Metabolic regulation of the immune system in health and diseases: mechanisms and interventions

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 9, 2024

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes functions of immune cells. The regulation system is important in pathogenesis progression numerous diseases, such as cancers, autoimmune diseases diseases. concept immunometabolism was introduced over a decade ago to elucidate intricate interplay between metabolism immunity. definition has expanded from chronic low-grade inflammation reprogramming cells various With being proposed developed, can be gradually summarized becomes more clearer. In context many cancer, disease, occurs inducing proinflammatory or anti-inflammatory effects. phenotypic functional changes caused by further affect development Based on experimental results, targeting cellular promising therapy. this review, we focus introduce their pathways reprogramming, summarize how these effects We thoroughly explore targets treatments based existing studies. challenges translating results into clinical applications field are also summarized. believe that better understanding health will improve management most

Язык: Английский

---

Innate immunity of vascular smooth muscle cells contributes to two-wave inflammation in atherosclerosis, twin-peak inflammation in aortic aneurysms and trans-differentiation potential into 25 cell types

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 24, 2024

Introduction Vascular smooth muscle cells (VSMCs) are the predominant cell type in medial layer of aorta, which plays a critical role aortic diseases. Innate immunity is main driving force for cardiovascular Methods To determine roles innate VSMC and pathologies, we performed transcriptome analyses on aortas from ApoE –/– angiotensin II (Ang II)-induced aneurysm (AAA) time course, atherosclerosis as well VSMCs stimulated with danger-associated molecular patterns (DAMPs). Results We made significant findings: 1) 95% 45% upregulated immune pathways (UIIPs, based data 1226 genes) Ang II-induced AAA at 7 days were different that 14 28 days, respectively; showed twin peaks UIIPs major peak minor days; 2) all 6 weeks 32 78 (two waves); 3) additional 12 lists immune-related genes 1325 cytokine chemokine genes, 2022 plasma membrane protein 373 clusters differentiation (CD) marker 280 nuclear 1425 nucleoli 6750 nucleoplasm 1496 transcription factors (TFs) including 15 pioneer TFs, 164 histone modification enzymes, 102 oxidative death 68 necrotic 47 efferocytosis confirmed two-wave inflammation twin-peak AAA; 4) DAMPs-stimulated judged by upregulation lists; 5) increased trans-differentiation potential upregulating not only some 82 markers VSMC-plastic types, fibroblast, osteogenic, myofibroblast, macrophage, adipocyte, foam cell, mesenchymal but also 18 new types (out 79 human 8065 markers); 6) analysis gene deficient transcriptomes indicated antioxidant factor NRF2 suppresses, however, other five inflammatory master regulators, AHR, NF-KB, NOX (ROS enzyme), PERK, SET7 promote twelve atherosclerosis, AAA, DAMP-stimulated VSMCs; 7) both trained tolerance-promoting metabolite itaconate contributed to cytokines AAA. Discussion Our findings have provided novel insights responses stresses development immunology therapeutic targets treating those cerebrovascular

Язык: Английский

---

Hexokinase 2-mediated metabolic stress and inflammation burden of liver macrophages via histone lactylation in MASLD

Cell Reports, Год журнала: 2025, Номер 44(3), С. 115350 - 115350

Опубликована: Фев. 25, 2025

Язык: Английский

---

Treatment of liver fibrosis: Past, current, and future

World Journal of Hepatology, Год журнала: 2023, Номер 15(6), С. 755 - 774

Опубликована: Июнь 25, 2023

Liver fibrosis accompanies the progression of chronic liver diseases independent etiologies, such as hepatitis viral infection, alcohol consumption, and metabolic-associated fatty disease. It is commonly associated with injury, inflammation, cell death. characterized by abnormal accumulation extracellular matrix components that are expressed myofibroblasts collagens alpha-smooth actin proteins. Activated hepatic stellate cells contribute to major population myofibroblasts. Many treatments for have been investigated in clinical trials, including dietary supplementation (e.g., vitamin C), biological treatment simtuzumab), drug pegbelfermin natural herbs), genetic regulation non-coding RNAs), transplantation stem hematopoietic cells). However, none these has approved Food Drug Administration. The efficacy can be evaluated histological staining methods, imaging serum biomarkers, well scoring systems, fibrosis-4 index, aspartate aminotransferase platelet ratio, non-alcoholic disease score. Furthermore, reverse slowly frequently impossible advanced or cirrhosis. To avoid life-threatening stage fibrosis, anti-fibrotic treatments, especially combined behavior prevention, treatment, drugs herb medicines, needed. This review summarizes past studies current future fibrosis.

