CI, 1.39-1.87, p < 0.001) and anxiety (OR 1.35, 95% CI, 1.15-1.57, p < 0.001) than males. Among the medical workers, confirmed or suspected positive COVID-19 infection as associated with higher scores for depression (confirmed, OR 1.87; suspected, OR 4.13), anxiety (confirmed, OR 3.05; suspected, OR 3.07), and insomnia (confirmed, OR 3.46; suspected, OR 4.71). LIMITATION: The cross-sectional design of present study presents inference about causality. The present psychological assessment was based on an online survey and on self-report tools, albeit using established instruments. We cannot estimate the participation rate, since we cannot know how many potential subjects received and opened the link for the survey. CONCLUSIONS: Females, non-medical workers and those with a history of chronic diseases have had higher risks for depression, insomnia, and anxiety. Positive COVID-19 infection status was associated with higher risk of depression, insomnia, and anxiety in medical workers.