The impact of glucose metabolism on inflammatory processes in sepsis-induced acute lung injury DOI Creative Commons

Shilei Cheng,

Yufei Li, Xiaoliang Sun

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 6, 2024

Acute lung injury (ALI) is a prevalent and critical complication of sepsis, marked by high incidence mortality rates, with its pathogenesis still not being fully elucidated. Recent research has revealed significant correlation between the metabolic reprogramming glucose sepsis-associated ALI (S-ALI). Throughout course S-ALI, immune cells, including macrophages dendritic undergo shifts to accommodate intricate demands function that emerge as sepsis advances. Indeed, in S-ALI serves double-edged sword, fueling inflammatory responses initial stages subsequently initiating anti-inflammatory disease evolves. In this review, we delineate current progress concerning pathogenic mechanisms linked focus on pertinent cells implicated. We encapsulate impact onset, progression, prognosis S-ALI. Ultimately, examining key regulatory factors within intermediates enzymes, have identified potential therapeutic targets reprogramming, striving tackle inherent challenges diagnosing treating Severe Lung Injury (S-ALI) greater efficacy.

Language: Английский

Emerging roles of lactate in acute and chronic inflammation DOI Creative Commons

Yunda Fang,

Zhengjun Li, Lili Yang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 16, 2024

Abstract Traditionally, lactate has been considered a ‘waste product’ of cellular metabolism. Recent findings have shown that is substance plays an indispensable role in various physiological functions and contributes to energy metabolism signal transduction during immune inflammatory responses. The discovery lactylation further revealed the regulating processes. In this review, we comprehensively summarize paradoxical characteristics microenvironment highlight pivotal roles homeostasis, shuttle, (‘lactate clock’) acute chronic responses from molecular perspective. We especially focused on receptors with either proinflammatory or anti-inflammatory effects complex biological signalling pathways investigated dynamic changes cells lactate-related microenvironment. Moreover, reviewed progress use as therapeutic target for response, which may provide new perspective treating inflammation-related diseases.

Language: Английский

Citations

28
Lactate and lactylation: Behind the development of tumors DOI

Enci Dai,

Wei Wang, Yingying Li

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216896 - 216896

Published: April 17, 2024

Language: Английский

Citations

26
LKB1 inhibits telomerase activity resulting in cellular senescence through histone lactylation in lung adenocarcinoma DOI Creative Commons
Mingdi Liu,

Liting Gu,

Yuning Zhang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 595, P. 217025 - 217025

Published: June 5, 2024

Despite the confirmed role of LKB1 in suppressing lung cancer progression, its precise effect on cellular senescence is unknown. The aim this research was to clarify and mechanism restraining telomerase activity adenocarcinoma. results showed that induced apoptosis either vitro or vivo. Overexpression LKB1-deficient A549 cells led inhibition induction telomere dysfunction by regulating reverse transcriptase (TERT) expression terms transcription. As a transcription factor, Sp1 mediated TERT after overexpression. lactate production inhibited histone H4 (Lys8) (Lys16) lactylation, which further altered Sp1-related transcriptional activity. inhibitor BIBR1532 beneficial for achieving optimum curative traditional chemotherapeutic drugs accompanied glycolysis 2DG. These data reveal new regulates through lactylation-dependent inhibition, therefore, provide insights into effects LKB1-mediated Our has opened up possibilities creation treatments.

Language: Английский

Citations

10
Regulation of macrophage activation by lactylation in lung disease DOI Creative Commons
Yungeng Wei, Hua Guo,

Shixing Chen

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Lactylation is a process where lactate, cellular metabolism byproduct, added to proteins, altering their functions. In the realm of macrophage activation, lactylation impacts inflammatory response and immune regulation. Understanding effects on activation vital in lung diseases, as abnormal function are pivotal conditions like pneumonia, pulmonary fibrosis, COPD, cancer. This review explores concept lactylation, its regulation recent research progress diseases. It offers new insights into disease pathogenesis potential therapeutic targets.

Language: Английский

Citations

9
Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications DOI Creative Commons
Xiaowen Xie, Weici Liu, Zhiyuan Yuan

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 8, 2025

Epigenomic modifications—such as DNA methylation, histone acetylation, and methylation—and their implications in tumorigenesis, progression, treatment have emerged a pivotal field cancer research. Tumors undergo metabolic reprogramming to sustain proliferation metastasis nutrient-deficient conditions, while suppressing anti-tumor immunity the tumor microenvironment (TME). Concurrently, immune cells within immunosuppressive TME adaptations, leading alterations function. The complicated interplay between metabolites epigenomic modulation has spotlighted significance of regulation immunometabolism. In this review, characteristics modification associated with tumors are systematically summarized alongside regulatory roles Classical emerging approaches delineated broaden boundaries research on crosstalk immunometabolism epigenomics. Furthermore, we discuss potential therapeutic strategies that target modulate modifications, highlighting burgeoning synergy therapies immunotherapy promising avenue for treatment.

