ROS-regulated SUR1-TRPM4 drives persistent activation of NLRP3 inflammasome in microglia after whole-brain radiation DOI Creative Commons
Yuan Chang,

Yihua He,

Di Wang

и другие.

Acta Neuropathologica Communications, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 27, 2025

Delayed radiation-induced brain injury (RIBI) characterized by progressive cognitive decline significantly impacts patient outcomes after radiotherapy. The activation of NLRP3 inflammasome within microglia radiation is involved in the progression RIBI mediating inflammatory responses. We have previously shown that sulfonylurea receptor 1-transient potential M4 (SUR1-TRPM4) mediates microglial NLRP3-related inflammation following global ischemia. However, role SUR1-TRPM4 remains unclear. Here, we found whole-brain induced up-regulation and assembly SUR1-TRPM4, which further activated caused persistent neuroinflammation mice. Blocking glibenclamide or gene deletion Trpm4 effectively prevented NLRP3-mediated alleviated RIBI. Utilizing mouse model irradiated BV2 cells, demonstrated irradiation mitochondrial damage to microglia, leading violent release reactive oxygen species (ROS), enhanced transcription SUR1, TRPM4, inflammasome-related molecules. Moreover, ROS up-regulated ten-eleven translocation 2 (TET2) enhance TRPM4 expression demethylation promoter, thereby facilitating microglia. In summary, this study deciphers crucially under action radiation, offering novel therapeutic strategies for delayed as well other neurological disorders involving excessive production.

Язык: Английский

TET Enzymes in the Immune System: From DNA Demethylation to Immunotherapy, Inflammation, and Cancer DOI
Isaac F. López-Moyado, Myunggon Ko, Patrick G. Hogan

и другие.

Annual Review of Immunology, Год журнала: 2024, Номер 42(1), С. 455 - 488

Опубликована: Фев. 16, 2024

Ten-eleven translocation (TET) proteins are iron-dependent and α-ketoglutarate-dependent dioxygenases that sequentially oxidize the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) 5-carboxylcytosine (5caC). All three epigenetic modifications intermediates in DNA demethylation. TET recruited by transcription factors RNA polymerase II modify 5mC at enhancers gene bodies, thereby regulating expression during development, cell lineage specification, activation. It is not yet clear, however, how established biochemical activities enzymes oxidizing mediating demethylation relate known association deficiency with inflammation, clonal hematopoiesis, cancer. There hints ability promote proliferation a signal-dependent manner may be harnessed for cancer immunotherapy. In this review, we draw upon recent findings cells immune system illustrate as well emerging ideas influence cellular function.

Язык: Английский

Процитировано

26
The interaction between DNA methylation and tumor immune microenvironment: from the laboratory to clinical applications DOI Creative Commons
Daoqi Zhu, Siying Zeng, Chao Su

и другие.

Clinical Epigenetics, Год журнала: 2024, Номер 16(1)

Опубликована: Фев. 8, 2024

Abstract DNA methylation is a pivotal epigenetic modification that affects gene expression. Tumor immune microenvironment (TIME) comprises diverse cells and stromal components, creating complex landscape can either promote or inhibit tumor progression. In the TIME, has been shown to play critical role in influencing cell function evasion. regulates differentiation, responses, TIME composition Targeting offers various potential avenues for enhancing cytotoxicity reducing immunosuppression. Recent studies have demonstrated of patterns infiltration function. However, challenges persist understanding precise mechanisms underlying developing selective therapies, effectively integrating these therapies with other antitumor strategies. conclusion, both interacts thus clinical efficacy. The regulation within holds significant promise advancement immunotherapy. Addressing crucial harnessing full interventions enhance responses improve patient outcomes.

Язык: Английский

Процитировано

20
Cancer Epigenetics: An Overview DOI Open Access
Félix Recillas‐Targa

Archives of Medical Research, Год журнала: 2022, Номер 53(8), С. 732 - 740

Опубликована: Ноя. 18, 2022

Язык: Английский

Процитировано

65
Redox signaling in drug-tolerant persister cells as an emerging therapeutic target DOI Creative Commons
Zhe Zhang,

Yunhan Tan,

Canhua Huang

и другие.

EBioMedicine, Год журнала: 2023, Номер 89, С. 104483 - 104483

Опубликована: Фев. 22, 2023

Язык: Английский

Процитировано

38
NF-κB and TET2 promote macrophage reprogramming in hypoxia that overrides the immunosuppressive effects of the tumor microenvironment DOI Creative Commons
Carlos de la Calle‐Fabregat, Josep M. Calafell, Margaux Gardet

и другие.

