Objective: To investigate the differential expression of microRNA (miRNA) in patients with endometrial cancer and its relationship with prognosis and survival. Method: We used The Cancer Genome Atlas (TCGA) database to analyze differentially expressed miRNAs in endometrial cancer tissues and adjacent normal tissues. In addition, we successfully screened out key microRNAs to build nomogram models for predicting prognosis and we performed survival analysis on the key miRNAs as well. Result: We identified 187 differentially expressed miRNAs, which includes 134 up-regulated miRNAs and 53 down-regulated miRNAs. Further univariate Cox regression analysis screened out 47 significantly differentially expressed miRNAs and selected 12 miRNAs from which the prognostic nomogram model for ECA patients by LASSO analysis was constructed. Survival analysis showed that high expression of hsa-mir-138-2, hsa-mir-548f-1, hsa-mir-934, hsa-mir-940, and hsa-mir-4758 as well as low-expression of hsa-mir-146a, hsa-mir-3170, hsa-mir-3614, hsa-mir-3616, and hsa-mir-4687 are associated with poor prognosis in EC patients. However, significant correlations between the expressions levels of has-mir-876 and hsa-mir-1269a and patients’ prognosis are not found. Conclusion: Our study found that 12 significantly differentially expressed miRNAs might promote the proliferation, invasion, and metastasis of cancer cells by regulating the expression of upstream target genes, thereby affecting the prognosis of patients with endometrial cancer.

BACKGROUND: Vascular calcification is a major contributor to cardiovascular morbidity and mortality in diabetes and is driven in part by osteogenic reprogramming of vascular smooth muscle cells (SMCs). Diabetes is also associated with circadian rhythm disruption; however, how circadian regulators contribute to vascular calcification remains poorly understood. We investigated the role of the core circadian protein Bmal1 (basic helix-loop-helix ARNT-like protein 1) in diabetes-associated vascular calcification. METHODS: Bmal1 expression was examined in diabetic mouse aortas, human diabetic arterial tissues, and vascular SMCs exposed to high glucose. SMC-specific Bmal1 knockout mice were generated and subjected to low-dose streptozotocin-induced diabetes. Vascular calcification and stiffness were assessed by calcium staining and quantification, and pulse wave velocity. RNA sequencing, chromatin immunoprecipitation, luciferase reporter assay, and clustered regularly interspaced short palindromic repeats-clustered regularly interspaced short palindromic repeat–associated 9–mediated genome editing were used to define Bmal1-regulated molecular mechanisms. RESULTS: Bmal1, but not other circadian regulators, was selectively upregulated in diabetic arteries and vascular SMCs under hyperglycemic conditions. SMC-specific deletion of Bmal1 markedly attenuated diabetes-induced vascular calcification, reduced aortic stiffness, and suppressed osteogenic gene expression in vivo and in vitro. RNA-sequencing analysis revealed enrichment of Bmal1-dependent genes involved in osteogenic differentiation and extracellular matrix organization. Mechanistically, Bmal1 directly binds to an E-box motif in the Runx2 (Runt-related transcription factor 2) promoter, enhancing Runx2 transcription independently of canonical circadian pathways. Disruption of Bmal1 binding to the Runx2 promoter abolished Bmal1-induced Runx2 expression. CONCLUSIONS: Our findings identify Bmal1 as a key mediator of diabetes-induced vascular calcification through direct transcriptional regulation of Runx2 via a noncanonical circadian mechanism. These results reveal a previously unrecognized pathogenic role for Bmal1 in vascular disease and suggest that targeting dysregulated circadian factors may represent a novel therapeutic strategy for preventing vascular calcification in diabetes.

