Macrophages in immunoregulation and therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 22, 2023

Abstract Macrophages exist in various tissues, several body cavities, and around mucosal surfaces are a vital part of the innate immune system for host defense against many pathogens cancers. possess binary M1/M2 macrophage polarization settings, which perform central role an array tasks via intrinsic signal cascades and, therefore, must be precisely regulated. Many crucial questions about signaling modulation yet to uncovered. In addition, clinical importance tumor-associated macrophages is becoming more widely recognized as significant progress has been made understanding their biology. Moreover, they integral tumor microenvironment, playing regulation wide variety processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis, immunosuppression, resistance chemotherapeutic checkpoint blockade immunotherapies. Herein, we discuss signaling, mechanical stresses modulation, metabolic pathways, mitochondrial transcriptional, epigenetic regulation. Furthermore, have broadly extended traps essential roles autophagy aging regulating functions. discussed recent advances macrophages-mediated autoimmune diseases tumorigenesis. Lastly, targeted therapy portray prospective targets therapeutic strategies health diseases.

Язык: Английский

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Metabolism, metabolites, and macrophages in cancer

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Июль 25, 2023

Abstract Tumour-associated macrophages (TAMs) are crucial components of the tumour microenvironment and play a significant role in development drug resistance by creating an immunosuppressive microenvironment. Macrophages essential both innate adaptive immune systems contribute to pathogen regulation organism homeostasis. Macrophage function polarization closely linked altered metabolism. Generally, M1 rely primarily on aerobic glycolysis, whereas M2 depend oxidative Metabolic studies have revealed that metabolic signature TAMs metabolites regulate TAMs. However, precise effects reprogramming tumours remain incompletely understood. In this review, we discuss impact pathways macrophage as well potential strategies for metabolism cancer treatment.

Язык: Английский

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Roles of the peroxisome proliferator-activated receptors (PPARs) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)

Pharmacological Research, Год журнала: 2023, Номер 192, С. 106786 - 106786

Опубликована: Май 3, 2023

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of phenotypes which start with simple steatosis and lipid accumulation in the hepatocytes - typical histological lesions characteristic. It may progress to non-alcoholic steatohepatitis (NASH) that is characterized by hepatic inflammation and/or fibrosis subsequent onset NAFLD-related cirrhosis hepatocellular carcinoma (HCC). Due central role metabolism, NAFLD regarded as result contribution metabolic abnormalities seen syndrome. Peroxisome proliferator-activated receptors (PPARs) has three subtypes, govern expression genes responsible for energy cellular development, inflammation, differentiation. The agonists PPARα, such fenofibrate clofibrate, have been used lipid-lowering drugs clinical practice. Thiazolidinediones (TZDs) ligands PPARγ, rosiglitazone pioglitazone, are also treatment type 2 diabetes (T2D) insulin resistance (IR). Increasing evidence suggests PPARβ/δ potential therapeutic effects improving sensitivity metabolism disorders. In addition, PPARs considered hypertension, atherosclerosis (AS) or diabetic nephropathy. Their crucial biological roles dictate significance PPARs-targeting medical research drug discovery. Here, it reviews activities, ligand selectivity functions family, discusses relationship between pathogenesis This will open new possibilities application medicine, provide idea related diseases.

Язык: Английский

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Cancer stem cells: advances in knowledge and implications for cancer therapy

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

Опубликована: Июль 5, 2024

Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.

Язык: Английский

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Metabolic dysfunction-associated fatty liver disease and implications for cardiovascular risk and disease prevention

Cardiovascular Diabetology, Год журнала: 2022, Номер 21(1)

Опубликована: Дек. 3, 2022

The newly proposed term "metabolic dysfunction-associated fatty liver disease" (MAFLD) is replacing the old "non-alcoholic (NAFLD) in many global regions, because it better reflects pathophysiology and cardiometabolic implications of this common disease. change terminology from NAFLD to MAFLD not simply a single-letter an acronym, since defined by set specific positive diagnostic criteria. In particular, definition specifically incorporates within classification recognized cardiovascular risk factors. Although convincing evidence supports significant association between both MAFLD, with increased CVD morbidity mortality, neither nor have received sufficient attention Cardiology community. fact, there paucity scientific guidelines focusing on burdensome disease professional societies. This Perspective article discusses rationale clinical relevance for Cardiologists definition.

