Insight into the mechanism of DNA methylation and miRNA-mRNA regulatory network in ischemic stroke.

BACKGROUND: Epigenetic changes, such as DNA methylation and miRNA-target gene mechanisms, have recently emerged as key provokers in Ischemic stroke (IS) onset. However, cellular and molecular events harboring these epigenetic alterations are poorly understood. Therefore, the present study aimed to explore the potential biomarkers and therapeutic targets for IS. METHODS: miRNAs, mRNAs and DNA methylation datasets of IS were derived from the GEO database and normalized by PCA sample analysis. Differentially expressed genes (DEGs) were identified, and GO and KEGG enrichment analyses were performed. The overlapped genes were utilized to construct a protein-protein interaction network (PPI). Meanwhile, differentially expressed mRNAs and miRNAs interaction pairs were obtained from the miRDB, TargetScan, miRanda, miRMap and miTarBase databases. We constructed differential miRNA-target gene regulatory networks based on mRNA-miRNA interactions. RESULTS: A total of 27 up-regulated and 15 down-regulated differential miRNAs were identified. Dataset analysis identified 1053 and 132 up-regulated and 1294 and 9068 down-regulated differentially expressed genes in the GSE16561 and GSE140275 datasets, respectively. Moreover, 9301 hypermethylated and 3356 hypomethylated differentially methylated sites were also identified. Moreover, DEGs were enriched in terms related to translation, peptide biosynthesis, gene expression, autophagy, Th1 and Th2 cell differentiation, primary immunodeficiency, oxidative phosphorylation and T cell receptor signaling pathway. MRPS9, MRPL22, MRPL32 and RPS15 were identified as hub genes. Finally, a differential miRNA-target gene regulatory network was constructed. CONCLUSIONS: RPS15, along with hsa-miR-363-3p and hsa-miR-320e have been identified in the differential DNA methylation protein interaction network and miRNA-target gene regulatory network, respectively. These findings strongly posit the differentially expressed miRNAs as potential biomarkers to improve ischemic stroke diagnosis and prognosis.

Knowledge mapping of research on the mitochondrial unfolded protein response: a bibliometric and visual analysis.

Background: The mitochondrial unfolded protein response (UPRmt) is a mitochondria stress response, which exerts a crucial role in maintaining mitochondrial proteostasis during stress. However, there is no bibliometric analyses systematically studied this field which could comprehensively review research trends, evaluate publication performances and provide future perspectives. Methods: Articles investigating UPRmt published between 1994 and 2021 were downloaded from the Core Collection of the Web of Science (WOS). CiteSpace and VOSviewer bibliometric software were applied for bibliometric and visual analyses. Results: A total of 2,073 papers researching UPRmt were retrieved. According to the published number of papers, the field of UPRmt research has gone through its infancy (after 2000) and rapid growth (after 2021) phases. The United States and China contributed the most to UPRmt research. Regarding the distribution of institutions, Harvard University was the most influential institution. The most prolific authors are Johan Auwerx and CM Haynes. PLoS One is the most extensive journal in the field of UPRmt research, while the Cell Death and Differentiation journal had the greatest impact among the most-authored journals. Moreover, biochemistry/molecular biology, and cell biology are the largest subject areas. UPRmt research is mainly categorized as UPRmt, transcription, endoplasmic reticulum (ER) stress, lipotoxicity, mitophagy, inflammation, skeletal muscle, hypoxia, apoptosis, mitochondrial dysfunction, neurodegeneration, mitochondrial permeability transition, and integrated stress response. Conclusions: At present, research on UPRmt is booming. Further strengthening the cooperation and exchanges between countries, institutions, and authors in the future will surely promote the development of this field.

Mitochondrial unfolded protein response in ischemia-reperfusion injury.

Mitochondrial unfolded protein response (UPRmt) is a mitochondrial stress response that activates the transcriptional program of mitochondrial chaperone proteins and proteases to keep protein homeostasis in mitochondria. Ischemia-reperfusion injury results in multiple severe clinical issues linked to high morbidity and mortality in various disorders. The pathophysiology and pathogenesis of ischemia-reperfusion injury are complex and multifactorial. Emerging evidence showed the roles of UPRmt signaling in ischemia-reperfusion injury. Herein, we discuss the regulatory mechanisms underlying UPRmt signaling in C. elegans and mammals. Furthermore, we review the recent studies into the roles and mechanisms of UPRmt signaling in ischemia-reperfusion injury of the heart, brain, kidney, and liver. Further research of UPRmt signaling will potentially develop novel therapeutic strategies against ischemia-reperfusion injury.

The impact of insurance status on the survival outcomes of patients with renal cell carcinoma.