Genetic studies have linked EPHX2 (encoding soluble epoxide hydrolase, sEH) and PTGS2 (encoding cyclooxygenase-2, COX-2) to Alzheimer’s disease (AD). Elevated levels of sEH and COX-2 found in AD patients and animals suggest their involvement in neurodegeneration, glial activation, vascular dysfunction, and inflammation. This study evaluated the effects of a new dual sEH/COX-2 inhibitor, PTUPB, on cerebrovascular function and cognition in TgF344-AD rats. The rats received oral PTUPB (2 mg/kg/day) for 25 days. Body weight, plasma glucose, and HbA1c levels remained stable between PTUPB- and vehicle-treated AD rats. PTUPB significantly improved recognition memory in AD rats, as detected by the Novel Object Recognition test. Pressure myography showed that PTUPB restored myogenic responses and increased the distensibility of the middle cerebral arteries (MCAs) in AD rats. Acute PTUPB (0.1 and 1 μM) enhanced myogenic contraction in response to elevated perfusion pressure in AD MCAs, with minimal effects in wild-type vessels. Vehicle-treated AD rats displayed impaired functional hyperemia, whereas PTUPB (1 μM) significantly restored this response. Transcriptomic analysis of cerebral vascular smooth muscle cells from AD rats indicated that PTUPB influences genes related to contractility, extracellular matrix remodeling, inflammation, and oxidative stress. These results provide new evidence that dual inhibition of sEH and COX-2 improves cognition in AD, likely by enhancing myogenic response and increasing cerebral artery distensibility. Our findings highlight the potential of PTUPB as a therapeutic approach for cerebrovascular dysfunction in AD.

(1) Purpose: To compare and evaluate the immediate and long-term results of the use of various hernioplasties for the treatment of inguinal hernias after surgical treatment of prostate cancer; to determine the possibility of performing transabdominal preperitoneal (TAPP) hernioplasty and total extraperitoneal (eTEP) hernioplasty in patients with inguinal hernia during surgical treatment of prostate cancer. (2) Method: This study is a clinical analytical prospective study, without the use of randomization. The study included 220 patients with inguinal hernia, who were randomly divided into two groups (group A (n = 100) and group B (n = 120)). Patients in group A received eTEP, and those in group B received TAPP. The end points of the study were the results associated with the operation itself and the prognosis of the disease in the two groups. (3) Results: Group A: five patients had a scrotal hematoma, in 10 cases nosocomial pneumonia or infectious complications from the postoperative wound. The overall rate of early postoperative complications was 15%. In group B, the following postoperative complications were reported: one case of intestinal injury, six cases of acute urinary retention, eight cases of scrotal hematoma and 12 cases of nosocomial pneumonia or infectious complications from the postoperative wound were admitted. The overall incidence of early postoperative complications was 22.5%. There was no statistically significant difference in the incidence of postoperative complications between the two groups (χ² (3) = 2.54, p > 0.05). (4) Conclusion: During the analysis of the obtained results, no statistically significant difference was found in the duration of hospitalization, the volume of blood loss, the severity of pain syndrome, postoperative complication incidence and recurrence incidence (p > 0.05); however, the comparison groups differed in the duration of the operation: the operation time in group A was much longer compared to group B (p < 0.05).

Background: Age is the most important risk factor for coronary artery disease (CAD) independent of traditional risk factors. Aging induces classic pro-inflammatory and prothrombotic vascular phenotypic changes whose molecular mediators remain poorly understood. Medin is a common cleavage product protein that accumulates in vasculature with aging and shown to cause endothelial dysfunction. Its role in CAD is unknown. The study aimed to evaluate the effects of medin on human coronary artery endothelial cell (HCAEC) pro-inflammatory and prothrombotic activation and establish the relationship between medin and coronary atherosclerosis in human decedents. Methods: HCAECs were exposed to physiologic dose of medin (5 µM) for 20 hours and ribonucleic acid sequencing (RNAseq) with signaling pathway analyses and reverse transcription polymerase chain reaction of select pro-inflammatory and prothrombotic genes performed. Corresponding protein expression was measured by Western blot or enzyme linked immunosorbent assay in HCAECs exposed to medin (5 µM) without or with nuclear factor-κB (NFκB) inhibitor RO106-9920 (10 µM). Coronary arteries from 40 deceased individuals underwent immunohistochemistry and medin and plaque burden were quantified and their relationship evaluated. Results: RNAseq showed predominant pro-inflammatory gene expression changes induced by medin. HCAECs treated with medin showed increased phosphorylated NFκB, elevated protein expression of interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and plasminogen activator inhibitor (PAI)-1 and reduced protein expression of thrombomodulin; these changes were reversed by RO106-9920 co-treatment. In human tissues, coronary artery medin strongly correlated with plaque burden (R=0.76, p<0.0001) and coronary macrophage content (R=0.72, p<0.0001). Coronary arteries from decedents with myocardial infarction had higher medin than those without (5.53±2.67% versus 0.02±0.02%, p=0.0005). Conclusions: Medin induced NFκB-mediated endothelial cell pro-inflammatory and prothrombotic activation and was strongly associated with coronary plaque burden and inflammation. Medin is a novel candidate mediator linking aging and coronary atherosclerosis.