BioMed Research International最新文献

{"title":"Outbreak Response to Circulating Vaccine-Derived Poliovirus in Three Northern Regions of Ghana, 2019.","authors":"John Kofi Odoom, Emmanuel Kofi Dzotse, Nicholas Israel Nii-Trebi, David Opare, Ernest Akyereko, Keren Attiku, Ewurabena Oduma Duker, Miriam Eshun, Bismarck Banahene Boahene, Emmanuel Gberbi, Ekua Essumanma Houphouet, Stanley Diamenu, Michael Adjabeng, Joseph Asamoah-Frimpong, Donne Ameme, Joseph Kojo Larbi Opare, Evangeline Obodai","doi":"10.1155/2024/5515777","DOIUrl":"10.1155/2024/5515777","url":null,"abstract":"<p><p><b>Background:</b> Circulating Vaccine-Derived Poliovirus Type 2 (cVDPV2) was isolated in sewage and later in stool samples from children with acute flaccid paralysis (AFP) in northern Ghana. <b>Method:</b> A multidisciplinary and multisectoral team investigated this outbreak and reported on epidemiological and laboratory investigations. Sewage/wastewater samples were collected from the environment, while stool samples were collected from AFP/contact children under 5 years of age. The samples were processed for virus isolation, and positive isolates were sequenced. We also conducted a descriptive investigation involving a review of records, active case search, and Monovalent Oral Polio Vaccine 2 campaigns. Additionally, we interviewed caregivers about the vaccination status of their children, as well as their knowledge on polio prevention. Water quality, sanitation, hygiene practices, and health-seeking behaviours were also assessed. <b>Results:</b> A total of 18 cVDPV2 were confirmed in the three regions of Ghana during the outbreak in 2019-2020. All strains were genetically linked to a Nigerian cVDPV2 strain NIE-KWS-KSB-18-006HC29 that circulated in 2018. Evaluation of the surveillance system shows that officers have good knowledge of AFP and know how to collect samples, package them, and ship them to the laboratory. Few communities had access to potable water. Open defecation was common, and the water supply, sanitation, and hygiene practices of the communities were poor. <b>Conclusion:</b> The cVDPV2 outbreak represents the first time cVDPV2 has circulated in the country since Ghana embarked on the polio eradication program in 1996. However, with quality mOPV2 mop-up campaigns, a nationwide IPV catch-up campaign coupled with enhanced surveillance measures, transmission was interrupted.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"5515777"},"PeriodicalIF":2.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualization, Dynamicity, and Collaborative Networking of Scientific Production on Visible Light and Skin Aging: A Scientometric Analysis.","authors":"Fran Espinoza-Carhuancho, Carlos Quispe-Vicuña, Cesar Mauricio-Vilchez, Diego Galarza-Valencia, Julia Medina, Josmel Pacheco-Mendoza, Frank Mayta-Tovalino","doi":"10.1155/2024/5589020","DOIUrl":"https://doi.org/10.1155/2024/5589020","url":null,"abstract":"<p><p><b>Purpose:</b> The purpose of this is to examine the visualization, dynamicity, and collaborative networking of scientific production on visible light (VL) and skin aging through scientometric analysis. <b>Materials and Methods:</b> This research consisted of a cross-sectional and descriptive design with a scientometric approach that examined the publication trends and collaborative patterns among authors and institutions from 2018 to 2023. A comprehensive search strategy was also employed by using specific keywords related to VL and skin aging. In this case, several indicators were employed, including scholarly output, view count, field-weighted citation impact (FWCI), and citation count. The analyses were performed by using SciVal software and R Studio version 4.3.2. <b>Results:</b> A total of 180 sources were identified, with 280 documents generated, indicating an annual growth rate of 6.72%. The documents, averaging 3.25 years in age, received an average of 12.14 citations, revealing their impact. Additionally, collaborations were evident, with a ratio of 5.6 coauthors per paper and 25.71% consisting of international collaborations. In terms of institutions, there were notable disparities in scholarly activities and impact metrics, highlighting the diversity of the research landscape. Meanwhile, journals, such as <i>Photodermatology, Photoimmunology and Photomedicine</i>, revealed a substantial impact (FWCI 2.05). Overall, the impact of the journals showed a general upward trend, reflecting dynamicity and variability over time. <b>Conclusion:</b> An annual growth rate of 6.72% was found, with 180 sources and 280 papers on VL and skin aging. Moreover, international collaborations, the positive impact in leading journals, and the distribution patterns identified through scientometric laws underscored the vitality and complexity of the field. These results offer valuable insights into guiding future research in this multidisciplinary field.