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Background Bryonia alba extract is a well-known drug which is being utilized as phytomedicines and homoeopathic preparations since more than two centuries. This medicine is frequently used in clinical practice for flu-like conditions, respiratory tract infections, and gastrointestinal diseases, as evidenced by old literature and historical records. The plant contains Bryonicin, Bryonolic acid, Bryodin, Cucurbitacin, etc. The alkaloids in Bryonia alba have been discovered to be a powerful heme-oxygenase-1 inhibitor, which could help reduce oxidative stress during SARS-CoV-2 pathogenesis. During three waves of SARS-CoV-2, extracts of Bryonia alba were used; however, the actual scientific explanation for its mechanism of action is still unknown. In this experiment, we studied cytokine changes by diluted Bryonia alba extract in Delta SARS-CoV-2 spike protein RBD-induced pathogenesis, in fertilized chick ( Gallus gallus domesticus ) embryos. Results The recombinant Delta SARS-CoV-2 spike RBD protein was inoculated in 14-day-old chick ( Gallus gallus domesticus ) embryos along with control, pre-, and post-treatment sets with diluted Bryonia extract. After 48 h, allantoic fluids were collected and stored at – 20 °C for study of different cytokines. Histological changes of the liver were also studied in each animal. Diluted Bryonia extract upregulated IFN-α and IL-10 markedly. In pre-treatment set, IFN-α, IL-8, IL-10, and IL-1β were markedly decreased, while in the post-treatment set IL-6, IL-10, IL-8, and TGFβ1 were significantly decreased, with a tendency of more anti-inflammatory surge than pro-inflammatory cytokines. Conclusions This experiment indicated an immunomodulatory role of diluted ethanolic extract of Bryonia particularly in the post-treatment set, decreasing pro-inflammatory cytokines with beneficial effect.

Abstract Efflux pump-mediated drug resistance in bacteria is a common occurrence effective for the general survival of the organism. The Mycobacterium tuberculosis genome has an abundance of adenosine triphosphate (ATP) dependent cassette transporter genes but only a handful of them are documented for their contribution to drug resistance. In this study, we inspected the potential of an ABC transporter Rv1273c from M. tuberculosis as a multidrug efflux pump and a contributor to intrinsic drug resistance. Expression of Rv1273c in Escherichia coli and M. smegmatis conferred tolerance to various structurally unrelated antibiotics. Lower accumulation of fluoroquinolones in intact E. coli and M. smegmatis cells expressing the transporter implied its active efflux activity. Energy-dependent efflux by Rv1273c was observed in real time using the lipophilic dye Nile Red. Expression of Rv1273c also resulted in an increase in biofilm formation by E. coli and M. smegmatis cells. Overall, the results indicate the possibility that Rv1273c might be a multidrug transporter with a wide substrate range and a probable contributor to biofilm formation. Functional characterization of Rv1273c as a transporter involved in drug efflux.

Abstract Verona-integron-metallo-β-lactamase (VIM-2) is one of the most widespread class B β-lactamase responsible for β-lactam resistance. Although active-site residues help in metal binding, the residues nearing the active-site possess functional importance. Here, to decipher the role of such residues in the activity and stability of VIM-2, the residues E146, D182, N210, S207, and D213 were selected through in-silico analyses and substituted with alanine using site-directed mutagenesis. The effects of substitution mutations were assessed by comparing the changes in β-lactam susceptibility pattern of Escherichia coli host cell expressing VIM-2 and its mutated proteins. VIM-2_N210A enhanced the susceptibility of the host by ∼4–8 folds against penicillins and cephalosporins, while the expression of VIM-2_D182A radically increased the susceptibility of host. However, expression of VIM-2_E146A reduced the susceptibility of host by 2-fold. Further, proteins were purified to homogeneity, and VIM_N210A and VIM_D182A displayed reduced thermal stability than VIM-2. Moreover, in vitro catalytic efficiencies of VIM-2_D182A were drastically reduced against all the β-lactams tested whereas the same were moderately reduced for VIM-2_N210A. Conversely, the catalytic efficiency was marginally altered for VIM_E146A. Overall, we infer that both N210A and D182A substitutions negatively affect the performance of VIM-2 by influencing substrate specificity and stability, respectively. Non active-site residue mutations affect VIM-2 β-lactamase activity.