Adult human mesenchymal stem cells have the potential to differentiate into osteoblast, which plays crucial roles in bone regeneration and repair. Some transcriptional factors (TFs), such as BMP-2 and RUNX2, have been demonstrated to control the differentiation processes. It is important to discover more key regulators in osteoblast differentiation. Recently, some studies found long noncoding RNAs (lncRNAs) participating in osteoblast differentiation, such as MALAT1, DANCR, and ANCR. In this study, we performed a network-based computational analysis to investigate the lncRNA-messenger RNA (mRNA) crosstalks via integrating microRNA (miRNA)-RNA interactions, gene coexpression, and protein-protein interactions.First, multiple topology analyses were performed to osteoblast-differentiationrelated lncRNA-mRNA network (ODLMN). Several lncRNAs with central topology structures were identified as key regulators. Results showed that these lncRNAs participated in osteoblast differentiation via phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase, and Ras signals. Previous studies have demonstrated that lncRNAs exert functions by involving in close modules. Second, after performing module searching in ODLMN, two functional modules were identified, which played crucial roles through involving in PI3K/protein kinase B, cyclic adenosine 3ʹ,5ʹ-monophosphate, and hypoxia-inducible factor 1 pathways. Third, a subset of core lncRNA-TF crosstalks that might form feedback loops to control the biological processes in osteoblast differentiation was identified. These core lncRNA-TF feedback loops showed more TF binding affinity than other lncRNAs.All these results can help us to uncover the molecular mechanism and provide new targets for bone regeneration and repair.
Background: The aim of this study was to find genes with significantly aberrant expression in diabetic nephropathy (DN) and determine their underlying mechanisms.Methods: GSE30528 and GSE1009 were obtained by querying the Gene Expression Omnibus (GEO) database. The difference in target gene expression between normal renal tissues and kidney tissues in patients with DN was screened by using the GEO2R tool. Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, differentially expressed genes (DEGs) were analysed by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then, the protein-protein interactions (PPIs) of DEGs were analyzed by Cytoscape with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes in this PPI network were recognized by centrality analysis.Results: There were 110 genes with significant expression differences between normal and DN tissues.The differences in gene expression involved many functions and expression pathways, such as the formation of the extracellular matrix and the construction of the extracellular domain. The correlation analysis and subgroup analysis of 14 hub genes and the clinical characteristics of DN showed that CTGF, ALB, PDPN,
Background: Colorectal cancer is among the most prominent malignant tumors endangering human health, with affected populations exhibiting an increasingly younger trend. The Kirsten ras (KRAS) gene acts as a crucial regulator in this disease and influences multiple signaling pathways. In the present study, the KRAS gene mutation-induced alteration of intestinal flora in colorectal cancer patients was explored, and the intestinal microbes that may be affected by the KRAS gene were examined to provide new insights into the diagnosis and treatment of colorectal cancer.Methods: Deoxyribonucleic acid (DNA) was extracted from 177 colorectal cancer patients in our hospital.The mutation of the KRAS gene was subsequently detected using real-time fluorescence quantitative polymerase chain reaction (qPCR), and survival analysis was performed. Moreover, genomic DNA was extracted from the fecal microbes in 30 of these patients, and the differences in the intestinal flora between mutation and non-mutation groups were evaluated using linear discriminant analysis (LDA) Effect size (LEfSe) analysis.Results: KRAS gene mutation substantially affected the distant metastasis of colorectal cancer, and the survival prognosis in the non-mutation group was significantly superior compared to the mutation group.The mutation group had a notably higher prevalence of microbes including Roseburia, Parabacteroides, Metascardovia, Staphylococcus, Staphylococcaceae, and Bacillales than the non-mutation group. The presence of microbes in the non-mutation group, such as Clostridiales, Bacteroidetes, Lachnospiraceae, Coprococcus, and Ruminococcaceae was markedly higher than in the mutation group. Firmicutes were negatively correlated with the presence of Actinomyces and Bacteroidetes, while Bacteroidetes were positively associated with the level of Actinomyces. Conclusions: In colorectal cancer, KRAS gene mutation can remarkably affect the survival prognosis and change the composition and abundance of intestinal flora, such as Roseburia, Parabacteroides, Metascardovia, Staphylococcus, and Bacillales, thereby influencing tumor development.
With the increasing incidence of end-stage renal disease (ESRD), patients’ life span and life quality are significantly reduced. Kidney transplantation has gradually become the ideal method for treating ESRD, and the shortage of organ sources has become the main problem. In recent years, China has successfully realized the transformation of organ sources. Voluntary donation after the death of citizens has increased year by year, and the number of kidney transplantations has increased, which alleviates the organ shortage to a certain extent, but compared with the past, the increasing proportion of aged donors has also become an inevitable global problem. At the same time, due to the sudden and widespread distribution of voluntary donation, most donor kidneys have the problem of longer cold ischemic time (CIT). The probability of adverse events, such as delayed renal function recovery after transplantation, was also significantly increased. At present, there is little research on the effect of donor’s aging and long CIT on the prognosis of renal transplantation. This paper reviews the literature in recent years and explore this problem from 2 aspects: the elderly donor and the long CIT.
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