ABSTRACT
Drug-resistant tuberculosis (TB), which results mainly from the selection of naturally resistant strains of Mycobacterium tuberculosis (MTB) due to mismanaged treatment, poses a severe challenge to the global control of TB. Therefore, screening novel and unique drug targets against this pathogen is urgently needed. The metabolic pathways of Homo sapiens and MTB were compared using the Kyoto Encyclopedia of Genes and Genomes tool, and further, the proteins that are involved in the metabolic pathways of MTB were subtracted and proceeded to protein-protein interaction network analysis, subcellular localization, drug ability testing, and gene ontology. The study aims to identify enzymes for the unique pathways for further screening to determine the feasibility of the therapeutic targets. The qualitative characteristics of 28 proteins identified as drug target candidates were studied. The results showed that 12 were cytoplasmic, 2 were extracellular, 12 were transmembrane, and 3 were unknown. Furthermore, druggability analysis revealed 14 druggable proteins, of which 12 were novel and responsible for MTB peptidoglycan and lysine biosynthesis. The novel targets obtained in this study are used to develop antimicrobial treatments against pathogenic bacteria. Future studies should further shed light on the clinical implementation to identify antimicrobial therapies against MTB.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is an infectious disease with approximately 517 million confirmed cases, with the average number of cases revealing that patients recover immediately without hospitalization. However, several other cases found that patients still experience various symptoms after 3-12 weeks, which is known as a long COVID syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can activate nuclear factor kappa beta (NF-κß) and unbind the nuclear factor erythroid 2-related factor 2 (Nrf2) with Kelch-like ECH-associated protein 1 (Keap1), causing inhibition of Nrf2, which has an important role in antioxidant response and redox homeostasis. Disrupting the Keap1-Nrf2 pathway enhances Nrf2 activity, and has been identified as a vital approach for the prevention of oxidative stress and inflammation. Hence, natural antioxidants from various sources have been identified as a promising strategy to prevent oxidative stress, which plays a role in reducing the long COVID-19 symptoms. Oxygen-rich natural antioxidant compounds provide an effective Nrf2 activation effect that interact with the conserved amino acid residues in the Keap1-binding pocket, such as Ser602, Ser363, Ser508, and Ser555. In this review, the benefits of various natural antioxidant compounds that can modulate the Nrf2 signaling pathway, which is critical in reducing and curing long COVID-19, are highlighted and discussed.
ABSTRACT
Background: A prophylactic and immunotherapeutic vaccine for Mycobacterium tuberculosis (MTB) and SARS-CoV-2 coinfection needs to be developed for a proactive and effective therapeutic approach. Therefore, this study aims to use immunoinformatics to design a multi-epitope vaccine for protection against MTB and SARS-CoV-2 coinfection. Methods: The bioinformatic techniques were used to screen and construct potential epitopes from outer membrane protein A Rv0899 of MTB and spike glycoprotein of SARS-CoV-2 for B and T cells. The antigenicity, allergenicity, and several physiochemical properties of the developed multi-epitope vaccination were then evaluated. Additionally, molecular docking and normal mode analysis (NMA) were utilized in evaluating the vaccine's immunogenicity and complex stability. Results: Selected proteins and predicted epitopes suggest that the vaccine prediction can be helpful in the protection against both SARS-CoV-2 and MTB coinfection. Through docking molecular and NMA, the vaccine-TLR4 protein interaction was predicted to be efficient with a high level of IgG, T-helper cells, T-cytotoxic cells, andIFN-γ. Conclusion: This epitope-based vaccine is a potentially attractive tool for SARS-CoV-2 and MTB coinfection vaccine development.
ABSTRACT
AIM: The aim of this study was to investigate the sensitivity of the trajectory log file based quality assurance to detect potential errors such as MLC positioning and gantry positioning by comparing it with EPID measurement using the most commonly used criteria of 3%/3 mm. MATERIALS AND METHODS: An in-house program was used to modified plans using information from log files, which can then be used to recalculate a new dose distribution. The recalculated dose volume histograms (DVH) were compared with the originals to assess differences in target and critical organ dose. The dose according to the differences in DVH was also compared with dosimetry from an electronic portal imaging device. RESULTS: In all organs at risk (OARs) and planning target volumes (PTVs), there was a strong positive linear relationship between MLC positioning and dose error, in both IMRT and VMAT plans. However, gantry positioning errors exhibited little impact in VMAT delivery. For the ten clinical cases, no significant correlations were found between gamma passing rates under the criteria of 3%/3 mm for the composite dose and the mean dose error in DVH (r < 0.3, P > 0.05); however, a significant positive correlation was found between the gamma passing rate of 3%/3 mm (%) averaged over all fields and the mean dose error in the DVH of the VMAT plans (r = 0.59, P < 0.001). CONCLUSIONS: This study has successfully shown the sensitivity of the trajectory log file to detect the impact of systematic MLC errors and random errors in dose delivery and analyzed the correlation of gamma passing rates with DVH.
