Computational Insights into Captopril's Inhibitory Potential Against MMP9 and LCN2 in Bladder Cancer: Implications for Therapeutic Application.

Objectives: Captopril is a commonly used therapeutic agent in the management of renovascular hypertension (high blood pressure), congestive heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy. Captopril has been found to interact with proteins that are significantly associated with bladder cancer (BLCA), suggesting that it could be a potential medication for BLCA patients with concurrent hypertension. Methods: DrugBank 5.0 was utilized to identify the direct protein targets (DPTs) of captopril. STRING was used to analyze the multiple protein interactions. TNMPlot was used for comparing gene expression in normal, tumor, and metastatic tissue. Then, docking with target proteins was done using Autodock. Molecular dynamics simulations were applied for estimate the diffusion coefficients and mean-square displacements in materials. Results: Among all these proteins, MMP9 is observed to be an overexpressed gene in BLCA and its increased expression is linked to reduced survival in patients. Our findings indicate that captopril effectively inhibits both the wild type and common mutated forms of MMP9 in BLCA. Furthermore, the LCN2 gene, which is also overexpressed in BLCA, interacts with captopril-associated proteins. The overexpression of LCN2 is similarly associated with reduced survival in BLCA. Through molecular docking analysis, we have identified specific amino acid residues (Tyr179, Pro421, Tyr423, and Lys603) at the active pocket of MMP9, as well as Tyr78, Tyr106, Phe145, Lys147, and Lys156 at the active pocket of LCN2, with which captopril interacts. Thus, our data provide compelling evidence for the inhibitory potential of captopril against human proteins MMP9 and LCN2, both of which play crucial roles in BLCA. Conclusion: These discoveries present promising prospects for conducting subsequent validation studies both in vitro and in vivo, with the aim of assessing the suitability of captopril for treating BLCA patients, irrespective of their hypertension status, who exhibit elevated levels of MMP9 and LCN2 expression.

COVID-19 Infection in Pregnancy: A Review.

Coronavirus disease 2019 (COVID-19), which is a highly contagious viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a catastrophic effect on the world's demographics, resulting in more than 3.8 million deaths worldwide and establishing itself as the most serious global health crisis since the 1918 influenza pandemic. Several questions remain unanswered regarding the effects of COVID-19 disease during pregnancy. Although most infections are mild in high-risk populations, the severe disease frequently leads to intubation, intensive care unit admission, and, in some cases, death. Hormonal and physiological changes in the immune and respiratory systems, cardiovascular function, and coagulation may affect the progression of COVID-19 disease in pregnancy. However, the consequences of coronavirus infection on implantation, fetal growth and development, labor, and newborn health have yet to be determined, and, consequently, a coordinated global effort is needed in this respect. Principles of management concerning COVID-19 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and co-infection, fetal and uterine contraction monitoring, prevention, and / or treatment of thromboembolism early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. This review focuses on COVID-19 during pregnancy, its management, and the area where further investigations are needed to reduce the risk to mothers and their newborns.

Isotopic evidence suggests different initial reaction mechanisms for anaerobic benzene biodegradation.

The initial metabolic reactions for anaerobic benzene biodegradation remain uncharacterized. Isotopic data for carbon and hydrogen fractionation from nitrate-reducing, sulfate-reducing, and methanogenic benzene-degrading enrichment cultures and phylogenic information were used to investigate the initial reaction step in anaerobic benzene biodegradation. Dual parameter plots of carbon and hydrogen isotopic data (deltadelta2H/ deltadelta13C) from each culture were linear, suggesting a consistent reaction mechanism as degradation proceeded. Methanogenic and sulfate-reducing cultures showed consistently higher slopes (m = 29 +/- 2) compared to nitrate-reducing cultures (m = 13 +/- 2) providing evidence for different initial reaction mechanisms. Phylogenetic analyses confirmed that culture conditions were strictly anaerobic, precluding any involvement of molecular oxygen in the observed differences. Using published kinetic data, we explored the possibility of attributing such slopes to reaction mechanisms. The higher slopes found under methanogenic and sulfate-reducing conditions suggest against an alkylation mechanism for these cultures. Observed differences between the methanogenic and nitrate-reducing cultures may not represent distinct reactions of different bonds, but rather subtle differences in relative reaction kinetics. Additional mechanistic conclusions could not be made because kinetic isotope effect data for carboxylation and other putative mechanisms are not available.