Abstract:The coronavirus disease 2019 (COVID-19) pandemic is a major public health event caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread widely all over the world. A high proportion of patients become severely or critically ill, and suffer high mortality due to respiratory failure and multiple organ dysfunction. Therefore, providing timely and effective treatment for critically ill patients is essential to reduce overall mortality. Convalescent plasma therapy and pharmacological treatments, such as aerosol inhalation of interferon-α (IFN-α), corticosteroids, and tocilizumab, have all been applied in clinical practice; however, their effects remain controversial. Recent studies have shown that extracorporeal therapies might have a potential role in treating critically ill COVID-19 patients. In this review, we examine the application of continuous renal replacement therapy (CRRT), therapeutic plasma exchange (TPE), hemoadsorption (HA), extracorporeal membrane oxygenation (ECMO), and extracorporeal carbon dioxide removal (ECCO2R) in critically ill COVID-19 patients to provide support for the further diagnosis and treatment of COVID-19.
Abstract:This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure (HF)-related stroke. HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and hub genes. Gene Ontology (GO) and pathway enrichment analyses were performed on genes in the key modules. Genes in HF- and stroke-related key modules were intersected to obtain common genes for HF-related stroke, which were further intersected with hub genes of stroke-related key modules to obtain key genes in HF-related stroke. Key genes were functionally annotated through GO in the Reactome and Cytoscape databases. Finally, key genes were validated in these two datasets and other datasets. HF- and stroke-related datasets each identified two key modules. Functional enrichment analysis indicated that protein ubiquitination, Wnt signaling, and exosomes were involved in both HF- and stroke-related key modules. Additionally, ten hub genes were identified in stroke-related key modules and 155 genes were identified as common genes in HF-related stroke. OTU deubiquitinase with linear linkage specificity(OTULIN) and nuclear factor interleukin 3-regulated(NFIL3) were determined to be the key genes in HF-related stroke. Through functional annotation, OTULIN was involved in protein ubiquitination and Wnt signaling, and NFIL3 was involved in DNA binding and transcription. Importantly, OTULIN and NFIL3 were also validated to be differentially expressed in all HF and stroke groups. Protein ubiquitination, Wnt signaling, and exosomes were involved in HF-related stroke. OTULIN and NFIL3 may play a key role in HF-related stroke through regulating these processes, and thus serve as promising intervention targets.
Abstract:Abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry (LC-MS). A total of 18 remarkably different metabolites were identified, and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS, with an area under the curve (AUC) of 0.93. Subsequently, we analyzed both the metabolomics and transcriptomics data and found that seven metabolites, especially 2'-deoxy-D-ribose (2dDR), were significantly correlated with differentially expressed genes. In conclusion, our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients, and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.
Abstract:Clinically, a large proportion of glaucoma patients undergo repeated intraocular pressure (IOP) spike (Spike IOP) attacks during their sleep, which may facilitate retinopathy. In this study, we established a mouse model of repeated transient Spike IOP to investigate the direct damage to the retina following Spike IOP attacks, and elucidated the underlying molecular mechanism. We analyzed the changes in the number of retinal ganglion cells (RGCs) via immunofluorescence. Thereafter, we detected retinal cell apoptosis via terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining, and performed RNA sequencing (RNA-seq) to reveal the underlying molecular mechanism. Finally, we validated the expression of key molecules in the endoplasmic reticulum (ER) stress pathway using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Results revealed a time-dependent RGC loss in Spike IOP, evidenced by a reduction in the number of Brn3a-positive RGCs in experimental eyes following a 7-d continuous treatment with Spike IOP. In addition, TUNEL staining indicated that apoptosis of retinal cells started in the outer nuclear layer (ONL), and then spread to the ganglion cell layer (GCL) with time. RNA-seq analysis revealed that ER stress might be involved in Spike IOP-induced retinal injury. This result was corroborated by western blot, which revealed upregulation of ER stress-related proteins including binding immunoglobulin protein/glucose-regulated protein 78 (BiP/GRP78), phosphorylated inositol-requiring enzyme 1 (p-IRE1), unspliced X-box-binding protein 1 (XBP1-u), spliced X-box-binding protein 1 (XBP1-s), phosphorylated c-Jun N-terminal kinase (p-JNK), C/EBP-homologous protein (CHOP), and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax). These findings indicate that repeated IOP transients are detrimental to the retina, while ER stress plays an important role in retinal cell apoptosis in this situation. Notably, repeated Spike IOP among glaucoma patients is a crucial factor for progressive retinopathy.
Abstract:Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2, also called IMP2) plays an essential role in the development and maturation of germ cells and embryos and is a candidate gene for goat litter size, based on a previous genome-wide selective sweep analysis. In this study, the mRNA expression level of IGF2BP2 was found to be significantly higher in a single-lamb group than in a multi-lamb group. Insertions/deletions (indels) within the goat IGF2BP2 gene, including P4-Ins-13bp and P5-Del-12bp, were verified in 918 Shaanbei White Cashmere (SBWC) female goats. The minor allelic frequencies (MAFs) of P4-Ins-13bp and P5-Del-12bp loci were 0.349 and 0.295, respectively. Analysis using the Chi-square (χ2) test showed that the genotype (χ2=14.479, P=0.006) distribution of P4-Ins-13bp was significantly different between the single-lamb and multi-lamb groups. Correlation analysis demonstrated that P4-Ins-13bp was significantly associated with goat litter size (P=0.022), and individual goats with the homozygous deletion/deletion (DD) genotype produced more litters than other goats. Therefore, considered as a potential molecular marker significantly related to lambing traits, the P4-Ins-13bp mutation of the goat IGF2BP2 gene can be used in goat breeding with practical molecular marker-assisted selection (MAS) to optimize female reproduction and improve economic efficiency in the goat industry.