BACKGROUND: The impact of insurance status on renal cell carcinoma (RCC) patient survival is unclear. In this study, we investigated the effects of insurance status on the survival outcomes of RCC patients in the United States of America. METHODS: Data of patients diagnosed with RCC between 2007 and 2014 were obtained from the Surveillance, Epidemiology and End Results (SEER) database, a large national database including statistics on cancer patients. The Kaplan-Meier method and Cox regression analysis were used to determine the influence of insurance status on cancer-specific survival (CSS). RESULTS: A total of 30,951 eligible RCC patients were identified. Of these patients, 25,493 (82.37%) were insured, 3,959 (12.79%) had any Medicaid coverage, and 1,499 (4.84%) were uninsured. Kaplan-Meier analysis revealed that insurance status was associated with better CCS (P<0.001). The 5-year CSS rates of patients with insurance, any Medicaid, and no insurance were 88.3%, 82.6%, and 82.7%, respectively. Multivariate Cox regression analysis showed that patients with any Medicaid had poorer CSS than insured patients [hazard ratio (HR), 1.222; 95% confidence interval (CI), 1.100-1.357]. Stratified analysis revealed that at localized tumor stage and at regional tumor stage or among white patients, any Medicaid insurance was an independent predictor of an unfavorable survival outcome. CONCLUSIONS: Among the RCC patients in this study, individuals with insurance experienced improved CSS while individuals with any Medicaid tended to suffer worse survival outcomes.

The correlations between socioeconomic status and intrahepatic cholangiocarcinoma in the United States: a population-based study.

BACKGROUND: The incidence and mortality rates of intrahepatic cholangiocarcinoma (ICC) continue to increase in the United States (US). To our knowledge, the associations between socioeconomic factors (SES) and ICC-associated incidence and survival are still unclear. METHODS: We identified patients with ICC in the US Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2015. ICC incidence rates were calculated by directly age-adjusted to the 2000 US population. Univariate and multivariate Cox regression analyses were performed to find the influence of SES on ICC cause-specific survival (CSS) and overall survival (OS). Using disadvantageous SES, we generated a prognostic score model for risk stratification, then Kaplan-Meier analysis was performed to find the influence of SES on for ICC CSS/OS. RESULTS: A total of 3,456 ICC patients were included. Rates ratios (RR) for ICC incidence rates increased monotonically with ages and decreased with increasing county education levels. From three disadvantageous socioeconomic factors (i.e., unmarried status, uninsured status, median household income

Network and Pathway-Based Integrated Analysis Identified a Novel "rs28457673-miR-15/16/195/424/497 Family-IGF1R-MAPK Signaling Pathway" Axis Associated With Post-stroke Depression.

Single-nucleotide polymorphisms (SNPs) of microRNA (miRNA) (miRSNP) are SNPs located on miRNA genes or miRNA target sites, which have been supposed to be involved in the development of central nervous system diseases by interfering with miRNA-mediated regulatory functions. However, the association of miRSNP with post-stroke depression (PSD) has not been well-investigated. In this study, we collected 54 PSD risk genes via manual literature-mining and integrated PSD-related risk pathways based on multiple public databases. Furthermore, we systematically screened candidate functional miRSNPs for PSD and integrated a miRSNP-based PSD-associated pathway network, which included 99 miRNAs that target 12 PSD risk pathways. We also reviewed the association between three risk pathways and PSD pathogenetic mechanism thoroughly. Combining literature mining and network analysis, our results proposed an underlying mechanism of "miRSNP → miRNA → risk gene → pathway" axis effects on PSD pathogenesis, especially for rs28457673 (miR-15/16/195/424/497 family) → IGF1R → hsa04010 (MAPK signaling pathway). Our studies revealed a functional role in genetic modifier at the system level in the pathogenesis of PSD, which might provide further information for the miRSNP studies in PSD.

Marital status and survival in patients with renal cell carcinoma.

Previous studies have shown that marital status is an independent prognostic factor for survival in several types of cancer. In this study, we investigated the effects of marital status on survival outcomes among renal cell carcinoma (RCC) patients.We identified patients diagnosed with RCC between 1973 and 2013 from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier analysis and Cox regression were used to identify the effects of marital status on overall survival (OS) and cancer-specific survival (CSS).We enrolled 97,662 eligible RCC patients, including 64,884 married patients, and 32,778 unmarried (9831 divorced/separated, 9692 widowed, and 13,255 single) patients at diagnosis. The 5-year OS and CSS rates of the married, separated/divorced, widowed, and single patients were 73.7%, 69.5%, 58.3%, and 73.2% (OS), and 82.2%, 80.7%, 75.7%, and 83.3% (CSS), respectively. Multivariate Cox regression showed that, compared with married patients, widowed individuals showed poorer OS (hazard ratio, 1.419; 95% confidence interval, 1.370-1.469) and CSS (hazard ratio, 1.210; 95% confidence interval, 1.144-1.279). Stratified analyses and multivariate Cox regression showed that, in the insured and uninsured groups, married patients had better survival outcomes while widowed patients suffered worse OS outcomes; however, this trend was not significant for CSS.In RCC patients, married patients had better survival outcomes while widowed patients tended to suffer worse survival outcomes in terms of both OS and CSS.