Circ_0000029 Interacts with the miR-576-5p/KCNA1 Axis to Hamper the Development of Pediatric Asthma in an Asthma-Like in vitro Assessment.

OBJECTIVE: Numerous circular RNAs (circRNAs) have been verified to execute crucial roles in "asthma-like" progression of the airway smooth muscle cells (ASMCs). The present study aimed to scrutinize the function and mechanism of circ_0000029 in pediatric asthma etiology in vitro. METHODS: A cell model of asthma was developed using ASMCs induced by platelet-derived growth factor BB (PDGF-BB). Western blotting and qRT-PCR were performed to determine the expression levels of circ_0000029, miR-576-5p, and KCNA1 in PDGF-BB-treated ASMCs. Dual-luciferase reporter, RNA-binding protein immunoprecipitation, and RNA pull-down experiments were conducted to validate targeting relationships. CCK-8 and Transwell assays were performed to evaluate the proliferative and migratory potential of ASMCs. The rate of apoptosis was analyzed using flow cytometry. RESULTS: Pronounced circ_0000029 and KCNA1 downregulation and high levels of miR-576-5p were observed in PDGF-BB-treated ASMCs. Circ_0000029 targets miR-576-5p to regulate KCNA1 expression. The loss of KCNA1 and upregulation of miR-576-5p dramatically impeded apoptosis but promoted ASMC migration and proliferation. Ectopic expression of circ_0000029 manifested the opposite outcome among ASMCs. Furthermore, KCNA1 deficiency and miR-576-5p upregulation counteracted the effects of circ_0000029 overexpression on ASMCs. CONCLUSIONS: Circ_0000029 represses the abnormal migration and growth of ASMCs by mediating miR-576-5p and KCNA1 expression levels. This suggests that the regulatory axis circ_0000029/miR-576-5p/KCNA1 is a potential target for pediatric asthma treatment.

Serum magnesium in patients with severe acute respiratory syndrome coronavirus 2 from Wuhan, China.

The aim of the study was to evaluate the significance of hypomagnesemia in patients with coronavirus disease 2019 (COVID-19) and clarify its possible pathogenesis. A retrospective cohort study was conducted by reviewing 83 patients hospitalized in Guanggu district, Wuhan Third Hospital, China. Clinical histories, laboratory findings and outcome data were collected. Eighteen patients had hypomagnesemia during hospitalization. Fourteen patients were in the critical group and six died. In the critical group, serum magnesium (0.72 ± 0.15 mmol/L) was much lower than that in the moderate and severe groups. At the same time, we also found that several indicators are correlated with the level of magnesium. The level of magnesium was positively associated with the lymphocyte count (r = 0.203, P = 0.004) and platelet count (r = 0.217, P = 0.002) but negatively related to the levels of CRP (r = -0.277, P = 0.000), LDH (r = -0.185, P = 0.011) and α-hydroxybutyrate dehydrogenase (r = -0.198, P = 0.008) in the critical group. Hypomagnesemia might increase symptoms and may be associated with mortality in COVID-19 by affecting enzyme activity and activating the inflammatory response. Thus, magnesium might play a key role in the pathogenesis of COVID-19.

Case series of 20 pregnant women with 2019 novel coronavirus disease in Wuhan, China.

AIM: To evaluate perinatal outcomes regarding clinical presentation in pregnancy and the vertical transmission potential of COVID-19. METHODS: Clinical records, laboratory findings, and chest computed tomography (CT) scans were retrospectively reviewed from 20 pregnant patients with laboratory-confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University and The Third Hospital of Wuhan, from Jan 20 to Mar 16, 2020, including three in the first-trimester, two in the second-trimester, and 15 in the third-trimester. Evidence of vertical transmission was assessed by testing for neonatal throat swab samples. The pathological changes of COVID-19 on the placenta is evaluated by hematoxylin-eosin staining. RESULTS: The most common symptoms of the pregnant women with SARS-CoV-2 infection were fever and cough, which is comparable to the nonpregnant adults with COVID-19 infection. Nobody was transferred to intensive care unit (ICU) for treatment and there were no maternal and neonatal deaths. However, there was one case with induced abortions on first-trimester (due to pregnant woman's concerns about COVID-19), one diagnosed with ectopic pregnancy, no intrauterine fetal deaths during the study period. Delivery occurred in 15 patients in the third trimester. Their incidence of preterm birth was 20%. Three of the four preterm births were spontaneous. The average length of stay was 20.77 days. No neonatal SARS-CoV-2 infection was detected. There were two placentas found with acute chorioamnionitis, one showed normal placenta morphology. CONCLUSION: In this case series study, COVID-19 had no short-term adverse effect on pregnant women except premature birth. The vertical transmission of SARS-CoV-2 did not occur in our study.

iTRAQ-based high-throughput proteomics analysis reveals alterations of plasma proteins in patients infected with human bocavirus.

Human bocavirus (HBoV) is a member of the genus Bocavirus, family Parvoviridae, and subfamily Parvovirus and was first identified in nasopharyngeal aspirates of Swedish children with acute respiratory tract infection (ARTI) in 2005. It is the causative agent of nasopharyngeal aspirate disease and death in children. The HboV genomic structure is a linear single-stranded DNA (ssDNA). Its clinical pathogenic characteristics have been extensively studied, however, at present the molecular mechanism underlying the pathogenesis of HBoV infection is not completely clear. In this study, a total of 293 differentially expressed proteins (DEPs) between ARTI cases and healthy plasma samples were characterized using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled bioinformatics analysis, among which 148 were up-regulated and 135 were down-regulated. Gene Ontology (GO) and Cluster of Orthologous Groups of proteins (COG) annotated an enrichment of DEPs in complement activation and biological processes like immunity, inflammation, signal transduction, substance synthesis, and metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis enriched DEPs mainly in the Wnt signaling pathway (ko04310), PPAR signaling pathway (ko03320), intestinal immune network for IgA production (ko04672), complement and coagulation cascades (ko04610), Toll-like receptor signaling pathway (ko04620) and B cell receptor signaling pathway (ko04662). Further, expression levels of three candidate proteins (upregulated PPP2R1A and CUL1, and downregulated CETP) were validated using western blotting. Our investigation is the first analysis of the proteomic profile of HBoV-infected ARTI cases using the iTRAQ approach, providing a foundation for a better molecular understanding of the pathogenesis of ARTI in children.

Diagnostic Value Investigation and Bioinformatics Analysis of miR-31 in Patients with Lymph Node Metastasis of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.