Targeting cGAS-STING signaling protects retinal ganglion cells from DNA damage-induced cell loss and promotes visual recovery in glaucoma.

BACKGROUND: Glaucoma is an optic neurodegenerative disease. Retinal ganglion cells (RGCs) are the fundamental neurons in the trabecular meshwork, and their loss is the main pathological reason for glaucoma. The present study was to investigate mechanisms that regulate RGCs survival. METHODS: A mouse model of glaucoma was established by injecting hypertonic saline into the limbal veins. RGCs apoptosis was detected by using flow cytometry. Protein expressions in RGCs in response to DNA damage inducer cisplatin treatment were detected by immunofluorescence and western blot. The expressions of inflammatory cytokines were determined using ELISA and real-time PCR. RESULTS: In the hypertonic saline-injected mice, we found visual function was impaired followed by the increased expression of γH2AX and activation of cGAS-STING signaling. We found that DNA damage inducer cisplatin treatment incurred significant DNA damage, cell apoptosis, and inflammatory response. Mechanistically, cisplatin treatment triggered activation of the cGAS-STING signaling by disrupting mitochondrial function. Suppression of cGAS-STING ameliorated inflammation and protected visual function in glaucoma mice. CONCLUSIONS: The data demonstrated that cGAS-STING signaling is activated in the damaged retinal ganglion cells, which is associated with increased inflammatory responses, DNA damage, and mitochondrial dysfunction. Targeting the cGAS-STING signaling pathway represents a potential way to alleviate glaucoma-related visual function.

Functional roles of circular RNAs in lung injury.

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

Key genes involved with prognosis were identified in lung adenocarcinoma by integrated bioinformatics analysis.

Objective: By screening the core genes in lung adenocarcinoma (LUAD) with bioinformatics, our study evaluated its prognosis value and role in infiltration process of immune cells. Methods: Using GEO database, we screened 5 gene chips, including GSE11072, GSE32863, GSE43458, GSE115002, and GSE116959. Then, we obtained the corresponding differentially expressed genes by analyzed 5 gene chips online by GEO2R (P < 0.05, |logFC| > 1). Then, through DAVID online platform, Cytoscape 3.6.1 software and PPI network analysis, the network was visualized and obtain the final core genes. Next, we plan to use the GEPIA, UALCAN, Kaplan-Meier plotter and Time 2.0 database for corresponding analysis. The GEPIA database was used to verify the expression of core genes in LUAD and normal lung tissues, and survival analysis was used to evaluate the value of core genes in the prognosis of LUAD patients. UALCAN was used to verify the expression of the LUAD core gene and promoter methylation status, and the predictive value of core genes was evaluated in LUAD patients by the Kaplan-Meier plotter online tool. Then, we used the Time 2.0 database to identify the relationship to immune infiltration in LUAD. Finally, we used the human protein atlas (HPA) database for online immunohistochemical analysis of the expressed proteins. Results: The expression of CCNB2 and CDC20 in LUAD were higher than those in normal lung tissues, their increased expression was negatively correlated with the overall survival rate of LUAD, and they were involved in cell cycle signal transduction, oocyte meiosis signal transduction as well as the infiltration process of immune cells in LUAD. The expression proteins of CCNB2 and CDC20 were also different in lung cancer tissue and normal lung tissue. Therefore, CCNB2 and CDC20 were identified as the vital core genes. Conclusion: CCNB2 and CDC20 are essential genes that may constitute prognostic biomarkers in LUAD, they also participate the immune infiltration process and protein expression process of LUAD, and might provides basis for clinical anti-tumor drug research.

Circular RNA-mediated ceRNA network was identified in human lung adenocarcinoma by high-throughput sequencing.

OBJECTIVES: Aberrantly expressed circular RNAs (circRNAs) have been detected in many types of tumors. Hence, they are currently investigated as candidate biomarkers for diagnostic and potential targets for therapy in cancers. The objective of this study was to assess the expression profile of circRNA in lung adenocarcinoma (LUAD). METHODS: This study included 14 pairs of postoperative lung adenocarcinoma specimens, including cancer tissues and matched adjacent tissues. Second-generation sequencing was applied to the specimens to determine the circRNA expression in them among the 5242 distinct circRNAs detected. RESULTS: We identified a total of 18 significantly dysregulated circRNAs in the LUAD tissues: upregulation in four and downregulation in 14. ROC (The receiver operating characteristic curve) further suggested that hsa_circ_0120106, has_circ_0007342, has_circ_0005937, and circRNA_0000826 could potentially be used as biomarkers in the diagnosis of LUAD. Furthermore, study of the circRNA-microRNA (miRNA)-messenger RNA (mRNA) revealed interactions between the 18 dysregulated circRNA and several cancer-related miRNAs. Finally, a further Kyoto Encyclopedia of Genes and Genomes analysis showed that the cell cycle phase transition, p53 signaling pathway, AMP-activated protein kinase (AMPK) relative signaling pathway, and so on were key putative pathways in the process of LUAD. CONCLUSIONS: These findings demonstrated the correlation between abnormality in circRNA expression and LUAD, which lays the foundation of making CircRNAs candidate biomarkers in the diagnosis of LUAD.