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"5589020"},"PeriodicalIF":2.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating the Immunotherapeutic Potential of Vitamin E and Its Analogues in Cancer: A Comprehensive Narrative Review.","authors":"Nevvin Raaj Morgan, Premdass Ramdas, Saatheeyavaane Bhuvanendran, Ammu Kutty Radhakrishnan","doi":"10.1155/2024/5512422","DOIUrl":"https://doi.org/10.1155/2024/5512422","url":null,"abstract":"<p><p>Cancer is a disease resulting from uncontrolled cell division, which significantly contributes to human mortality rates. An alternative approach to cancer treatment, such as cancer immunotherapy, is needed as the existing chemotherapy and radiotherapy approaches target the cancer cells and healthy dividing cells. Vitamin E is a plant-derived lipid-soluble antioxidant with numerous health-promoting benefits, including anticancer and immunomodulatory properties. Vitamin E comprises eight natural isoforms: tocopherols (<i>α</i>, <i>β</i>, <i>δ</i>, and <i>γ</i>) and tocotrienols (<i>α</i>, <i>β</i>, <i>δ</i>, and <i>γ</i>). While initial research focused on the anticancer properties of <i>α</i>-tocopherol, there is growing interest in other natural forms and modified synthetic analogues of vitamin E due to their unique properties and enhanced anticancer effects. Hence, this review is aimed at outlining the effect of vitamin E and its analogues at various steps of the cancer-immunity cycle that can be used to stimulate anticancer immune responses.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"5512422"},"PeriodicalIF":2.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development, Statistical Optimization, and Characterization of Resveratrol-Containing Solid Lipid Nanoparticles (SLNs) and Determination of the Efficacy in Reducing Neurodegenerative Symptoms Related to Alzheimer's Disease: In Vitro and In Vivo Study.","authors":"Mohammad Amin Khishvand, Ehsan Mehrabani Yeganeh, Mohammad Zarei, Meysam Soleimani, Mojdeh Mohammadi, Reza Mahjub","doi":"10.1155/2024/7877265","DOIUrl":"https://doi.org/10.1155/2024/7877265","url":null,"abstract":"<p><p>Resveratrol (RSV), as a natural polyphenol exhibiting antioxidative properties, is studied in the treatment of neurodegenerative diseases. However, RSV has low oral bioavailability. In this study and in order to overcome the issue, RSV was encapsulated into the solid lipid nanoparticles (SLNs). In this study, RSV-loaded solid lipid nanoparticles (RSV-SLNs) were prepared by the solvent emulsification-evaporation technique, and their physicochemical properties were optimized using Box-Behnken response surface methodology. The morphology of the particles was evaluated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The neuroprotective effects of the nanoparticles were investigated in animal models using the Morris water maze (MWM). Then after, the rats were sacrificed, their brains were collected, and the extent of lipid peroxidase (LPO) as well as the level of reduced glutathione (GSH) were determined in the hippocampus section samples. Finally, the collected brain tissues were histologically studied. The particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), and drug loading (DL%) of the optimized nanoparticles were 104.5 ± 12.3 nm, 0.322 ± 0.11, -3.1 ± 0.15 mV, 72.9 ± 5.31% and 14.6 ± 0.53%, respectively. The microscopic images revealed spherically shaped and nonaggregated nanoparticles. The <i>in vivo</i> studies demonstrated higher efficiency of RSV-SLN in the reduction of escape latency time and improvement in the time spent in the target quadrant compared to free RSV. Moreover, it was demonstrated that RSV-SLN posed a higher potency in the reduction of LPO as well as elevation of the GSH levels in the brain samples. The histological studies revealed a decline in neural degeneration and an improvement in the CA1 pyramidal cell morphology. The obtained data revealed that RSV-SLNs caused more reduction in Alzheimer-related symptoms rather than free RSV.