Coronavirus disease 2019 (COVID‐19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been confirmed as of May 11, 2020. SARS‐CoV‐2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID‐19 severity and is also a crucial cause of death from COVID‐19. In the absence of antivirals and vaccines for COVID‐19, there is an urgent need to understand the cytokine storm in COVID‐19. Here, we have reviewed the current understanding of the features of SARS‐CoV‐2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID‐19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID‐19. This article is protected by copyright. All rights reserved.
Background End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). In addition to the structurally intact chromosome genomic DNA, there is a double-stranded circular DNA called extrachromosomal circular DNA (eccDNA), which is thought to be involved in the epigenetic regulation of human disease. However, the features of eccDNA in ESRD patients are barely known. In this study, we identified eccDNA from ESRD patients and healthy people, as well as revealed the characteristics of eccDNA in patients with ESRD. Methods Using the high-throughput Circle-Sequencing technique, we examined the eccDNA in peripheral blood mononuclear cells (PBMCs) from healthy people (NC) (n = 12) and ESRD patients (n = 16). We analyzed the length distribution, genome elements, and motifs feature of eccDNA in ESRD patients. Then, after identifying the specific eccDNA in ESRD patients, we explored the potential functions of the target genes of the specific eccDNA. Finally, we investigated the probable hub eccDNA using algorithms. Results In total, 14,431 and 11,324 eccDNAs were found in the ESRD and NC groups, respectively, with sizes ranging from 0.01 kb to 60 kb at most. Additionally, the ESRD group had a greater distribution of eccDNA on chromosomes 4, 11, 13, and 20. In two groups, we also discovered several motifs of specific eccDNAs. Furthermore, we identified 13,715 specific eccDNAs in the ESRD group and 10,585 specific eccDNAs in the NC group, both of which were largely annotated as mRNA catalog. Pathway studies using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that the specific eccDNA in ESRD was markedly enriched in cell junction and communication pathways. Furthermore, we identified potentially 20 hub eccDNA-targeting genes from all ESRD-specific eccDNA-targeting genes. Also, we found that 39 eccDNA-targeting genes were associated with ESRD, and some of these eccDNAs may be related to the pathogenesis of ESRD. Conclusions Our findings revealed the characteristics of eccDNA in ESRD patients and discovered potentially hub and ESRD-relevant eccDNA-targeting genes, suggesting a novel probable mechanism of ESRD.
Gestational diabetes mellitus (GDM) and preeclampsia (PE) are associated with maternal and infant health. Although the pathogenesis of PE and GDM remains controversial, oxidative stress is involved in the underlying pathology of GDM and PE. Protein lysine acetylation (Kac) plays an important regulatory role in biological processes. There is little data regarding the association of the maternal acetylome with GDM and PE. This study aimed to assess the potential value of the proteome and acetylome for GDM and PE. In our study, we included placental tissues from healthy individuals (n = 6), GDM patients (n = 6), and PE patients (n = 6) to perform 4D-label free quantification proteomics analysis and PRM analysis. We identified 22 significantly regulated proteins and 192 significantly regulated acetylated proteins between the GDM and PE groups. Furthermore, 192 significantly regulated acetylated proteins were mainly enriched in endoplasmic reticulum stress (ERS) and ferroptosis pathways. Seventeen acetylated sites in these two pathways were verified by PRM analysis. Our comprehensive analysis revealed key features of GDM/PE-significantly regulated acetylated proteins in the placentas from GDM and PE. The results of signaling pathway analysis focused on ERS and ferroptosis. These findings may help
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