Oncoinformatic screening of the gene clusters involved in the HER2-positive breast cancer formation along with the in silico pharmacodynamic profiling of selective long-chain omega-3 fatty acids as the metastatic antagonists.

The HER2-positive patients occupy ~ 30% of the total breast cancer patients globally where no prevalent drugs are available to mitigate the frequent metastasis clinically except lapatinib and neratinib. This scarcity reinforced researchers' quest for new medications where natural substances are significantly considered. Valuing the aforementioned issues, this research aimed to study the ERBB2-mediated string networks that work behind the HER2-positive breast cancer formation regarding co-expression, gene regulation, GAMA-receptor-signaling pathway, cellular polarization, and signal inhibition. Following the overexpression, promotor methylation, and survivability profiles of ERBB2, the super docking position of HER2 was identified using the quantum tunneling algorithm. Supramolecular docking was conducted to study the target specificity of EPA and DHA fatty acids followed by a comprehensive molecular dynamic simulation (100 ns) to reveal the RMSD, RMSF, Rg, SASA, H-bonds, and MM/GBSA values. Finally, potential drug targets for EPA and DHA in breast cancer were constructed to determine the drug-protein interactions (DPI) at metabolic stages. Considering the values resulting from the combinational models of the oncoinformatic, pharmacodynamic, and metabolic parameters, long-chain omega-3 fatty acids like EPA and DHA can be considered as potential-targeted therapeutics for HER2-positive breast cancer treatment.

WGS-based screening of the co-chaperone protein DjlA-induced curved DNA binding protein A (CbpA) from a new multidrug-resistant zoonotic mastitis-causing Klebsiella pneumoniae strain: a novel molecular target of selective flavonoids.

The research aimed to establish a multidrug-resistant Klebsiella pneumoniae-induced genetic model for mastitis considering the alternative mechanisms of the DjlA-mediated CbpA protein regulation. The Whole Genome Sequencing of the newly isolated K. pneumoniae strain was conducted to annotate the frequently occurring antibiotic resistance and virulence factors following PCR and MALDI-TOF mass-spectrophotometry. Co-chaperon DjlA was identified and extracted via restriction digestion on PAGE. Based on the molecular string property analysis of different DnaJ and DnaK type genes, CbpA was identified to be regulated most by the DjlA protein during mastitis. Based on the quantum tunnel-cluster profiles, CbpA was modeled as a novel target for diversified biosynthetic, and chemosynthetic compounds. Pharmacokinetic and pharmacodynamic analyses were conducted to determine the maximal point-specificity of selective flavonoids in complexing with the CbpA macromolecule at molecular docking. The molecular dynamic simulation (100 ns) of each of the flavonoid-protein complexes was studied regarding the parameters RMSD, RMSF, Rg, SASA, MMGBSA, and intramolecular hydrogen bonds; where all of them resulted significantly. To ratify all the molecular dynamic simulation outputs, the potential stability of the flavonoids in complexing with CbpA can be remarked as Quercetin > Biochanin A > Kaempherol > Myricetin, which were all significant in comparison to the control Galangin. Finally, a comprehensive drug-gene interaction pathway for each of the flavonoids was developed to determine the simultaneous and quantitative-synergistic effects of different operons belonging to the DnaJ-type proteins on the metabolism of the tested pharmacophores in CbpA. Considering all the in vitro and in silico parameters, DjlA-mediated CbpA can be a novel target for the tested flavonoids as the potential therapeutics of mastitis as futuristic drugs.

Rising pharmaceutical innovation in the Global South: a landscape study.

BACKGROUND: There is growing interest in pharmaceutical innovation in low- and middle-income countries (LMICs), but information on existing activities, capacities, and outcomes is scarce. We mapped available data at the global level, and studied the national pharmaceutical innovation systems of Bangladesh and Colombia to shed light on pharmaceutical research and development (R&D) in the Global South, including challenges and prospects, to help fill existing knowledge gaps. METHODS: We gathered and analyzed data from three types of sources: literature, semi-structured interviews with key informants, and publicly available data on R&D funding, R&D scientific capacity measured by human resources, and clinical trial activities. RESULTS: Pharmaceutical R&D activities are occurring in many LMICs, but 16 countries have emerged as frontrunners. Investment in R&D in LMICs has increased in the past decade, particularly from middle-income countries (MICs). Capacity is also growing, with an increase in the number of research organizations and the amount of funding available from external sources. The total number of clinical trials and the proportion of trials in LMICs increased markedly, and there is also growing activity in the earlier, more innovative and riskier Phase 1 and 2 trials. Non-commercial entities comprise the majority of clinical trial funders and sponsors in LMICs. Finally, investments have borne fruit, as indicated by a number of innovative medicines developed in LMICs. The Bangladesh and Colombia country studies showed that there is still a need for both targeted R&D policies to strengthen capacities in the pharmaceutical sector, and more government support to overcome the challenges of a lack of funding and coordination among different actors. CONCLUSIONS: By triangulating between the data sources, it was possible to paint a broad picture of who was involved in pharmaceutical R&D in LMICs, in which particular countries, for which diseases, in which R&D phases, and with what results-as well as how these trends have changed over time. Prioritizing pharmaceutical R&D is an important strategy for better meeting health needs. The trendlines are promising, but focused attention is still needed to realize the potential for greater innovation in the Global South.