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"7877265"},"PeriodicalIF":2.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteolysis Assays With Conserved or Aminofluorescein-Labeled Red Blood Cells.","authors":"Mohamed K Al-Essa, Tamara Al-Qudah, Akram Kamal A Al Hadidi, Nida'a H Alshubbak","doi":"10.1155/2024/7919329","DOIUrl":"10.1155/2024/7919329","url":null,"abstract":"<p><p><b>Backgrounds:</b> Various physiological functions and reaction cascades, as well as disease progression in the living systems, are controlled by the activity of specific proteolytic enzymes. We conducted the study to evaluate protease activity by assessing peptide fragments from either conserved or labeled red blood cells (RBCs) with aminofluorescein (AF) in the reaction media. <b>Methods:</b> RBCs were incubated in media containing trypsin. Subsequently, the concentration of peptide fragments in the reaction media, resulted by the digestion with trypsin from conserved cells, was estimated by 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) as an amine-reactive fluorogenic reagent. In a second approach, we conjugated AF to the conserved RBCs and then exposed AF-labeled RBCs to trypsin. This was followed by directly measuring the fluorescence intensity (FI) in the reaction media to estimate the concentration of AF-labeled peptide fragments resulting from the enzyme's activity. <b>Results:</b> Show a concentration- and time-dependent increase in FIs, reflecting the activity of trypsin as a proteolytic enzyme. The FIs increased significantly by 4 to 5 folds in samples treated with different enzyme concentrations, and by over 11 folds after 2 h incubation in media containing a 50 <i>μ</i>L trypsin, as evidenced by CBQCA assays. <b>Conclusion:</b> These fast and affordable approaches could be applied with high reliability for the general estimation of protease activity in samples and customized for diagnostic purposes and prognostic evaluation in various diseases.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"7919329"},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review on Recent Advance of 3DP-Based Pediatric Drug Formulations.","authors":"Aychew Mekuriaw Tegegne, Kassahun Dires Ayenew, Muluken Nigatu Selam","doi":"10.1155/2024/4875984","DOIUrl":"10.1155/2024/4875984","url":null,"abstract":"<p><p>Three-dimensional printing (3DP) has emerged as a game-changing technology in the pharmaceutical industry, providing novel formulation development in the pharmaceutical sector as a whole, which improved patients' individualized therapy. The pediatric population is among the key targets for individualized therapy. Children are a diverse group that includes neonates, infants, and toddlers, each with unique physiological characteristics. Treatment adherence has a significant impact on safe and effective pharmacotherapy in the pediatric population. Improvement of therapeutic dosage forms that provide for the special demands of the pediatric population is a significant challenge for the pharmaceutical industry. Scientists have actively explored 3DP, a quick prototype manufacturing method that has emerged in recent years from many occupations due to its benefits of modest operation, excellent reproducibility, and vast adaptability. This review illuminates the most widely used 3DP technology and its application in the development of pediatric-friendly drug formulations. This 3DP technology allows optimization of pediatric dosage regimens and cases that require individualized treatment, such as geriatrics, renal impairment, liver impairment, critically ill, pregnancy populations, and drugs with nonlinear pharmacokinetics. The fast evolution of 3DP expertise, in addition to the introduction of pharmaceutical inks, has enormous promise for patient dosage form customization.