Ask about this productRelated genes to: PURA antibody
- Gene:
- PURA NIH gene
- Name:
- purine rich element binding protein A
- Previous symbol:
- -
- Synonyms:
- PURALPHA, PUR1, PUR-ALPHA
- Chromosome:
- 5q31.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-10-19
- Date modifiied:
- 2017-09-22
Related products to: PURA antibody
Related articles to: PURA antibody
- Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that directly interface with epigenetic machinery. These TME-activated pathways recruit DNA methyltransferases, histone-modifying enzymes, and regulate microRNA (miRNA) networks, establishing stable resistant phenotypes including epithelial-mesenchymal transition, cancer stem cells, and metabolic adaptation. Critically, miRNA dysregulation serves as a central integrator, creating bidirectional crosstalk between signaling pathways and epigenetic modifications through self-reinforcing circuits. Unlike previous reviews focusing on isolated resistance mechanisms, we demonstrate how this integrated TME-epigenetic axis creates specific therapeutic vulnerabilities exploitable through rationally designed nanotechnology platforms delivering epigenetic modulators (DNMT inhibitors, HDAC inhibitors, EZH2 inhibitors) and gene therapy tools (CRISPR-Cas9 epigenetic editors, miRNA mimics/antagomirs). We critically evaluate clinical translation challenges, including EPR effect heterogeneity, delivery barriers, and biomarker gaps, providing a balanced perspective on both potential and obstacles. This mechanistic framework guides the development of next-generation combination therapies targeting multiple nodes within the TME-epigenetic-nanotherapy axis. - Source: PubMed
Publication date: 2026/05/04
Sharma PrashantThuy Nguyen PhuongAnsari Israrul HTripathi Ravi ManiKala MrinaliniElberry Mostafa HSharma NeeleshLee Sung-Jin - Central carbon metabolism is thought to link reactive oxygen species (ROS) with antibiotic-mediated bacterial death. During enrichment screening of with the first-generation quinolone oxolinic acid, unstable antibiotic-tolerant mutants containing deficiencies in were obtained. Examination of a stable deletion mutant of , a gene functionally related to , revealed reduced lethality of oxolinic acid and ciprofloxacin. This deletion mutation had little effect on the minimal inhibitory concentration (MIC) of quinolones, thereby demonstrating that the observed protection from killing was attributable to antibiotic tolerance. AMP synthesis was blocked by the Δ mutation, and ciprofloxacin tolerance was reversed by exogenous AMP supplementation. Because AMP is a precursor of ATP, interference with ATP synthesis occurs in the Δ mutant. RNA-Seq analysis showed that, prior to antibiotic stress, transcript levels of NADH:quinone oxidoreductase genes were reduced by the deficiency, thereby predisposing to antibiotic tolerance through reduced respiration. During ciprofloxacin exposure, the deficiency also suppressed the surge in expression of tricarboxylic acid (TCA) cycle and ATP synthesis genes, as well as the accumulation of intracellular ATP and ROS. Thus, wild-type PurA, and by extension the downstream enzyme PurB, directs AMP toward an antibiotic-mediated, ROS-dependent death pathway. Overall, defects in PurA/PurB-mediated adenosine ribonucleotides biosynthesis reveal a novel quinolone tolerance mechanism that is initiated outside central carbon metabolism; tolerance is likely attributable to a limited supply of AMP, resulting in reduced ATP synthesis and suppression of ROS accumulation. - Source: PubMed
Publication date: 2026/04/16
Zhu WeiweiNong YuejuanSu JieYang JingwenMa LinaXue YunxinWang DaiNiu JianjunDrlica KarlZhao Xilin - - Source: PubMed
Portella Tatiana PPicinini Freitas LaísResende Paola Cristinada Costa Gomes Marcelo FerreiraBastos Leonardo S - Community-associated methicillin-resistant (CA-MRSA) is a leading cause of bacteremia, yet the genetic basis for its success in this hostile environment remains poorly defined. In this study, we employed transposon-directed insertion site sequencing (TraDIS) to map the fitness landscape of CA-MRSA strain USA300 JE2 through a genome-wide screening in fresh, immunocompetent human blood. We identified 76 genes required for fitness, including genes involved in respiratory and central carbon metabolisms, heme detoxification, and purine biosynthesis. As validation of fitness genes, competition assays confirmed that individual disruption of , , , , or significantly reduced bacterial fitness in blood. Conversely, inactivation of specific regulators, such as the two-component system, the alternative sigma factor σ, and adhesins, including and , conferred a competitive advantage. These findings provide a genome-scale map of fitness requirements in a physiologically relevant blood model, offering a platform for further investigation of bacterial adaptation to the intravascular environment.IMPORTANCEUnderstanding how maintains fitness in the human bloodstream is essential for explaining its success as an invasive pathogen. This study provides a comprehensive, genome-wide definition of the genes that enable to remain competitive in blood, revealing the key physiological requirements for adaptation to this challenging environment. By identifying genetic functions whose disruption impairs fitness, our findings highlight the specific pathways that sustain adaptation and competitiveness under host-imposed stress. Extending previous genome-scale investigations conducted in other infection niches, this study emphasizes the importance of physiological context in shaping bacterial fitness and identifies conserved cross-fitness determinants shared among lineages. These insights advance our current understanding of how adapts to the bloodstream and strengthen the foundation for future functional and comparative studies on staphylococcal pathophysiology. - Source: PubMed
Publication date: 2026/04/21
Abdelmalek NaderYousief Sally WBojer Martin SOlsen John ERubino SalvatorePaglietti Bianca - In this paper, we develop a connectivity-exact bond-resolved framework for quantifying structural accessibility and persistence in drug molecules. Representing a molecule as a heavy-atom graph [Formula: see text] each bond is classified uniquely as either a connectivity-critical Entry-point bond ([Formula: see text]) or a connectivity-preserving Fortress bond ([Formula: see text]) yielding the exact identity [Formula: see text] This exhaustive partition separates fragmentation capacity from invariant scaffold structure without adjustable parameters. To refine the invariance coordinate we introduce Total Structural Entrenchment (TSE) a persistence-weighted functional defined over cycle-supported bonds and modulated by local steric wall contributions [Formula: see text]. The resulting two-parameter embedding [Formula: see text] distinguishes superficial cyclic extent from deeply embedded structural reinforcement and resolves degeneracies inherent in raw bond counts. Metabolic progression is formalized as recursive bridge depletion generating a directed migration across the architectural plane toward a bridge-depleted refractory core. Within this framework scaffold persistence is interpreted as a connectivity-driven contraction governed strictly by graph topology. The resulting invariance-variation embedding establishes a mathematically controlled bond-level representation of structural accessibility and cyclic entrenchment. - Source: PubMed
Devi K NaliniSrinivasa G