Glioblastoma(GBM)remains the most aggressive and lethal brain tumor in adults and poses significant challenges to patient survival.This review provides a comprehensive exploration of the molecular and genetic landscap...Glioblastoma(GBM)remains the most aggressive and lethal brain tumor in adults and poses significant challenges to patient survival.This review provides a comprehensive exploration of the molecular and genetic landscape of GBM,focusing on key oncogenic drivers,such as epidermal growth factor receptor(EGFR),platelet-derived growth factor receptor(PDGFR),and the PI3K/AKT/mTOR pathway,which are critical for tumorigenesis and progression.We delve into the role of epigenetic alterations,including DNA methylation and histone modifications,in driving therapy resistance and tumor evolution.The tumor microenvironment is known for its pivotal role in immune evasion,with tumor-associated macrophages,myeloid-derived suppressor cells,and regulatory T cells creating an immunosuppressive niche that sustains GBM growth.Emerging therapies,such as immunotherapies,oncolytic viral therapies,extracellular vesicle-based approaches,and non-coding RNA interventions,are highlighted as promising avenues to disrupt GBM pathogenesis.Advances in precision medicine and innovative technologies,including electric field therapy and locoregional treatments,are discussed for their potential to overcome the blood‒brain barrier and treatment resistance.Additionally,this review underscores the importance of metabolic reprogramming,particularly hypoxia-driven adaptations and altered lipid metabolism,in fueling GBM progression and influencing the therapeutic response.展开更多
Vitamin B_(2)is an essential water-soluble vitamin.For most prokaryotes,a bifunctional enzyme called FAD synthase catalyzes the successive conversion of riboflavin to FMN and FAD.In this study,the plasmid pNEW-AZ cont...Vitamin B_(2)is an essential water-soluble vitamin.For most prokaryotes,a bifunctional enzyme called FAD synthase catalyzes the successive conversion of riboflavin to FMN and FAD.In this study,the plasmid pNEW-AZ containing six key genes for the riboflavin synthesis was transformed into strain R2 with the deleted FMN riboswitch,yielding strain R5.The R5 strain could produce 540.23±5.40 mg/L riboflavin,which was 10.61%higher than the R4 strain containing plasmids pET-AE and pAC-Z harboring six key genes.To further enhance the production of riboflavin,homology matching and molecular docking were performed to identify key amino acid residues of FAD synthase.Nine point mutation sites were identified.By comparing riboflavin kinase activity,mutations of T203D and N210D,which respectively decreased by 29.90%and 89.32%compared to wild-type FAD synthase,were selected for CRISPR/Cas9 gene editing of the genome,generating engineered strains R203 and R210.pNEW-AZ was transformed into R203,generating R6.R6 produced 657.38±47.48 mg/L riboflavin,a 21.69%increase compared to R5.This study contributes to the high production of riboflavin in recombinant E.coli BL21.展开更多
文摘Glioblastoma(GBM)remains the most aggressive and lethal brain tumor in adults and poses significant challenges to patient survival.This review provides a comprehensive exploration of the molecular and genetic landscape of GBM,focusing on key oncogenic drivers,such as epidermal growth factor receptor(EGFR),platelet-derived growth factor receptor(PDGFR),and the PI3K/AKT/mTOR pathway,which are critical for tumorigenesis and progression.We delve into the role of epigenetic alterations,including DNA methylation and histone modifications,in driving therapy resistance and tumor evolution.The tumor microenvironment is known for its pivotal role in immune evasion,with tumor-associated macrophages,myeloid-derived suppressor cells,and regulatory T cells creating an immunosuppressive niche that sustains GBM growth.Emerging therapies,such as immunotherapies,oncolytic viral therapies,extracellular vesicle-based approaches,and non-coding RNA interventions,are highlighted as promising avenues to disrupt GBM pathogenesis.Advances in precision medicine and innovative technologies,including electric field therapy and locoregional treatments,are discussed for their potential to overcome the blood‒brain barrier and treatment resistance.Additionally,this review underscores the importance of metabolic reprogramming,particularly hypoxia-driven adaptations and altered lipid metabolism,in fueling GBM progression and influencing the therapeutic response.
基金the Natural Science Foundation of Zhejiang Province,China(No.LY21C200006)。
文摘Vitamin B_(2)is an essential water-soluble vitamin.For most prokaryotes,a bifunctional enzyme called FAD synthase catalyzes the successive conversion of riboflavin to FMN and FAD.In this study,the plasmid pNEW-AZ containing six key genes for the riboflavin synthesis was transformed into strain R2 with the deleted FMN riboswitch,yielding strain R5.The R5 strain could produce 540.23±5.40 mg/L riboflavin,which was 10.61%higher than the R4 strain containing plasmids pET-AE and pAC-Z harboring six key genes.To further enhance the production of riboflavin,homology matching and molecular docking were performed to identify key amino acid residues of FAD synthase.Nine point mutation sites were identified.By comparing riboflavin kinase activity,mutations of T203D and N210D,which respectively decreased by 29.90%and 89.32%compared to wild-type FAD synthase,were selected for CRISPR/Cas9 gene editing of the genome,generating engineered strains R203 and R210.pNEW-AZ was transformed into R203,generating R6.R6 produced 657.38±47.48 mg/L riboflavin,a 21.69%increase compared to R5.This study contributes to the high production of riboflavin in recombinant E.coli BL21.
