Although osteoporosis is one of the most common chronic age-related diseases, there is currently no gold standard for treatment. Evidence suggests resveratrol, a natural polyphenolic compound, may be helpful in the treatment of osteoporosis and other diseases. However, the molecular mechanisms underlying the antiosteoporotic effects of resveratrol remain largely unknown. In the present study, KEGG pathway enrichment analysis of resveratrol-targeted genes identified 33 associated pathways, 12 of which were also involved in osteoporosis. In particular, the MDM2/p53 signaling pathway was identified as a potential key pathway among the shared pathways. In vitro experiments indicated that MDM2-mediated p53 degradation induced osteoblast differentiation, and resveratrol could partially reverse p53-dependent inhibition of osteogenic differentiation. These findings suggest resveratrol may alleviate osteoporosis at least in part by modulating the MDM2/p53 signaling pathway.

Systemic sclerosis (SSc) is a prototypic fibrotic disease characterized by localized or diffuse skin thickening and fibrosis. Tissue fibrosis is driven by myofibroblasts, and factors affecting myofibroblast activation may also be involved in the development of SSc. In this study, we examined molecular mechanisms underlying SSc by focusing on myofibroblast activation processes. Bioinformatics analysis conducted to identify differentially expressed miRNAs (DEMs) and genes (DEGs) revealed that microRNA-16-5p (miR-16-5p) was downregulated and NOTCH2 was upregulated in SSc patients. In vitro experiments confirmed that miR-16-5p was able to bind directly to NOTCH2 and inhibit myofibroblast activation. Moreover, miR-16-5p-dependent inhibition of NOTCH2 decreased collagen and α-SMA expression. MiR-16-5p downregulation and NOTCH2 upregulation was also confirmed in vivo in SSc patients, and NOTCH2 activation promoted fibrosis progression in vitro . These results indicate that miR-16-5p suppresses myofibroblast activation by suppressing NOTCH signaling.

The absence of a gold standard for treating pulmonary fibrosis makes its management challenging. We established a rat model to study the effect of resveratrol (Res) on bleomycin-induced pulmonary fibrosis. Rats were randomly divided into control, model, low-Res, middle-Res, high-Res, and dexamethasone groups and treated with various concentrations of these drugs. Rats showed typical features of pulmonary fibrosis; i.e., alveolitis, fibrous hyperplasia, and fibrosis on days 7, 14, and 28, respectively. Expression of HIF-1α and NF-κB was higher in the middle-Res, high-Res, and dexamethasone groups than in the control group, but was less than that in the model and low Res groups. We conclude that different levels of HIF-1α and NF-κB expression at different stages of pulmonary fibrosis in rats is positively correlated with the disease severity. Furthermore, resveratrol alleviates bleomycin-induced pulmonary fibrosis by suppressing HIF-1α and NF-κB expression, indicating its potential as a promising therapeutic drug candidate.

Background Lung adenocarcinoma (LUAD) is a type of non-small cell carcinoma. Its pathogenesis is being explored and there is no cure for the disease. Material/Methods The Gene Expression Omnibus (GEO) was searched to obtain data on expression of messenger RNA. GEO2R, an interactive web tool, was used to calculate the differentially expressed genes (DEGs) in LUAD. All the DEGs from different datasets were imported into VENNY 2.1 ( https://bioinfogp.cnb.csic.es/tools/venny/index.html ) to identify the intersection of the DEGs. An online analysis tool, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), was used to help understand the biological meaning of DEG enrichment in LUAD. Cytoscape 3.7.2 was used to perform centrality analysis and visualize hub genes and related networks. Furthermore, the prognostic value of the hub genes was evaluated with the Kaplan-Meier plotter survival analysis tool. Results The GEO database was used to obtain RNA sequencing information for LUAD and normal tissue from the GSE118370, GSE136043, and GSE140797 datasets. A total of 376 DEGs were identified from GSE118370, 248 were identified from GSE136403, and 718 DEGs were identified from GSE140797. The 10 genes with the highest degrees of expression – the hub genes – were CAV1, TEK, SLIT2, RHOJ, DGSX, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 . In addition, Kaplan-Meier survival evaluation showed that CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 were associated with favorable outcomes for LUAD. Conclusions CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 are hub genes in the DEG interaction network for LUAD and are involved in the development of and prognosis for the disease. The mechanisms underlying these genes should be the subject of further studies.

This study investigated whether long noncoding RNA interfering EIF3J antisense RNA1 (EIF3JAS1) could affect lung cancer A549 cells as well as the role of microRNA-330-5p (miR-330-5p) during this process. To this end, quantitative real-time polymerase chain reaction was used to measure EIF3J-AS1 and miR-330-5p expression in 39 lung cancer cases. Small interfering RNA targeting EIF3J-AS1 (si-EIF3J-AS1), as well as the miR-330-5p inhibitor, was transfected into lung cancer A549 cells. The outcomes of cell proliferation, clone formation, migration, invasion, and E- and N-cadherin expression were analyzed using CCK-8 kit, clone formation experiment, Transwell method, and Western blot. The targeted binding between EIF3J-AS1 and miR-330-5p was explored using the luciferase experiment. The results showed higher EIF3J-AS1 expression but lower miR-330-5p expression cancer tissues. Furthermore, interfering EIF3J-AS1 increased miR-330-5p and E-cadherin protein expression, leading to a reduction in the proliferation, clone formation, migration, invasion, and N-cadherin protein expression of lung cancer A549 cells. Meanwhile, Transfecting si-EIF3J-AS1 and the miR-330-5p inhibitor could increase the proliferation, clone formation, migration, invasion, and N-cadherin protein expression of lung cancer A549 cells, suggesting the targeted relationship of EIF3J-AS1 to miR-330-5p. In summary, EIF3J-AS1 was highly expressed in lung cancer tissues, and interfering EIF3J-AS1 inhibited the proliferation,migration, and invasion of A549 cells through negative regulation of miR-330-5p.