Even with substantial advances in cardiovascular therapy, the morbidity and mortality rates of diabetic cardiomyopathy (DCM) continually increase. Hence, a feasible therapeutic approach is urgently needed. Objectives. This work is aimed at systemically reviewing literature and addressing cell targets in DCM through the possible cardioprotection of G. lucidum through its antioxidant effects by using the Open Targets Platform (OTP) website. Methods. The OTP website version of 19.11 was accessed in December 2019 to identify the studies in DCM involving G. lucidum. Results. Among the 157 cell targets associated with DCM, the mammalian target of rapamycin (mTOR) was shared by all evidence, drug, and text mining data with 0.08 score association. mTOR also had the highest score association 0.1 with autophagy in DCM. Among the 1731 studies of indexed PubMed articles on G. lucidum published between 1985 and 2019, 33 addressed the antioxidant effects of G. lucidum and its molecular signal pathways involving oxidative stress and therefore were included in the current work. Conclusion. mTOR is one of the targets by DCM and can be inhibited by the antioxidative properties of G. lucidum directly via scavenging radicals and indirectly via modulating mTOR signal pathways such as Wnt signaling pathway, Erk1/2 signaling, and NF-κB pathways.
AT-rich interaction domain 1A (ARID1A) is a tumor suppressor gene that mutates in several cancer types, including breast cancer, ovarian cancer, and colorectal cancer (CRC). In colon adenocarcinoma (COAD), the low expression of ARID1A was reported but the molecular reason is unclear. We noticed that ARID1A low expression was associated with increased levels of miR-185 in the COAD. Therefore, this study aims to explore ncRNA-dependent mechanism that regulates ARID1A expression in COAD regarding miR-185. The expression of ARID1A was tested in COAD cell line under the effect of miR-185 mimics compared with inhibitor. The molecular features associated with loss of ARID1A and its association with tumor prognosis were analyzed using multi-platform data from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) to identify potential signaling pathways associated with ARID1A alterations in colon cancer. Kaplan-Meier survival curve showed that a low level of ARID1A was closely related to low survival rate in patients with COAD. Results showed that inhibiting miR-185 expression in the COAD cell line significantly restored the expression of ARID1A. Further, the increased expression of ARID1A significantly improved the prolonged overall survival of COAD. We noticed that there is a possible relationship between ARID1A high expression and tumor microenvironment infiltrating immune cells. Furthermore, the increase of ARID1A in tumor cells enhanced the response of inflammatory chemokines. In conclusion, this study demonstrates that ARID1A is a direct target of miR-185 in COAD that regulates the immune modulations in the microenvironment of COAD.
Objectives: The purpose of this study is to determine the therapeutic value of surgery in individuals with urinary bladder signet ring cell carcinoma (SRCC). Surgery has not been examined as a prognostic factor for urinary bladder cancer (SRCC). Materials and Methods: Using the Surveillance, Epidemiology, and End Results program (SEER), patients with urinary bladder SRCC who presented from 1975 to 2018 were included in a retrospective study. The effect of surgical therapy on cause-specific survival (CSS) and overall survival (OS) was examined using univariate and multivariate Cox regression models. We subdivided 595 patients with SRCC into 2 groups, as follows: 496 who underwent surgery; and 99 who did not undergo surgery. Results: Males had high predominance in all cases in both groups ( p = 0.04). Moderate and poor differentiation (III–IV) were observed in the majority of patients who underwent surgery (77.2 vs 58.6, p ⩽ 0.001) and had no insurance ( p ⩽ 0.001). By using KM, the OS and CSS of the surgery group were found to be significantly better than those of the non-surgery group ( p = 0.001,%) after adjusting for the variables of age, race, sex, primary site, grade, stage, lymph node removal, chemotherapy record, radiotherapy record, insurance, and marital status in the multivariate Cox proportional hazard model (hazard ratio [HR]= 0. 592; 95% confidence interval [CI] = 0.449–0.782; p = 0.0001). In comparison with chemotherapy and radiation, which resulted in poorer survival rates, surgery considerably improved survival outcomes in urinary bladder SRCC. The nomogram prediction model was built with C-index values of 0.70 and 73 for OS and CSS prediction, respectively. AUC in OS values were 0.77, 0.76, and 0.74, whereas AUC in CSS were 0.83, 0.80, and 0.79 for the 1-, 3-, and 5-year survival nomograms, respectively. Conclusion: Surgery was a significant independent predictor of bladder SRCC survival. Patients who underwent surgery had higher CSS and OS than people who did not undergo surgery. Surgery also led to better survival than the combination of the different treatment modalities.
Background: It is anticipated that there will be a large rise in the number of tumor diagnoses and mortality in those aged 65 and older over the course of upcoming decades. Immune checkpoint inhibitors, often known as ICIs, boost immune system activity by selectively targeting ICI genes. On the other hand, old age may be connected with unfavorable results. Methods: The Cancer Genome Atlas (TCGA) provided gene expression data from ccRCC tissue and key clinical variables. ICI gene databases were applied and verified using the GEO database. Results: We identified 14 ICI genes as risk gene signatures among 528 ccRCC patients using univariate and multivariable cox hazard models, and the elderly group was linked with poor survival. Then, by utilizing a new nomogram method, the TNFSF15 gene and age predicting values were estimated at one, three, and five years (85%, 81%, and 81%), respectively, and our age-related risk score was significant even after multivariable analysis (HR = 1.518, p = 0.009, CI = 1.1102.076). TNFSF15 gene expression was lower in elderly ccRCC patients (p = 0.0001). A negative connection between age and the TNFSF15 gene expression was discovered by correlation analysis (p = 0.0001). The verification of the gene by utilizing GEO (GSE167093) with 604 patients was obtained as external validation that showed significant differences in the TNFSF15 gene between young and elderly patients (p = 0.007). Additionally, the protein–protein interactions of the TNFSF15 gene with other ICI genes and aging-related genes was determined. In addition, the TNFSF15 expression was significantly correlated with pathological stages (p = 0.018). Furthermore, it was discovered that the biological processes of senescence, cellular senescence, the immune system, and many immune cell infiltration and immune function types are all closely tied. Conclusions: Along with the risk score evaluation, the ICI gene TNFSF15 was identified as a tumor suppressor gene related to inequalities in age survival and is associated with pathological stages and different immunity statuses. The aging responses of ccRCC patients and related gene expression need further investigation in order to identify potential therapeutic targets.
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