Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches

Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro275, Trp258, Glu225, and Gly259 during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM

Phytochemicals-based β-amyloid cleaving enzyme-1 and MAO-B inhibitors for the treatment of Alzheimer’s disease: molecular simulations-based predictions

Alzheimer’s disease (AD) is among the highly prevalent neurodegenerative disorder of the aging brain and is allied with cognitive and behavioral abnormalities. Unfortunately, there is very limited drug discovery for the effective management of AD, and the clinically approved drugs have limited efficacy. Consequently, there is an immediate demand for the development of new compounds that have the ability to act as multitarget-directed ligands (MTDLs). As major pathological targets of the disease, the current study aimed to investigate lead natural bioactive compounds including apigenin, epigallocatechin-3-gallate, berberine, curcumin, genistein, luteolin, quercetin, resveratrol for their inhibitory potentials against β-amyloid cleaving enzyme-1 (BACE1) and monoamine oxidase-B (MAO-B) enzymes. The study compounds were docked against the target enzymes (MAO-B and BACE1) using MOE software and subsequent molecular dynamics simulations (MDS) studies. The molecular docking analysis revealed that these phytochemicals (MTDLs) showed good interactions with the target enzymes as compared to the reference inhibitors. Among these eight phytocompounds, the epigallocatechin-3-gallate compound was an active inhibitor against both drug targets, with the highest docking scores and good interactions with the active residues of the enzymes. Furthermore, the docking result of the active one inhibitor in complex with the target enzymes (epigallocatechin-3-gallate/BACE1, epigallocatechin-3-gallate/MAO-B, reference/BACE1 and reference/MAO-B) were further validated by MDS. According to the findings of our study, epigallocatechin-3-gallate has the potential to be a candidate for use in the treatment of neurological illnesses like AD. This compound has MTDL potential and may be exploited to create new compounds with disease-modifying features. Communicated by Ramaswamy H. Sarma</p

COVID-19 Vaccine Acceptance and Hesitancy among Migrants, Refugees, and Foreign Workers: A Systematic Review and Meta-Analysis

Despite the effectiveness of current vaccines in reducing the spread and severity of SARS-CoV-2 infections, many people, including migrants, refugees, and foreign workers, are hesitant to be vaccinated. This systematic review and meta-analysis (SRMA) was conducted to determine the pooled prevalence estimate of the acceptance and hesitancy rates of the COVID-19 vaccine among these populations. A comprehensive search of the peer-reviewed literature indexed in PubMed, Scopus, Science Direct, and Web of Science databases was conducted. Initially, 797 potential records were identified, of which 19 articles met the inclusion criteria. A meta-analysis of proportions using data from 14 studies revealed that the overall acceptance rate of COVID vaccination among 29,152 subjects was 56.7% (95% CI: 44.9–68.5%), while the prevalence of vaccine hesitancy among 26,154 migrants reported in 12 studies was estimated to be 31.7% (95% CI: 44.9–68.5%). The acceptance rate for the COVID-19 vaccination first declined from 77.3% in 2020 to 52.9% in 2021 and then slightly increased to 56.1% in 2022. The most frequent factors influencing vaccine hesitancy were worries about vaccine efficacy and safety. Intensive vaccination campaigns should be implemented to raise vaccination awareness among migrants, which will increase the acceptance rate for the COVID-19 vaccine and result in herd immunity