Molecular Genetics and Metabolism, Год журнала: 2024, Номер 143(1-2), С. 108540 - 108540
Опубликована: Июль 17, 2024
Язык: Английский
Gut, Год журнала: 2024, Номер unknown, С. gutjnl - 332429
Опубликована: Июль 9, 2024
Objective The metabolic characteristics of liver cancer drive considerable hurdles to immune cells function and immunotherapy. However, how reprograming in the tumour microenvironment impairs antitumour response remains unclear. Design Human samples multiple murine models were employed evaluate correlation between GPR109A progression. knockout mice, depletion primary cell coculture used determine regulation on identify underlying mechanism responsible for formation intratumour + myeloid cells. Results We demonstrate that glutamine shortage drives an immunosuppressive infiltration, leading evasion surveillance. Blockade decreases G-MDSCs M2-like TAMs abundance trigger responses CD8 T further improves immunotherapy efficacy against cancer. Mechanistically, tumour-infiltrated compete uptake via transporter SLC1A5 control immunity, which disrupts endoplasmic reticulum (ER) homoeostasis induces unfolded protein promote expression through IRE1α/XBP1 pathway. restriction cells, as well blockade signalling or supplementation, can eliminate effects slow down Conclusion Our findings immunometabolic crosstalk facilitates progression a metabolism/ER stress/GPR109A axis, suggesting be exploited checkpoint putative target treatment.
Язык: Английский
Процитировано
12
Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102480 - 102480
Опубликована: Сен. 3, 2024
Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.
Язык: Английский
Процитировано
11
Sensors and Actuators Reports, Год журнала: 2025, Номер unknown, С. 100303 - 100303
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
1
Cellular Signalling, Год журнала: 2024, Номер 124, С. 111462 - 111462
Опубликована: Окт. 10, 2024
Язык: Английский
Процитировано
7
Molecular Biomedicine, Год журнала: 2024, Номер 5(1)
Опубликована: Ноя. 29, 2024
Abstract Tumor energy metabolism plays a crucial role in the occurrence, progression, and drug resistance of tumors. The study tumor has gradually become an emerging field treatment. Recent studies have shown that epigenetic regulation is closely linked to metabolism, influencing metabolic remodeling biological traits cells. This review focuses on primary pathways explores therapeutic strategies target these pathways. It covers key areas such as glycolysis, Warburg effect, mitochondrial function, oxidative phosphorylation, adaptability Additionally, this article examines regulator SWI/SNF complex specifically its interactions with glucose, lipids, amino acids. Summarizing aimed at pathways, including inhibitors mitochondrial-targeted drugs, exploitation vulnerabilities, recent developments related complexes potential targets. clinical significance, challenges, future directions research are discussed, overcome resistance, combination therapy, application new technologies.
Язык: Английский
Процитировано
6
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 17, 2025
Lactate metabolism (LM) plays a crucial role in tumor progression and therapy resistance non-small cell lung cancer (NSCLC). Several methods had been developed for NSCLC prognosis prediction based on lactate metabolism-related information. The existing the construction of models are mostly single such as linear models, SVM, decision trees. Prognosis biomarkers this kind often have limited prognostic performance. In study, we proposed novel methodology constructing model identifying lactate-related NSCLC. We first screened malignant genes from scRNA-Seq data cells. Cox elastic-net regression combined with genetic algorithm (GA-EnCox) to predict optimize selection key biomarkers. identified five LM-related (LYPD3, KRT8, CCT6A, PSMB7, HMGA1) that significantly correlated patient LUAD cohorts. constructed these outperformed other currently popular across multiple datasets, demonstrating stable predictive capability. Survival analysis bulk RNA-Seq demonstrated low-risk group better overall survival compared high-risk group. Further revealed risk might be associated monocyte lineages macrophages DC's infiltration may indicate therapeutic responses immune checkpoint inhibitors patients. More importantly, validated HMGA1 KRT8 at protein level their association histologic grades, stages, clinical outcomes consistently treated in-house Finally, experimentally one biomarkers, HMGA1, confirming its promoting phenotypes This study provides valuable insights into impact outcomes, it was expected provide important reference value assessment personalized treatment
Язык: Английский
Процитировано
0
MedComm – Oncology, Год журнала: 2025, Номер 4(1)
Опубликована: Фев. 17, 2025
ABSTRACT Metastasis remains a leading cause of cancer‐related deaths, defined by complex, multi‐step process in which tumor cells spread and form secondary growths distant tissues. Despite substantial progress understanding metastasis, the molecular mechanisms driving this development effective therapies remain incompletely understood. Elucidating pathways governing metastasis is essential for discovery innovative therapeutic targets. The rapid advancements sequencing technologies expansion biological databases have significantly deepened our drivers associated drug resistance. This review focuses on particularly roles genetic mutations, epigenetic changes, post‐translational modifications progression. We also examine how microenvironment influences metastatic behavior explore emerging strategies, including targeted immunotherapies. Finally, we discuss future research directions, stressing importance novel treatment approaches personalized strategies to overcome improve patient outcomes. By integrating contemporary insights into basis innovation, provides comprehensive framework guide clinical cancer.
Язык: Английский
Процитировано
0
Phytomedicine, Год журнала: 2025, Номер 140, С. 156562 - 156562
Опубликована: Фев. 25, 2025
Язык: Английский
Процитировано
0
Frontiers in Oncology, Год журнала: 2025, Номер 15
Опубликована: Март 4, 2025
Ovarian cancer, known for its high invasiveness and therapeutic resistance, is one of the leading causes death from gynecological tumors. The tumor microenvironment (TME) plays a crucial role in development ovarian with cancer-associated fibroblasts (CAFs) being key non-tumor cell component. They significantly affect prognosis cancer by promoting proliferation, invasion, metastasis, immune evasion, drug resistance. heterogeneity CAFs provides new perspective targeted therapy cancer. This review comprehensively analyzes mechanisms action, characteristics, discusses strategies CAFs, aiming to provide theoretical basis treatment directions
Язык: Английский
Процитировано
0
Experimental Hematology and Oncology, Год журнала: 2025, Номер 14(1)
Опубликована: Март 8, 2025
Cancer remains the leading cause of mortality worldwide, and emergence drug resistance has made identification new therapeutic targets imperative. Lactate, traditionally viewed as a byproduct glycolysis with limited ATP-producing capacity, recently gained recognition critical signaling molecule. It plays key role not only in cancer cell metabolism but also shaping tumor microenvironment (TME). Histone lysine lactylation, newly identified post-translational modification, been shown to influence range cellular processes cancer. Current research focuses on mechanisms functions histone lactylation cancer, including its gene expression regulation, signal transduction, protein synthesis. However, despite these advancements, there are still plenty barriers quest unravel modification. The single-cell spatial transcriptomics may offer valuable insights for selecting targets. This review provides comprehensive summary applications modification clinical settings. Through detailed analysis, we identify challenges limitations that exist current landscape. These lay groundwork future studies by highlighting promising directions.
Язык: Английский
Процитировано
0