Язык: Английский

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Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 152, С. 113208 - 113208

Опубликована: Май 31, 2022

This study aimed to reveal the classical signal pathways and important potential targets of traditional Chinese medicine (TCM) for treating Alzheimer's disease (AD), provide support further investigation on TCM its active ingredients.Literature survey was conducted using PubMed, Web Science, Google Scholar, CNKI, other databases, with "Alzheimer's disease," "traditional medicine," "medicinal herb," "Chinese "natural plant" as primary keywords.TCM could modulate related AD pathological progression, including NF-κB, Nrf2, JAK/STAT, ubiquitin-proteasome pathway, autophagy-lysosome pathway-related AMPK/mTOR, GSK-3/mTOR, PI3K/Akt/mTOR, well SIRT1 PPARα pathway. It regulate crosstalk between through a multitarget, thus maintaining chronic inflammatory interaction balance, inhibiting oxidative stress damage, regulating system function, modulating autophagy, eventually improving cognitive impairment in patients AD.TCM be multilevel, multitargeted, multifaceted prevent treat AD. In-depth research prevention treatment new ideas exploring pathogenesis developing anti-AD drugs.

Язык: Английский

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Bacteria‐Derived Outer‐Membrane Vesicles Hitchhike Neutrophils to Enhance Ischemic Stroke Therapy

Advanced Materials, Год журнала: 2023, Номер 35(38)

Опубликована: Июнь 26, 2023

Abstract The treatment of reperfusion injury after ischemic stroke remains unsatisfactory since the blood‐brain barrier (BBB) prevents most neuroprotective agents from entering brain. Here, a strategy is proposed based on bacteria‐derived outer‐membrane vesicle (OMV) hitchhiking neutrophils for enhanced brain delivery pioglitazone (PGZ) to treat stroke. By encapsulating PGZ into OMV, resulting OMV@PGZ nanoparticles inherit functions associated with bacterial outer membrane, making them ideal decoys neutrophil uptake. results show that simultaneously inhibits activation nucleotide oligomerization‐like receptor protein 3 (NLRP3) inflammasomes and ferroptosis reduces exert effect. Notably, transcription factors Pou2f1 Nrf1 oligodendrocytes are identified first time be involved in this process promoted neural repair by single‐nucleus RNA sequencing (snRNA‐seq).

Язык: Английский

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Ameliorating Mitochondrial Dysfunction of Neurons by Biomimetic Targeting Nanoparticles Mediated Mitochondrial Biogenesis to Boost the Therapy of Parkinson's Disease

Advanced Science, Год журнала: 2023, Номер 10(22)

Опубликована: Май 18, 2023

Abstract Mitochondrial dysfunction of neurons is the core pathogenesis incurable Parkinson's disease (PD). It crucial to ameliorate mitochondrial for boosting therapy PD. Herein, remarkable promotion biogenesis and improve treatment PD by using mitochondria‐targeted biomimetic nanoparticles, which are Cu 2‐ x Se‐based nanoparticles functionalized with curcumin wrapped DSPE‐PEG 2000 ‐TPP‐modified macrophage membrane (denoted as CSCCT NPs), reported. These can efficiently target mitochondria damaged in an inflammatory environment, mediate signaling pathway NAD + /SIRT1/PGC‐1 α /PPAR γ /NRF1/TFAM alleviate 1‐methyl‐4‐phenylpyridinium (MPP )‐induced neuronal toxicity. They reduce reactive oxygen species, restore potential (MMP), protect integrity respiratory chain, via promoting biogenesis, synergistically motor disorders anxiety behavior 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mice. This study demonstrates that targeting has a great mitochondria‐related diseases.

Язык: Английский

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A review of cardiovascular effects and underlying mechanisms of legacy and emerging per- and polyfluoroalkyl substances (PFAS)

Archives of Toxicology, Год журнала: 2023, Номер 97(5), С. 1195 - 1245

Опубликована: Март 22, 2023

Язык: Английский

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Treating NASH by targeting peroxisome proliferator-activated receptors

Journal of Hepatology, Год журнала: 2023, Номер 79(5), С. 1302 - 1316

Опубликована: Июль 17, 2023

Язык: Английский

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