Язык: Английский

---

Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 30, 2024

In the realm of cancer research, tumor microenvironment (TME) plays a crucial role in initiation and progression, shaped by complex interactions between cells surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted various cellular constituents within TME, including immune cells, cancer-associated fibroblasts, themselves. These cytokines facilitate intricate communication networks that significantly influence initiation, metastasis, suppression. Pyroptosis contributes to TME remodeling promoting release pro-inflammatory sustaining chronic inflammation, impacting processes such escape angiogenesis. However, challenges remain due interplay among cytokines, pyroptosis, along with dual effects pyroptosis on progression therapy-related complications like cytokine syndrome. Unraveling these complexities could strategies balance inflammatory responses while minimizing tissue damage during therapy. This review delves into crosstalk elucidating their contribution metastasis. By synthesizing emerging therapeutic targets innovative technologies concerning this aims provide novel insights enhance treatment outcomes for patients.

Язык: Английский

---

Protein-rich foods, sea foods, and gut microbiota amplify immune responses in chronic diseases and cancers – Targeting PERK as a novel therapeutic strategy for chronic inflammatory diseases, neurodegenerative disorders, and cancer

Pharmacology & Therapeutics, Год журнала: 2024, Номер 255, С. 108604 - 108604

Опубликована: Фев. 13, 2024

Язык: Английский

---

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

Metabolites, Год журнала: 2024, Номер 14(4), С. 218 - 218

Опубликована: Апрель 12, 2024

Metabolic-associated fatty liver disease (MAFLD), characterized primarily by hepatic steatosis, has become the most prevalent worldwide, affecting approximately two-fifths of global population. The pathogenesis MAFLD is extremely complex, and to date, there are no approved therapeutic drugs for clinical use. Considerable evidence indicates that various metabolic disorders play a pivotal role in progression MAFLD, including lipids, carbohydrates, amino acids, micronutrients. In recent years, medicinal properties natural products have attracted widespread attention, numerous studies reported their efficacy ameliorating subsequently alleviating MAFLD. This review aims summarize metabolic-associated pathological mechanisms as well regulate pathways alleviate

Язык: Английский

---

Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(24), С. 17514 - 17514

Опубликована: Дек. 15, 2023

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common in Western countries and the major cause of cirrhosis or hepatocellular carcinoma (HCC) addition to viral hepatitis recent decades. Furthermore, studies have shown that NAFLD is inextricably linked development extrahepatic diseases. However, there currently no effective treatment cure NAFLD. In addition, 2020, was renamed metabolic dysfunction (MAFLD) show its pathogenesis closely related disorders. Recent reported MAFLD associated with mitochondrial hepatocytes hepatic stellate cells (HSCs). Simultaneously, stress caused by structural functional disorders stimulates occurrence accumulation fat lipo-toxicity HSCs. interaction between liver-gut axis also a new point during MAFLD. this review, we summarize effects several potential strategies for MAFLD, including antioxidants, reagents, intestinal microorganisms metabolites.

Язык: Английский

---

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 6, 2024

Macrophages play a critical role in innate immunity, with approximately 90% of the total macrophage population human body residing liver. This encompasses both resident and infiltrating macrophages. Recent studies highlight pivotal liver macrophages various aspects such as inflammation, regeneration, immune regulation. A novel pro-inflammatory programmed cell death, pyroptosis, initially identified macrophages, has garnered substantial attention since its discovery. Studies investigating pyroptosis inflammation progression have particularly centered around In diseases, plays an important driving inflammatory response, facilitating fibrotic process, promoting tumor progression. Notably, cannot be understated. review primarily focuses on diseases. Additionally, it underscores therapeutic potential inherent targeting pyroptosis.

Язык: Английский

---

Targeting cell death in NAFLD: mechanisms and targeted therapies

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Сен. 7, 2024

Язык: Английский

---