Analysis of Key Genes and miRNA-mRNA Networks Associated with Glucocorticoids Treatment in Chronic Obstructive Pulmonary Disease.

Background: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear. Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained. Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated. Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated. Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.

Development of Acridone Derivatives: Targeting c-MYC Transcription in Triple-Negative Breast Cancer with Inhibitory Potential.

Breast cancer, especially the aggressive triple-negative subtype, poses a serious health threat to women. Unfortunately, effective targets are lacking, leading to a grim prognosis. Research highlights the crucial role of c-MYC overexpression in this form of cancer. Current inhibitors targeting c-MYC focus on stabilizing its G-quadruplex (G4) structure in the promoter region. They can inhibit the expression of c-MYC, which is highly expressed in triple-negative breast cancer (TNBC), and then regulate the apoptosis of breast cancer cells induced by intracellular ROS. However, the clinical prospects for the application of such inhibitors are not promising. In this research, we designed and synthesized 29 acridone derivatives. These compounds were assessed for their impact on intracellular ROS levels and cell activity, followed by comprehensive QSAR analysis and molecular docking. Compound N8 stood out, significantly increasing ROS levels and demonstrating potent anti-tumor activity in the TNBC cell line, with excellent selectivity shown in the docking results. This study suggests that acridone derivatives could stabilize the c-MYC G4 structure. Among these compounds, the small molecule N8 shows promising effects and deserves further investigation.

Time course of inflammatory response after renal artery stenting in patients with atherosclerotic renal stenosis.

BACKGROUND: Inflammatory response has been demonstrated in patients with coronary artery disease after percutaneous coronary intervention (PCI). Such response following renal artery stenting has not yet been established, however, in patients with atherosclerotic renal artery stenosis. METHODS: A total of 44 patients were enrolled in this study. Of them, 22 patients with atherosclerotic renal artery stenosis received renal angioplasty with stent (group A, mean age 51+/-8 years), and 22 patients with age- and gender-matched underwent renal angiography for diagnostic purpose as a control group (group B, age 50+/-8 years). The peripheral blood samples were taken immediately before the procedure, 1, 6 and 24 h after the procedure in both groups. The concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured using ELISA. RESULTS: The result showed that there was no difference in clinical characteristics and baseline levels of CRP and IL-6 between the groups. The IL-6 increased in the first hour (before: 5.8+/-3 pg/ml; 1 h: 8.6+/-5 pg/ml, p<0.01), lasted at 6 h (12.2+/-8 pg/ml), returned to baseline at 24 h (5.4+/-3 pg/ml) in group A. The CRP did not changed at the first hour after stenting, but mean CRP increased from 0.30+/-0.09 to 0.37+/-0.15 mg/dl at 6 h (p<0.05), and peaked at 24 h (0.43+/-0.18 mg/dl, p<0.001 compared with baseline and control) after stenting in group A, while no such changes were observed in group B (p>0.05 at different time points compared with baseline and group B, respectively). CONCLUSIONS: The data indicated that renal artery stenting could trigger inflammatory response by evidence of increased plasma levels of CRP and IL-6. IL-6, however, was an early initiator of inflammatory cytokine, and CRP was a later marker of systemic inflammatory response to renal artery stenting.

A pedigree analysis of familial hypercholesterolemia in monozygote twin brothers.

The current study was designed to investigate the features of a family with familial hypercholesterolemia (FH). Twenty members of 3 generations in a family with hypercholesterolemia were enrolled in the study. The data collected were from clinical observation and subjected to pedigree analysis. The proband was a 41-year-old male who suffered from angina pectoris with multi-vessel stenosis of coronary arteries at the age of 40. Among 20 members, 8 individuals had FH in this family with a total incidence of 40% (54.5% [6/11] in male and 22.2% [2/9] in female). The serum total cholesterol level was increased in childhood from 7.1 to 10.8 mmol/L and tended to increase with increasing age. In addition, the level of total cholesterol was increased in monozygote twin brothers and their offspring in the family. This pedigree analysis showed that FH appears to be a hereditary disease of autosomal dominance, and attention should be paid, especially in the only son or daughter society of China.