Science Advances, Год журнала: 2024, Номер 10(38)

Опубликована: Сен. 18, 2024

Macrophages orchestrate tissue homeostasis and immunity. In the tumor microenvironment (TME), macrophage presence is largely associated with poor prognosis because of their reprogramming into immunosuppressive cells. We investigated effects hypoxia, a TME-associated feature, on functional, epigenetic, transcriptional macrophages found that hypoxia boosts immunogenicity. Hypoxic inflammatory are characterized by cluster proinflammatory genes undergoing ten-eleven translocation–mediated DNA demethylation overexpression. These regulated NF-κB, while HIF1α dominates reprogramming, demonstrated through ChIP-seq pharmacological inhibition. bladder ovarian carcinomas, hypoxic enriched in immune-infiltrated tumors, correlating better patient prognoses. Coculture assays cell-cell communication analyses support hypoxic-activated enhance T cell–mediated responses. The NF-κB–associated hypomethylation signature displayed subset macrophages, isolated from tumors. Our results challenge paradigms regarding highlight actionable target cells to modulate anticancer immune

Язык: Английский

Процитировано

9
Genome-wide pan-GPCR cell libraries accelerate drug discovery DOI Creative Commons
Hanting Yang, Yongfu Wang, Wei Liu

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(10), С. 4296 - 4311

Опубликована: Июнь 26, 2024

G protein-coupled receptors (GPCRs) are pivotal in mediating diverse physiological and pathological processes, rendering them promising targets for drug discovery. GPCRs account about 40% of FDA-approved drugs, representing the most successful targets. However, only approximately 15% 800 human targeted by market leaving numerous opportunities discovery among remaining receptors. Cell expression systems play crucial roles GPCR field, including novel target identification, structural functional characterization, potential ligand screening, signal pathway elucidation, safety evaluation. Here, we discuss principles, applications, limitations widely used cell GPCR-targeted discovery, function investigation, pharmacological property studies. We also propose three strategies constructing genome-wide pan-GPCR libraries, which will provide a powerful platform facilitate study mechanisms evaluation, ultimately accelerating process

Язык: Английский

Процитировано

8
Differences between lung adenocarcinoma and lung squamous cell carcinoma: Driver genes, therapeutic targets, and clinical efficacy DOI Creative Commons
Yue Shen,

Jie-Qi Chen,

Xiangping Li

и другие.

Genes & Diseases, Год журнала: 2024, Номер 12(3), С. 101374 - 101374

Опубликована: Июль 11, 2024

With the rapid advancements in second-generation gene sequencing technologies, a growing number of driver genes and associated therapeutic targets have been unveiled for lung adenocarcinoma (LUAD) squamous cell carcinoma (LUSC). While they are clinically classified as non-small cancer (NSCLC), display distinct genomic features substantial variations clinical efficacy, underscoring need particular attention. Hence, this review provides comprehensive overview latest genes, epigenetic targets, chemotherapy, targeted therapy, immunotherapy LUAD LUSC. Additionally, it delves into distinctions signaling pathways pivotal facets management specific to these two categories cancer. Moreover, we furnish pertinent details regarding trials pertaining epigenetics, thus establishing theoretical foundation realization precision treatments

Язык: Английский

Процитировано

8
Epigenetic regulation of human FOXP3+ Tregs: from homeostasis maintenance to pathogen defense DOI Creative Commons

Yi Yue,

Yuqing Ren,

Chunya Lu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 31, 2024

Regulatory T cells (Tregs), characterized by the expression of Forkhead Box P3 (FOXP3), constitute a distinct subset crucial for immune regulation. Tregs can exert direct and indirect control over homeostasis releasing inhibitory factors or differentiating into Th-like Treg (Th-Treg), thereby actively contributing to prevention treatment autoimmune diseases. The epigenetic regulation

Язык: Английский

Процитировано

7
TET1: The epigenetic architect of clinical disease progression DOI Creative Commons

Keyvan Jabbari,

Ali Khalafizadeh,

Mahboubeh Sheikhbahaei

и другие.

Genes & Diseases, Год журнала: 2025, Номер unknown, С. 101513 - 101513

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Unveiling the future of cancer stem cell therapy: a narrative exploration of emerging innovations DOI Creative Commons

Joseph Nhyira Obisi,

Abike Ndidiamaka Josephine Abimbola,

Oluwasegun Adesina Babaleye

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Март 22, 2025

Cancer stem cells (CSCs), are a critical subpopulation within tumours, and defined by their capacity for self-renewal, differentiation, tumour initiation. These unique traits contribute to progression, metastasis, resistance conventional treatments like chemotherapy radiotherapy, often resulting in cancer recurrence poor patient outcomes. As such, CSCs have become focal points developing advanced therapies. This review highlights progress CSC-targeted treatments, including chimeric antigen receptor T-cell (CAR-T) therapy, immunotherapy, molecular targeting, nanoparticle-based drug delivery systems. Plant-derived compounds gene-editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR), explored potential enhance precision minimize side effects. Metabolic pathways integral CSC survival, mitochondrial dynamics, mitophagy (regulated dynamin-related protein 1 [DRP1] the PINK1/Parkin pathway), one-carbon metabolism, amino acid metabolism (involving enzymes glutaminase (GLS) glutamate dehydrogenase (GDH]), lipid hypoxia-induced metabolic reprogramming mediated hypoxia-inducible factors (HIF-1α HIF-2α), examined therapeutic targets. The adaptability of through autophagy, flexibility, epigenetic regulation metabolites α-ketoglutarate, succinate, fumarate is discussed. Additionally, extracellular vesicles nicotinamide adenine dinucleotide (NAD⁺) identified pivotal redox balance, DNA repair, modifications. Addressing challenges heterogeneity, immune evasion, treatment durability requires interdisciplinary collaboration. Advancing therapies essential overcoming preventing relapse, paving way transformative treatments. underscores importance leveraging innovative technologies fostering collaboration revolutionize treatment.

Язык: Английский

Процитировано

1