Identification of Potential Key Genes and Prognostic Biomarkers of Lung Cancer Based on Bioinformatics.

Objective: To analyze and identify the core genes related to the expression and prognosis of lung cancer including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by bioinformatics technology, with the aim of providing a reference for clinical treatment. Methods: Five sets of gene chips, GSE7670, GSE151102, GSE33532, GSE43458, and GSE19804, were obtained from the Gene Expression Omnibus (GEO) database. After using GEO2R to analyze the differentially expressed genes (DEGs) between lung cancer and normal tissues online, the common DEGs of the five sets of chips were obtained using a Venn online tool and imported into the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein-protein interaction (PPI) network was constructed by STRING online software for further study, and the core genes were determined by Cytoscape software and KEGG pathway enrichment analysis. The clustering heat map was drawn by Excel software to verify its accuracy. In addition, we used the University of Alabama at Birmingham Cancer (UALCAN) website to analyze the expression of core genes in P53 mutation status, confirmed the expression of crucial core genes in lung cancer tissues with Gene Expression Profiling Interactive Analysis (GEPIA) and GEPIA2 online software, and evaluated their prognostic value in lung cancer patients with the Kaplan-Meier online plotter tool. Results: CHEK1, CCNB1, CCNB2, and CDK1 were selected. The expression levels of these four genes in lung cancer tissues were significantly higher than those in normal tissues. Their increased expression was negatively correlated with lung cancer patients (including LUAD and LUSC) prognosis and survival rate. Conclusion: CHEK1, CCNB1, CCNB2, and CDK1 are the critical core genes of lung cancer and are highly expressed in lung cancer. They are negatively correlated with the prognosis of lung cancer patients (including LUAD and LUSC) and closely related to the formation and prediction of lung cancer. They are valuable predictors and may be predictive biomarkers of lung cancer.

Prediction Biomarkers Associated with Lymph Node Metastasis and Prognosis were Identified in Papillary Thyroid Carcinoma via Integrated Bioinformatics Analysis.

BACKGROUND: Prediction biomarkers associated with prognosis and lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) are needed to facilitate clinicians in choosing appropriate therapies. OBJECTIVE: We hope to identify key genes associated with LNM and prognosis in PTC. METHODS: GSE29265, GSE33630, GSE3467, GSE3678 and GSE58545 gene expression profiles were acquired from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between PTC tissues and normal thyroid tissues were selected with the GEO2R tool, and common DEGs among the five datasets were integrated with Venn software online. A proteinprotein interaction (PPI) network of the common DEGs was visualized. We analyzed the PPI network and determined core genes using the Cytoscape software. Furthermore, we employed UALCAN to verify the expression and promoter methylation status of the core genes in thyroid carcinoma (THCA). Additionally, the Kaplan-Meier plotter online tool was used to analyze the relationship between overall survival and core gene expressions in THCA. RESULTS: TNS3, DUSP6, DUSP4 and PTPRE were identified as core genes. Expression of these 4 genes and the promoter methylation status of DUSP4 and PTPRE were strongly associated with LNM (P<0.05). High expression of 3 genes (DUSP6, DUSP4 and PTPRE) was related to a significantly better survival than low expression of the 3 genes in THCA. In contrast, high TNS3 expression was related to significantly worse survival (P<0.05). CONCLUSION: TNS3, DUSP6, DUSP4, PTPRE and DUSP4 and PTPRE promoter methylation status might be useful predictive biomarkers of LNM in PTC. Additionally, these genes may be prognostic biomarkers in PTC.

Contemporary Chinese centenarians: Health profiles, social support and relationships in Suixi County.

