Transcriptomics-based investigation of manganese dioxide nanoparticle toxicity in rats' choroid plexus.

Manganese dioxide nanoparticles (MnO2-NPs) have a wide range of applications in biomedicine. Given this widespread usage, it is worth noting that MnO2-NPs are definitely toxic, especially to the brain. However, the damage caused by MnO2-NPs to the choroid plexus (CP) and to the brain after crossing CP epithelial cells has not been elucidated. Therefore, this study aims to investigate these effects and elucidate potential underlying mechanisms through transcriptomics analysis. To achieve this objective, eighteen SD rats were randomly divided into three groups: the control group (control), low-dose exposure group (low-dose) and high-dose exposure group (high-dose). Animals in the two treated groups were administered with two concentrations of MnO2-NPs (200 mg kg-1 BW and 400 mg kg-1 BW) using a noninvasive intratracheal injection method once a week for three months. Finally, the neural behavior of all the animals was tested using a hot plate tester, open-field test and Y-type electric maze. The morphological characteristics of the CP and hippocampus were observed by H&E stain, and the transcriptome of CP tissues was analysed by transcriptome sequencing. The representative differentially expressed genes were quantified by qRT-PCR. We found that treatment with MnO2-NPs could induce learning capacity and memory faculty decline and destroy the structure of hippocampal and CP cells in rats. High doses of MnO2-NPs had a more obvious destructive capacity. For transcriptomic analysis, we found that there were significant differences in the numbers and types of differential genes in CP between the low- and high-dose groups compared to the control. Through GO terms and KEGG analysis, high-dose MnO2-NPs significantly affected the expression of transporters, ion channel proteins, and ribosomal proteins. There were 17 common differentially expressed genes. Most of them were transporter and binding genes on the cell membrane, and some of them had kinase activity. Three genes, Brinp, Synpr and Crmp1, were selected for qRT-PCR to confirm their expression differences among the three groups. In conclusion, high-dose MnO2-NPs exposure induced abnormal neurobehaviour, impaired memory function, destroyed the structure of the CP and changed its transcriptome in rats. The most significant DEGs in the CP were within the transport system.

CRP, SAA, LDH, and DD predict poor prognosis of coronavirus disease (COVID-19): a meta-analysis from 7739 patients.

Understanding factors associated with disease severity and mortality from coronavirus disease (COVID-19) was critical for effective risk stratification. We aimed to investigate the association between biomarkers of clinical laboratory tests, including serum C-reactive protein (CRP), serum amyloid protein (SAA), lactate dehydrogenase (LDH), and D-dimer (DD) and poor prognosis of COVID-19. We have searched many studies on COVID-19 on PubMed (Medline), Web of Science and Cochrane until 1 March 2021. The interest of this study was original articles reporting on laboratory testing projects and outcome of patients with COVID-19 that comprises mortality, acute respiratory distress syndrome (ARDS), need for care in an intensive care unit (ICU), and severe COVID-19. After synthesizing all data, we performed meta-analysis of random effects, and determined mean difference (MD) and standard mean difference at the biomarker level for different disease severity. A total of 7,739 patients with COVID-19 were pooled from 32 studies. CRP was significantly associated with poor prognosis of COVID-19 (SMD = 0.98, 95% CI = (0.85, 1.11), p < .001). Elevated SAA was associated with an increased composite poor outcome in COVID-19 (SMD = 1.06, 95% CI = (0.39, 1.72), p = .002). An elevated LDH was associated with a composite poor outcome (SMD = 1.18, 95% CI = (1.00, 1.36), p < .001). Patients with a composite poor outcome had a higher DD level (SMD = 0.91, 95% CI = (0.79, 1.02), p < .001). This meta-analysis showed that elevated serum CRP, SAA, LDH, and DD were associated with a poor outcome in COVID-19.