Trends in Microbiology, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 1, 2024
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: March 7, 2025
Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.
Language: Английский
Citations
3
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 18, 2025
Epitranscriptomic modifications, particularly N6-methyladenosine (m6A), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting m6A from Nanopore direct sequencing (DRS) data constrained by their reliance on experimentally validated labels, often resulting in the underestimation modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive unlabeled multi-instance learning (MIL) to address challenges incomplete labeling missing read-level annotations. By combining electrical signal features with base alignment employing a weighted Noisy-OR probability mechanism, pum6a achieves enhanced sensitivity accuracy detection, low-coverage loci. Pum6a outperforms existing identifying sites across various cell lines species, without requiring extensive parameter tuning. We further apply study dynamic regulation demethylases gastric cancer under hypoxia, revealing distinct roles FTO ALKBH5 modulating modifications uncovering key insights into -mediated transcript stability. Our findings highlight potential powerful tool advancing understanding epitranscriptomic health disease, paving way biotechnological therapeutic applications.
Language: Английский
Citations
1
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116559 - 116559
Published: April 10, 2024
Breast cancer comprises a substantial proportion of diagnoses in women and is primary cause cancer-related mortality. While hormone-responsive cases generally have favorable prognosis, the aggressive nature triple-negative breast presents challenges, with intrinsic resistance to established treatments being persistent issue. The complexity intensifies emergence acquired resistance, further complicating management cancer. Epigenetic changes, encompassing DNA methylation, histone RNA modifications, non-coding RNAs, are acknowledged as crucial contributors heterogeneity unique epigenetic landscape harbored by each cellular component within tumor microenvironment (TME) adds great diversity intricate regulations which influence therapeutic responses. TME, sophisticated ecosystem non-cellular elements interacting cells, establishes an immunosuppressive fuels processes such growth, angiogenesis, extracellular matrix remodeling. These factors contribute challenging conditions treatment fostering hypoxic environment, inducing metabolic stress, creating physical barriers drug delivery. This article delves into complex connections between response, underlying vital interactions TME. To restore sensitivity treatment, it emphasizes need for combination therapies considering changes specific individual members Recognizing pivotal role epigenetics comprehending specificities TME essential devising more effective strategies. development reliable biomarkers patient stratification will facilitate tailored precise approaches.
Language: Английский
Citations
7
Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14
Published: Jan. 7, 2025
Cancer's epigenetic landscape, a labyrinthine tapestry of molecular modifications, has long captivated researchers with its profound influence on gene expression and cellular fate. This review discusses the intricate mechanisms underlying cancer epigenetics, unraveling complex interplay between DNA methylation, histone chromatin remodeling, non-coding RNAs. We navigate through tumultuous seas dysregulation, exploring how these processes conspire to silence tumor suppressors unleash oncogenic potential. The narrative pivots cutting-edge technologies, revolutionizing our ability decode epigenome. From granular insights single-cell epigenomics holistic view offered by multi-omics approaches, we examine tools are reshaping understanding heterogeneity evolution. also highlights emerging techniques, such as spatial long-read sequencing, which promise unveil hidden dimensions regulation. Finally, probed transformative potential CRISPR-based epigenome editing computational analysis transmute raw data into biological insights. study seeks synthesize comprehensive yet nuanced contemporary landscape future directions research.
Language: Английский
Citations
0
Results in Engineering, Journal Year: 2025, Volume and Issue: unknown, P. 104238 - 104238
Published: Feb. 1, 2025
Language: Английский
Citations
0
Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 207 - 207
Published: Feb. 3, 2025
Breast cancer is the most common malignancy affecting women, manifesting as a heterogeneous disease with diverse molecular characteristics and clinical presentations. Recent studies have elucidated role of epigenetic modifications in pathogenesis breast cancer, including drug resistance efflux characteristics, offering potential new diagnostic prognostic markers, treatment efficacy predictors, therapeutic agents. Key include DNA cytosine methylation covalent modification histone proteins. Unlike genetic mutations, reprogramming landscape epigenome promising targeted therapy for reversal resistance. Epidrugs, which target modifications, can provide novel options by reversing acquired to treatment. Currently, approach involves combination therapies consisting epidrugs immune checkpoint inhibitors. This review examines aberrant regulation initiation progression, focusing on related estrogen signaling, resistance, epithelial–mesenchymal transition (EMT). It existing drugs treating agents that modify DNA, inhibitors acetyltransferases, deacetylases, methyltransferases, demethyltransferases. also delves into ongoing combining other addresses upcoming obstacles this field.
Language: Английский
Citations
0
Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Language: Английский
Citations
0
Epigenomes, Journal Year: 2025, Volume and Issue: 9(1), P. 6 - 6
Published: Feb. 11, 2025
Aberrant hypermethylation in the promoter regions of tumor suppressor genes facilitates pathogenesis and progression cancer. Therefore, inhibitors targeting DNA methyltransferase (DNMT) have been tested clinical studies. However, current monotherapy DNMT shows limited efficacy. Furthermore, mechanism action is replication-dependent. To address these limitations, we developed a novel core-shell-type "epigenetics control (EpC) nanocarrier" that encapsulated decitabine (5-aza-dC) PLGA core nanoparticle hybridized TET1 gene-encoding pDNA on lipid shell surface. This study aimed to evaluate whether dual delivery could synergistically enhance gene expression induce cell cycle arrest and/or apoptosis cancer cells. Herein, demonstrate potential EpC carrier HCT116 human colon cells upregulate rapidly achieve arrest. nanoparticles were prepared by W/O/W double emulsion method. The formation core-shell complexation with investigated optimized dynamic light scattering, zeta measurement, agarose gel electrophoresis. cellular uptake transfection efficiency measured confocal laser scanning microscopy luciferase assay, respectively. p53 protein was detected Western blotting. anti-tumor effects nanocarrier evaluated analysis an assay. delivered inhibitor TET into It promoted induced rapid G2/M phase Our findings suggest dual-targeting enzymes effectively repairs aberrant methylation induces growth cells, strategy may contribute advancement epigenetic therapy.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3225 - 3225
Published: March 30, 2025
Although periodontal disease (PD) is reported to be associated with changes in various genes and proteins both invading bacteria the host, its molecular mechanism of pathogenesis remains unclear. Changes immune inflammatory play a significant role PD pathogenesis. Some reports relate alterations cellular epigenetic patterns characteristics, while several high-throughput analyses indicate thousands differentially methylated patients controls. Furthermore, DNA methylation inflammation-related have been linked efficacy therapy, as demonstrated by findings related cytochrome C oxidase II gene. Distinct mesenchymal stem cells from controls persisted despite reversal phenotypic PD. Methyl groups for are supplied S-adenosylmethionine, which synthesized involvement folate, an essential nutrient known maintaining mitochondrial homeostasis, compromised Folate may benefit through antioxidant action against reactive oxygen nitrogen species that overproduced dysfunctional mitochondria. As such, methylation, dietary quality control interact In this narrative/hypothesis review, we demonstrate how may, turn, improved potentially altering nucleus Therefore, folate-based intervention recommended prevention adjunct therapy. At same time, further research needed on mechanisms beneficial effects folate studies.
Language: Английский
Citations
0
Inside Precision Medicine, Journal Year: 2025, Volume and Issue: 12(2), P. 22 - 24, 26, 27, 28
Published: April 1, 2025
Language: Английский
Citations
0