Frontiers in Bioscience - Elite最新文献

{"title":"AI-driven hybrid ecological model for predicting oncolytic viral therapy dynamics","authors":"Abicumaran Uthamacumaran, Juri Kiyokawa, Hiroaki Wakimoto","doi":"10.1016/j.insi.2026.100258","DOIUrl":"https://doi.org/10.1016/j.insi.2026.100258","url":null,"abstract":"Oncolytic viral therapy (OVT) is an emerging precision therapy for aggressive and recurrent cancers. However, its clinical efficacy is hindered by the complexity of tumor-virus-immune interactions and the lack of predictive models for personalized treatment. This pilot study develops a data-driven, and AI-powered computational model combining time-delayed Generalized Lotka–Volterra (GLV) equations with advanced optimization algorithms, including Genetic Algorithms (GA), Differential Evolution (DE), and Reinforcement Learning (RL) to optimize OVT oscillations’ growth and damping. We hypothesize that the model can provide accurate, real-time predictions of OVT responses while identifying key biomarkers to enhance therapeutic efficacy. We demonstrate the model’s strong predictive accuracy (MSE <0.02, R 2 >0.82) and its capacity to identify experimentally validated biomarkers such as TNF, NF-kB, CD81, TRAF2, IL18, and BID, among other inflammatory cytokines and extracellular matrix reconstruction factors, despite being causally agnostic and unaware of specific experimental conditions or therapeutic combinations. Gene set enrichment analysis computationally identified pathway-level similarities between combined OVT and immune checkpoint blockade and photodynamic therapy, suggesting predictive convergence in immune signaling programs . To our knowledge, this is the first in silico integration of time-delay GLV predator–prey modeling with explainable AI for OVT predictions, recovering experimentally validated biomarkers in an unbiased, data-agnostic forecast. This hybrid model represents a significant step toward precision oncology and computational medicine, enabling longitudinal, adaptive treatment regimens, and the development of targeted immunotherapies based on molecular signatures, potentially improving patient outcomes in predictive medicine.","PeriodicalId":38287,"journal":{"name":"Frontiers in Bioscience - Elite","volume":"1 1","pages":"100258-100258"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147916845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: Nurturing Transdisciplinary Learning for Doctoral Researchers: A Doctor of Education (EdD) Programme Perspective","authors":"Timothy Fadgen, Jo Smith, Frauke Meyer","doi":"10.55578/fepr.2506.004","DOIUrl":"https://doi.org/10.55578/fepr.2506.004","url":null,"abstract":"This commentary contributes to ongoing discussions about transdisciplinary learning and collaboration in doctoral programmes. The commentary briefly considers recent research on transdiciplinarity in doctoral programme design before considering the example of a recent Doctor of Education (EdD) programme development process at an Asia-Pacific university. Amongst the reflections offered here are the importance of adopting an agile mind-set to programme design and development and the need to develop programme contingency planning to anticipate organisational changes in a precarious higher education environment. Insights from this project seek to open avenues for future research following similar doctoral programme development and implementation at universities globally.","PeriodicalId":38287,"journal":{"name":"Frontiers in Bioscience - Elite","volume":"1 1","pages":"49-52"},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nexus-press.com/journal/FEPR/article/2337/view/1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147913104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of luteolin's antibacterial mechanism against staphylococcus aureus through network pharmacology and molecular docking approaches","authors":"Shijia Lu, Tianjiao Cui, Shaofeng Wu, Yibo Wang, Hao Li, Xue Yang, Guanjie Li, Yifan Li, Huaying Du, Mengjia Yan, Jinle Wang, Xumeng Shi, Jingran Lu, Linpu Liu, Xinyang Liu, Siyu Zhang, Jinwen Sima","doi":"10.1016/j.insi.2025.100129","DOIUrl":"https://doi.org/10.1016/j.insi.2025.100129","url":null,"abstract":"This research endeavors to systematically investigate the molecular mechanisms through which luteolin exerts inhibitory effects on Staphylococcus aureus. This will be achieved by employing an integrative approach that combines network pharmacology, molecular docking, in vitro experimentation, and molecular dynamics simulation techniques. Initially, the antibacterial targets of luteolin were