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"4875984"},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physicochemical Characterization and Evaluation of the Suspending Properties of <i>Boswellia papyrifera</i> Gum in Metronidazole Benzoate Suspension.","authors":"Gebremariam Woldu, Tsegay Brhane, Gebre Teklemariam Demoz","doi":"10.1155/2024/8899359","DOIUrl":"https://doi.org/10.1155/2024/8899359","url":null,"abstract":"<p><p><b>Background:</b> Currently, many natural gums are extensively utilized as suspending agents in the formulation of pharmaceutical suspensions. They are easily available, nontoxic, biodegradable, and cost-effective to be used as pharmaceutical excipients. <b>Objective:</b> The present study was aimed at physicochemical characterization and evaluation of the suspending capacity of <i>Boswellia papyrifera</i> gum (BPG) in comparison with sodium carboxy methyl cellulose (SCMC) and tragacanth gum (TG). <b>Methods:</b> The extracted and powdered BPG was subjected to physicochemical properties such as micromeritics, solubility, swelling power, ash value, moisture content, conductivity, pH, and apparent viscosity using standard methods. Metronidazole benzoate suspensions were formulated using various concentrations of BPG, SCMC, and TG (1%-5% <i>w</i>/<i>v</i>). The apparent viscosity, flow rate, sedimentation volume, redispersibility number, pH, and drug content were studied as assessment parameters. <b>Results:</b> The micromeritic studies revealed that BPG exhibited good flow properties. There was also a significant increase in solubility and swelling power of the gum as a function of temperature. The gum had 2.78% ash value and 4.32% moisture content. Conductivity and apparent viscosity of the gum were found to be increased with concentration (<i>p</i> < 0.05). However, the apparent viscosity of BPG was decreased with shear rate (<i>p</i> < 0.05), rendering a pseudoplastic flow property of the gum, which is an ideal characteristic of suspending agents. The suspending capacity of the BPG was found to be comparable to SCMC, but higher than TG. Thus, it can be concluded that BPG could be used as the best alternative to natural and synthetic suspending agents.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"8899359"},"PeriodicalIF":2.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological Evaluation of a Polyherbal Formulation (18KHT01) and Validation of UPLC-DAD Method for Quality Control.","authors":"Prakash Raj Pandeya, Ramakanta Lamichhane, Gopal Lamichhane, Kyung-Hee Lee, Hyun-Ju Jung","doi":"10.1155/2024/1767618","DOIUrl":"https://doi.org/10.1155/2024/1767618","url":null,"abstract":"<p><p><b>Background:</b> 18KHT01 is a novel synergistic composition of <i>Quercus acutissima</i>, <i>Camellia sinensis</i>, <i>Geranium thunbergii</i>, and a small portion of <i>Citrus limon</i>. Our previous report demonstrated that the 18KHT01 exhibits potent antiobesity effects, with synergistic antioxidant, antiadipogenic, and antiobesity activities in diet-induced obese mice. This study explores the toxicity profile and quality control parameters of the 18KHT01 formulation. <b>Methods:</b> Broad-spectrum acute and subacute oral toxicity studies were performed using male and female ICR mice. In order to simultaneous analysis of the 18KHT01 formulation, an ultraperformance liquid chromatography coupled with a diode array detector (UPLC-DAD) method was developed and validated using six marker compounds. <b>Results:</b> Acute oral toxicity evaluation of 18KHT01, administered at single high doses of 2, 2.5, 3, and 5 g/kg, identified 2 g/kg as the no-observed adverse effect level (NOAEL). The LD50 (50% lethal dose) and LD100 (100% lethal dose) of 18KHT01 for male ICR mice were 3.99 and 7.77 g/kg, and those for the female mice were 2.94 and 4.70 g/kg, respectively. In addition, a 30-day repeated dose oral subacute toxicity evaluation indicated that 18KHT01 is safe below 500 mg/kg/day for long-term administration in ICR mice of either sex. UPLC-DAD method validation revealed that each calibration curve for the marker compounds showed good linearity, as well as the validation parameters such as precision, specificity, and accuracy met the acceptance criteria. <b>Conclusion:</b> The present study evidenced the toxicological profile of 18KHT01 polyherbal formulation in mice as well as developed a simple, rapid, and accurate chromatographic method for quality control.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"1767618"},"PeriodicalIF":2.