Resveratrol mitigates miR-212-3p mediated progression of diesel exhaust-induced pulmonary fibrosis by regulating SIRT1/FoxO3.

BACKGROUND: Diesel exhaust (DE) exposure contributes to the progression of chronic respiratory diseases and is associated with dysregulation of microRNA expression. The present study aims to investigate the involvement of miRNAs and target genes in DE-induced lung fibrosis. METHODS: C57BL/6 mice were divided into three groups. Group 1 mice were exposed to filtered air (Control). Group 2 mice were exposed to DE for 30 min per day, 5 days per week, for 8 weeks (DE). Group 3 mice received DE exposure along with resveratrol on alternate days for the last 2 weeks (DE + RES). Mice were sacrificed to isolate RNA from lung tissue for miRNA microarray profiling. Bronchoalveolar lavage fluid and lung tissues were collected for cell count and biochemical analysis. RESULTS: DE exposure resulted in differential expression of 28 miRNAs with fold change >2 (p < 0.05). The upregulated miR-212-3p was selected for further analysis. Consensus analysis revealed enrichment of SIRT1 in the FoxO pathway, along with a co-annotation of reduced body weight (p < 0.05). A549 cells transfected with a miR-212-3p inhibitor showed a dose-dependent increase in SIRT1 expression, indicating SIRT1 as a direct target. Treatment with resveratrol restored SIRT1 and miR-212-3p expression and led to a reduction in inflammatory cytokines (p < 0.05). The modulation of SIRT1 correlated negatively with macrophage infiltration, confirming its role in regulating cellular infiltration and lung inflammation. Fibronectin, alpha-SMA, and collagen levels were significantly decreased in DE + RES compared to DE group suggesting modulation of cellular functions and resolution of lung fibrosis. Furthermore, a significant decrease in FoxO3a and TGF-ß gene expressions was observed upon resveratrol administration thereby downregulating pro-fibrotic pathway. CONCLUSIONS: The present study demonstrates resveratrol treatment stabilizes SIRT1 gene expression by attenuating miR-212-3p in DE-exposed mice, leading to downregulation of TGF-ß and FoxO3a expressions. The study highlights the therapeutic role of resveratrol in the treatment of DE-induced pulmonary fibrosis.

Effect of Structural Variation on Spectral, NLO Properties, and Biological Activity of Pyrrole Hydrazones.

This paper describes spectral, non-linear optical (NLO), and biological activity variation of pyrrole hydrazones as a result of structural variation. In order to study structure-property variation, pyrrole hydrazones (3A, 3B, and 3C) were synthesized in both solid and solution phases. The grinding solvent-free method becomes rapid, easy, convenient, useful, sustainable, and eco-friendly green synthesis as compared to the classical solution phase reactions. The structure of pyrrole hydrazones has been elucidated by microanalysis and quantum chemical calculations. The intense emission at λem 521 nm (3A and 3B) and 617 nm (3C) in the visible (green and orange) region with Stokes shifts at 195, 160, and 282 nm reveals that the studied compounds work as good photoluminescent materials. All compounds show strong n-π* and charge transfer (π-π*) transitions in the UV-vis region with high extinction coefficients. In the studied systems (3A, 3B, and 3C), the orbital overlap between σ(NH-O) → σ*(NH-O) is found due to intra-molecular charge transfer. The first hyperpolarizabilities were found to be 48.83 × 10-30 esu for 3B and 63.89 × 10-30 esu for 3C, showing variation with structure. Their high values indicate more suitability for NLO application. Incorporation and/or change in position of electron-withdrawing groups increase the ß0 values of 3B and 3C compared to 3A. The ß value also increases monotonically as the polarity of the solvents increases. The red shift in N-H and C=O stretching Fourier-transform infrared bonds is due to the formation of dimers. The synthesized 3A, 3B, and 3C show good antimicrobial activity and are predicted to be potential antibacterial and antifungal drugs. The 3B has more molar refractivity (122.16 esu) than 3A and 3C and correlates well with the calculated binding affinity and experimental antimicrobial data.