identified utilizing a comprehensive database, followed by the construction of a protein-protein interaction network to isolate eight key targets. Subsequently, pathway enrichment analysis, Gene Ontology (GO) biological process analysis, molecular docking, and molecular dynamics simulations were performed to elucidate the biological mechanisms through which luteolin exerts its inhibitory effects on Staphylococcus aureus. Finally, the antibacterial efficacy of luteolin against Staphylococcus aureus was evaluated. Luteolin disrupts DNA replication, energy metabolism, and cell membrane integrity by inhibiting DNA topology, ATP, and metal ion binding. In vitro tests confirmed its bactericidal effect on Staphylococcus aureus with a specific MBC/MIC ratio. This study introduces a quantitative model linking luteolin's multi-target binding energy to its concentration effect, offering a basis for developing new antibacterial agents from natural flavonoids.","PeriodicalId":38287,"journal":{"name":"Frontiers in Bioscience - Elite","volume":"1 1","pages":"100129-100129"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147890316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-genotoxic p53 reactivation via diosmin-ezetimibe-mediated MDM2 inhibition in osteosarcoma cells","authors":"Damilola A. Omoboyowa, Gagandeep Singh, Chen Ruidong, Yomiyu M. Wakjira, Yili Yang","doi":"10.1016/j.insi.2025.100116","DOIUrl":"https://doi.org/10.1016/j.insi.2025.100116","url":null,"abstract":"• Diosmin (DIO) and Ezetimibe (EZE) synergistically reduce SJSA-1 osteosarcoma cell viability (IC₅₀ = 7.0 μM). • Combination treatment induces apoptosis with minimal necrosis, showing a safer cytotoxic profile than doxorubicin (DOX). • DIO-EZE down-regulates MDM2 and moderately elevates p53, promoting non-genotoxic p53 stabilization. • Molecular docking and 100 ns MD simulations confirm stable binding of both compounds within the MDM2 pocket. • Disruption of MDM2-p53 interaction enhances p53-mediated apoptosis, suggesting a potential non-genotoxic osteosarcoma therapy. Osteosarcoma is the most common primary bone malignancy with chemotherapy resistance leading to treatment failure and severe side effects like cardiotoxicity and myelosuppression. This research explores the combined anticancer efficacy of Diosmin (DIO), a flavonoid derived from citrus, and Ezetimibe (EZE), a cholesterol absorption blocker, against SJSA-1 osteosarcoma cells, concentrating on the modulation of the MDM2-p53 pathway. Cell viability tests indicated a dose-dependent reduction in cell survival, with an IC₅₀ of 7.0 μM for the combination, nearing the cytotoxicity of doxorubicin (DOX) at elevated doses. Morphological assessments and Annexin V/PI analyses confirmed that DIO-EZE predominantly triggered apoptosis with minimal necrosis, implying a safer cytotoxic profile in comparison to DOX. Western blot and qPCR relative gene expression analysis revealed that, in contrast to DOX, which increased p53 levels without inhibiting MDM2, the combination notably decreased MDM2 expression while moderately elevating p53, suggesting p53 stabilization via non-genotoxic pathways. Molecular docking and 100 ns molecular dynamics simulations indicated that both ligands engaged in significant hydrophobic interactions within the MDM2 binding pocket and maintained stable conformations under dynamic conditions, with EZE showing the least variation. RMSF, PCA, FEL, and per-residue energy decomposition analyses supported the structural stability and favorable binding energetics of both compounds. The results imply that DIO-EZE functions synergistically by inhibiting MDM2 expression and disrupting MDM2-p53 interactions, thereby enhancing p53 stability and facilitating apoptosis. This combination presents a promising non-genotoxic approach for p53 reactivation in osteosarcoma treatment, necessitating further mechanistic validation and in vivo studies.","PeriodicalId":38287,"journal":{"name":"Frontiers in Bioscience - Elite","volume":"1 1","pages":"100116-100116"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147908325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specificity in the cAMP PKA signaling pathway differential expression regulation and subcellular localization of subunits of PKA","authors":"Bjørn Steen Skålhegg","doi":"10.2741/a543","DOIUrl":"https://doi.org/10.2741/a543","url":null,"abstract":"","PeriodicalId":38287,"journal":{"name":"Frontiers in Bioscience - Elite","volume":"5 3","pages":"d678-693"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147902602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}