RNA-binding protein hnRNPR reduces neuronal cholesterol levels by binding to and suppressing HMGCR.

Recent studies have identified multiple RNA-binding proteins tightly associated with lipid and neuronal cholesterol metabolism and cardiovascular disorders. However, the role of heterogeneous nuclear ribonucleoprotein R (hnRNPR) in cholesterol metabolism and homeostasis, whether it has a role in regulating 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), is largely unknown. This research identifies hnRNPR as a repressor of HMGCR. Knockdown and overexpression of hnRNPR in cultured neuroblastoma cell (N2a) and MN1 cell lines enhances and inhibits HMGCR in vitro, respectively. hnRNPR may exert its repressive activity on HMGCR mRNA and protein levels by using its RNA recognition motif (RRM) in recognizing and modulating the stability of HMGCR transcript. Our RNA immunoprecipitation and luciferase reporter assays demonstrate a direct interaction between hnRNPR and HMGCR mRNA. We also demonstrated that hnRNR binds to the 3' untranslated region (3' UTR) of HMGCR and reduces its translation, while hnRNPR silencing increases HMGCR expression and cholesterol levels in MN1 and N2a cells. Overexpression of HMGCR significantly restores the decreased cholesterol levels in hnRNPR administered cells. Taken together, we identify hnRNPR as a novel post-transcriptional regulator of HMGCR expression in neuronal cholesterol homeostasis.

Prevalence of COVID-19 Diagnostic Output with Chest Computed Tomography: A Systematic Review and Meta-Analysis.

BACKGROUND: The pooled prevalence of chest computed tomography (CT) abnormalities and other detailed analysis related to patients' biodata like gender and different age groups have not been previously described for patients with coronavirus disease 2019 (COVID-19), thus necessitating this study. Objectives: To perform a meta-analysis to evaluate the diagnostic performance of chest CT, common CT morphological abnormalities, disease prevalence, biodata information, and gender prevalence of patients. METHODS: Studies were identified by searching PubMed and Science Direct libraries from 1 January 2020 to 30 April 2020. Pooled CT positive rate of COVID-19 and RT-PCR, CT-imaging features, history of exposure, and biodata information were estimated using the quality effect (QE) model. RESULTS: Out of 36 studies included, the sensitivity was 89% (95% CI: 80-96%) and 98% (95% CI: 90-100%) for chest CT and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The pooled prevalence across lesion distribution were 72% (95% CI: 62-80%), 92% (95% CI: 84-97%) for lung lobe, 88% (95% CI: 81-93%) for patients with history of exposure, and 91% (95% CI: 85-96%) for patients with all categories of symptoms. Seventy-six percent (95% CI: 67-83%) had age distribution across four age groups, while the pooled prevalence was higher in the male with 54% (95% CI: 50-57%) and 46% (95% CI: 43-50%) in the female. CONCLUSIONS: The sensitivity of RT-PCR was higher than chest CT, and disease prevalence appears relatively higher in the elderly and males than children and females, respectively.

Toxicological evaluation of the aqueous stem bark extract of Bridelia ferruginea (Euphorbiaceae) in rodents.

Bridelia ferruginea is a woody shrub that grows in the Savannah or rain forests of Africa and has traditionally been used to treat diabetes, arthritis and boils. Despite all these uses, extensive toxicological evaluation has not been carried out. The aim of the present investigation was to evaluate the sub-chronic toxicological effects of the stem bark aqueous extract of Bridelia ferruginea in rats. The lethal dose (LD50) was determined using probit analysis and graded doses of the extract (250-4000 mg/kg) were administered to the animals via oral and intraperitoneal routes and observed for mortality, behavioral changes and signs of toxicity. Sub-chronic toxicity study was carried out at doses of 1 000, 2 000 and 4 000 mg/kg administered daily for 60 days. The animals were sacrificed after 60 days. Blood was collected for biochemical (renal and hepatic), hematological, oxidative stress, sperm and histopathological examinations, using standard methods. LD50 of the extract was estimated as >4 000 mg/kg orally; neither significant visible signs of toxicity nor mortality were observed. There were no significant differences in the animals and organ weights, hematological and biochemical parameters in the treated groups compared to the control group. However, a significant increase (p<0.05) in the level of lipid peroxidation and a significant (p<0.05) decrease in sperm count were observed in the treated animals compared with the control group. The stem-bark aqueous extract of Bridelia ferruginea was found to be relatively safe, though it has the potential to cause lipid peroxidation and damage sperm quality and should thus be used with caution.