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APC and ZBTB2 May Mediate M2 Macrophage Infiltration to Promote the Development of Renal Fibrosis: A Bioinformatics Analysis.","authors":"Jianling Song, Ben Ke, Xiangdong Fang","doi":"10.1155/2024/5674711","DOIUrl":"10.1155/2024/5674711","url":null,"abstract":"<p><p><b>Background and Purpose:</b> The continuous accumulation of M2 macrophages may potentially contribute to the development of kidney fibrosis in chronic kidney disease (CKD). The purpose of this study was to analyze the infiltration of M2 macrophages in uremic patients and to seek new strategies to slow down the progression of renal fibrosis. <b>Methods:</b> We conducted a comprehensive search for expression data pertaining to uremic samples within the Gene Expression Omnibus (GEO) database, encompassing the time frame from 2010 to 2022. Control and uremic differentially expressed genes (DEGs) were identified. Immune cell infiltration was investigated by CIBERSORT and modules associated with M2 macrophage infiltration were identified by weighted gene coexpression network analysis (WGCNA). Consistent genes were identified using the least absolute shrinkage and selection operator (LASSO) and selection and visualization of the most relevant features (SVM-RFE) methods to search for overlapping genes. Receiver operating characteristic (ROC) curves were examined for the diagnostic value of candidate genes. Quantitative real-time PCR (qPCR) examined the expression levels of candidate genes obtained from uremic patients in M2 macrophage. <b>Results:</b> A total of 1298 DEGs were identified within the GSE37171 dataset. Significant enrichment of DEGs was observed in 20 biological processes (BP), 19 cellular components (CC), 6 molecular functions (MF), and 70 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. CIBERSORT analysis observed a significant increase in B-cell memory, dendritic cell activation, M0, M1, M2, and plasma cell numbers in uremic samples. We identified the 10 most interrelated genes. In particular, adenomatous polyposis coli (APC) and zinc finger and BTB structural domain 2 (ZBTB2) were adversely associated with the infiltration of M2 macrophages. Importantly, the expression levels of APC and ZBTB2 were far lower in M2 macrophages from uremic patients than those in healthy individuals. <b>Conclusion:</b> The development of renal fibrosis may be the result of M2 macrophage infiltration promoted by APC and ZBTB2.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"5674711"},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Mutagenesis and Inhibition of <i>Staphylococcus aureus</i> AgrA LytTR Domain Using Phenazine Scaffolds: Insight From a Biophysical Study.","authors":"Prince Manu, Prisca Baah Nketia, Priscilla Osei-Poku, Alexander Kwarteng","doi":"10.1155/2024/8843954","DOIUrl":"10.1155/2024/8843954","url":null,"abstract":"<p><p>Biofilm formation by <i>Staphylococcus aureus</i> is a major challenge in clinical settings due to its role in persistent infections. The AgrA protein, a key regulator in biofilm development, is a promising target for therapeutic intervention. This study investigates the antibiofilm potential of halogenated phenazine compounds by targeting AgrA and explores their molecular interactions to provide insights for drug development. We employed molecular docking, molecular dynamics simulations, and computational mutagenesis to evaluate the binding of halogenated phenazine compounds (C1 to C7, HP, and HP-14) to AgrA. Binding free energy analysis was performed to assess the affinity of these compounds for the AgrA-DNA complex. Additionally, the impact of these compounds on AgrA's structural conformation and salt bridge interactions was examined. The binding-free energy analysis revealed that all compounds enhance binding affinity compared to the Apo form of AgrA, which has a <i>Δ</i>G_bind of -80.75 kcal/mol. The strongest binding affinities were observed with compounds C7 (-113.84 kcal/mol), HP-14 (-115.23 kcal/mol), and HP (-112.28 kcal/mol), highlighting their effectiveness. Molecular dynamics simulations demonstrated that these compounds bind at the hydrophobic cleft of AgrA, disrupting essential salt bridge interactions between His174-Glu163 and His174-Glu226. This disruption led to structural conformational changes and reduced DNA binding affinity, aligning with experimental findings on biofilm inhibition. The halogenated phenazine compounds effectively inhibit biofilm formation by targeting AgrA, disrupting its DNA-binding function. The study supports the potential of these compounds as antibiofilm agents and provides a foundation for rational drug design targeting the AgrA-DNA interaction. Future research should focus on further optimizing these lead compounds and exploring additional active sites on AgrA to develop novel treatments for biofilm-associated infections.</p>","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"2024 ","pages":"8843954"},"PeriodicalIF":2.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}