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The present study was aimed to delineate in vivo mechanisms of orally administered fisetin with special reference to mitochondrial dysfunction in lung tissues employing benzo(a)pyrene (B(a)P) as the model lung carcinogen. The recent revival of interest in the study of mitochondria has been stimulated by the evidence that genetic and/or metabolic alterations in this organelle lead to a variety of human diseases including cancer. These alterations could be either causative or contributing factors. Hence, the activities of mitochondrial-specific enzymes of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and tumor marker, carcinogenic embryonic antigen were analyzed in control and experimental groups of mice. The induction of apoptotic and anti-apoptotic proteins such as Bcl-2/Bax, cytochrome c, caspase-9 and caspase-3 was confirmed by the immunohistochemistry and Western blot analyses. Furthermore, transmission electron microscopy study of lung sections of B(a)P-induced mice showed the presence of phaemorphic cells with dense granules and increased mitochondria. All the aberrations were alleviated when the mice were treated with fisetin (25 mg/kg body weight). The results proved fisetin to be a very successful drug in combating the mitochondrial dysfunction in an experimental model of lung carcinogenesis induced by B(a)P.

The ability of extremely low, time‐varying electromagnetic field (EMF) to improve germination efficacy was studied in Foxtail millet (Setaria italica) seeds using response surface methodology. An optimal factorial central composite design was chosen to optimize the EMF with three critical factors, viz. frequency, intensity, and duration. The adequacy of the model and fitness was evaluated by analysis of variance and regression coefficients. This model suggested that the factors, frequency, and intensity had a significant impact on germination. Optimal conditions for germination were observed to be 10 Hz frequency, 30,007 nT intensity, and 30‐min duration with an observed germination percentage of 93.0, and a predicted germination percentage of 92.92. Magneto‐priming was found to increase the germination efficacy (15.66%), shoot length (27.78%), total seedling length (20.30%), seedling dry mass (26.49%), and water uptake (34.48% at 80 min) showing significant output when compared with the control and positive controls. Remarkable improvements were observed in germination parameters such as vigor index‐1 (39.14%), vigor index‐2 (46.28%), speed of germination (27.52%), and emergence index (12.50%). Magneto‐priming was found to reduce the levels of germination‐specific enzymes, viz. α‐amylase, protease, and dehydrogenase, while it enhanced the levels of antioxidant enzymes, viz. catalase (114.63%) and superoxide dismutase (19.62%), triggering fast germination and early vigor of seedlings. This study clearly showed that EMF priming significantly improved the germination effect and other characteristics of Foxtail millet seeds. Bioelectromagnetics. © 2020 Bioelectromagnetics Society

Discovery of a potent SARS-CoV-2 main protease (M pro ) inhibitor is the need of the hour to combat COVID-19. A total of 1000 protease-inhibitor-like compounds available in the ZINC database were screened by molecular docking with SARS-CoV-2 M pro and the top 2 lead compounds based on binding affinity were found to be 1,2,4 triazolo[1,5-a] pyrimidin-7-one compounds. We report these two compounds (ZINC000621278586 and ZINC000621285995) as potent SARS-CoV-2 M pro inhibitors with high affinity (<−9 kCal/mol) and less toxicity than Lopinavir and Nelfinavir positive controls. Both the lead compounds effectively interacted with the crucial active site amino acid residues His41, Cys145 and Glu166. The lead compounds satisfied all of the druglikeness rules and devoid of toxicity or mutagenicity. Molecular dynamics simulations showed that both lead 1 and lead 2 formed stable complexes with SARS-CoV-2 M pro as evidenced by the highly stable root mean square deviation (<0.23 nm), root mean square fluctuations (0.12 nm) and radius of gyration (2.2 nm) values. Molecular mechanics Poisson-Boltzmann surface area calculation revealed thermodynamically stable binding energies of −129.266 ± 2.428 kJ/mol and − 116.478 ± 3.502 kJ/mol for lead1 and lead2 with SARS-CoV-2 M pro , respectively.