Language: Английский

Citations

1
Tumor cell metabolic reprogramming and hypoxic immunosuppression: driving carcinogenesis to metastatic colonization DOI Creative Commons
Theodora Katopodi, Savvas Petanidis, Doxakis Anestakis

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 16, 2024

A significant factor in the antitumor immune response is increased metabolic reprogramming of immunological and malignant cells. Increasing data points to fact that cancer metabolism affects not just signaling, which essential for maintaining carcinogenesis survival, but also expression cells immune-related factors such as lactate, PGE2, arginine, IDO, regulate signaling mechanism. In reality, this energetic interaction between system tumor results competition ecosystem, limiting amount nutrients available causing microenvironmental acidosis, impairs ability operate. More intriguingly, different types use keep body self a state homeostasis. The process cell proliferation, differentiation, performance effector functions, crucial response, are currently being linked reprogramming. Here, we cover regulation by well potential strategies pathway targeting context anticancer immunotherapy. We discuss prospective immunotherapy-metabolic intervention combinations might be utilized maximize effectiveness current immunotherapy regimes.

Language: Английский

Citations

8
Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study DOI Creative Commons

Shuyi Ling,

Yuqing Dai,

Ruoxin Weng

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 12, 2024

Abstract Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships different types of disorders remain unclear in terms direction magnitude. We conducted a comprehensive investigation using two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish relationship genetically predicted risk various pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), cysts, abnormal uterine vaginal bleeding(AUB), endometriosis, leiomyoma uterus, infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting pregnancy, cervical cancer, uterine/endometrial cancer. analyzed substantial sample size, ranging from 111,831 210,870 individuals, employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, MR-PRESSO, estimate effects. Sensitivity analyses, Cochran's Q test, MR-Egger intercept leave-one-out funnel plots, were also ensure validity our results. Furthermore, factor analyses performed investigate potential mediators associated with these observed relationships. results demonstrated that genetic predisposition or dysthymia increased developing PCOS (OR = 1.43, 95% CI 1.28–1.59; P 6.66 × 10 –11 ), cysts 1.36, 1.20–1.55; 1.57 –6 AUB 1.41, 1.20–1.66; 3.01 –5 endometriosis 1.27–1.70; 2.21 –7 ) after Bonferroni correction, but no evidence for reverse causality. study did not find any supporting depression/dysthymia other In summary, provides specific findings emphasize importance management prevention treatment disorders, notably PCOS, AUB, endometriosis.

Language: Английский

Citations

7
Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts DOI Creative Commons
Tomas Koltai, Larry Fliegel

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 744 - 744

Published: June 6, 2024

Rarely has a chemical elicited as much controversy dichloroacetate (DCA). DCA was initially considered dangerous toxic industrial waste product, then potential treatment for lactic acidosis. However, the main controversies started in 2008 when found to have anti-cancer effects on experimental animals. These publications showed contradictory results vivo and vitro such that thorough consideration of this compound’s cancer is merited. Despite 50 years experimentation, DCA’s future therapeutics uncertain. Without adequate clinical trials health authorities’ approval, been introduced off-label treatments alternative medicine clinics Canada, Germany, other European countries. The lack well-planned its use by people without medical training discouraged scientific community. There are few studies DCA, many individual case reports. Case reports benefits against increasing recently. Furthermore, it shown synergizes with conventional repurposable drugs. Beyond classic target, pyruvate dehydrogenase kinase, new target molecules also recently discovered. findings renewed interest DCA. This paper explores whether existing evidence justifies further research role may play it.

Language: Английский

Citations

5
CD38 expression by neonatal human naïve CD4+T cells shapes their distinct metabolic state and high regulatory T cell potential DOI Open Access
Laura R. Dwyer,

Sean Clancy,

Victoire Gouirand

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Neonatal life is marked by rapid antigen exposure, necessitating establishment of peripheral immune tolerance via conversion naïve CD4 + T cells into regulatory (Tregs). Here, we demonstrate that increased Treg differentiation naive from human cord blood versus adult integrally linked to their unique metabolic profile and elevated expression the NADase, CD38. Early a preference for glycolysis, which directly facilitates generation. We reveal an age-dependent gradient in CD38 levels on show high contributes both glycolytic state potential neonatal cells, effects are mediated at least part NAD-dependent deacetylase SIRT1. Thus, early window humans critically enabled immunometabolic compartment.

Language: Английский

Citations

0
Metabolic reprogramming and immunological changes in the microenvironment of esophageal cancer: future directions and prospects DOI Creative Commons
Zhixun Guo, Jiali Ma, Jinqiu Zhang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 24, 2025

Background Esophageal cancer (EC) is the seventh-most prevalent worldwide and a significant contributor to cancer-related mortality. Metabolic reprogramming in tumors frequently coincides with aberrant immune function alterations, extensive research has demonstrated that perturbations energy metabolism within tumor microenvironment influence occurrence progression of esophageal cancer. Current treatment modalities for primarily include encompass chemotherapy limited array targeted therapies, which are hampered by toxicity drug resistance issues. Immunotherapy, particularly checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathway, exhibited promising results; however, substantial proportion patients remain unresponsive. The optimization these immunotherapies requires further investigation. Mounting evidence underscores importance modulating metabolic traits (TME) augment anti-tumor immunotherapy. Methods We selected relevant studies on cells based our searches MEDLINE PubMed, focusing screening experimental articles reviews related glucose metabolism, amino acid lipid as well their interactions cells, published last five years. analyzed discussed studies, while also expressing own insights opinions. Results A total 137 were included review: 21 focused cancer, 33 delved into immunology, 30 introduced responses, 17 relationship between both cells. Conclusion This article delves alterations TME EC, systematically synthesizes characteristics TME, dissects consolidates harnesses pertinent immunotherapy targets, goal enhancing thereby offering development novel therapeutic strategies.

Language: Английский

Citations

0