BACKGROUND: Centenarians are the fastest growing population worldwide. However, this group has been less studied in developing countries. Contemporary centenarians in China have experienced many ups and downs due to historical reasons, which may have resulted in a population with different characteristics from those in other countries. This study aimed to investigate the current sociodemographic characteristics, health profiles, and social relationships of Chinese centenarians. METHODS: We conducted face-to-face surveys in April 2017 with centenarian residents in Suixi County, the first "International Healthy Longevity Area" in China. A total of 100 centenarians were involved, including 67 females and 33 males. Information for socioeconomic and demographics characteristics, quality of life (physical, cognitive, and psychological function), and social support and relationships was collected. Sex differences in each measure were examined. RESULTS: We find that good self-reported health, good life satisfaction, intact memory function, independence, and unsatisfied healthcare needs were reported by 24.4%, 45.9%, 31.6%, 46.3%, and 33.4% of the respondents respectively. Subjective symptoms among males were less prevalent (p < 0.05). There were no statistical significant sex differences in cognitive and psychological function. The major source of care provision has been family. Generally, the centenarians had intimate relationships within families but maintained distant relationships with friends and communities. CONCLUSION: Our results bring attention to family-based care to provide informal care, and health education to promote healthy behaviors and healthcare utilization, for the oldest-old in China. The findings also imply a crucial role of good relationships with family in exceptional longevity.

Enhanced expression of SETDB1 possesses prognostic value and promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma.

SETDB1, an H3K9­specific histone methyltransferase, has been described as a repressed transcription marker which triggers tumorigenesis of many types of human cancer. However, there are few studies elucidating the relationship between SETDB1 and nasopharyngeal carcinoma. In the present study, we confirmed that SETDB1 exhibited higher expression levels in nasopharyngeal carcinoma (NPC) tissues and cell lines, compared to these levels in non­tumor tissues and a normal human nasopharyngeal epithelial cell line. Kaplan­Meier analysis showed that higher SETDB1 expression indicated an unfavorable prognosis for NPC patients, making it an independent prognostic factor for NPC in the COX proportional hazards model. In vitro functional studies revealed that upregulation of SETDB1 expression in CNE1 cells promoted cell proliferation, possibly through cell cycle G1/S phase transition. Moreover, it also enhanced cell migration and invasion ability. Downregulation of SETDB1 expression in 5­8F cells resulted in the opposite response. Overall, the findings indicated that increased expression of SETDB1 may predict poor overall survival and the malignant phenotype of NPC.

[Comparison of dyslipidemia prevalence between Korean and Han populations in Yanbian state].

OBJECTIVE: To compare the lipid levels, dyslipidemia prevalence and the influencing factors between Korean and Han nationalities in Yanbian state. METHODS: A population-based cross-sectional study was conducted. Totally 3011 subjects, ranging from 30 to 70 years old, were included. Height, weight, waist and hip circumference, serum lipids were measured. RESULTS: The HDL-C concentration of male and female Korean (1.04 +/- 0.45 mmol/L and 1.07 +/- 0.43 mmol/L, respectively) was significantly lower than those of Han (1.16 +/- 0.52 mmol/L and 1.19 +/- 0.56 mmol/L, F = 14.423 and 20.827; P < 0.001). The TG concentration of male Korean (2.10 +/- 2.08 mmol/L) was significantly higher than that of Han male (1.72 +/- 1.73 mmol/L, F = 13.543; P < 0.001) and the prevalence of high triglyceride among male Korean (23.3%) was also significantly higher than that of male Han (15.0%, chi2 = 12,720; P < 0.001). However, the prevalence of high total cholesterol among male Korean (2.3%) was significantly lower than that of Han male (5.2%, chi2 = 6.639; P < 0.01). The prevalence of high TC and TG among female Korean (6.7%) was significantly higher than those of female Han (4.1%, chi2 = 6.394; P<0.05). The crude rate of dyslipidemia of Korean was 31.5%, while that of Han was 24.4%, and the age-adjusted prevalence was 28.7% and 23.0%, respectively, which showed significant ethnic differences in male. The crude rate of dyslipidemia of Korean was 28.9%, while that of Han was 21.7%, and the age-adjusted prevalence was 21.5% and 20.5%, respectively, which also showed significant ethnic differences in female. The prevalence of dyslipidemia was positively correlated with sex, age, WHR, WHtR, and nationality. CONCLUSION: There were significant differences in the lipid profiles and the prevalence of dyslipidemia between Korean and Han nationalities. Sex, age,WHR, WHtR, and nationality in this state should be risk factors of the dyslipidemia.