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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The immunology of multiple sclerosis

Nature reviews. Immunology, Год журнала: 2022, Номер 22(12), С. 734 - 750

Опубликована: Май 4, 2022

Язык: Английский

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Exploring treatment options in cancer: Tumor treatment strategies

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

Опубликована: Июль 17, 2024

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive remarkable transformation. Emerging fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, gene therapy. These cutting-edge not only afford personalized precise targeting, but also provide enhanced comfort potential to impede disease progression. Nonetheless, it is acknowledged that these strategies still harbour untapped for further advancement. Gaining understanding merits limitations holds promise offering novel perspectives clinical practice foundational research endeavours. In this review, we discussed different modalities, including drugs, peptide antibody cell therapy, It will detailed explanation each method, addressing their status development, challenges, solutions. The aim assist clinicians researchers in gaining deeper diverse options, enabling them carry out effective advance more efficiently.

Язык: Английский

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Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Ноя. 25, 2021

Rheumatoid arthritis is an autoimmune disease that exhibits significant clinical heterogeneity. There are various treatments for rheumatoid arthritis, including disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids, non-steroidal anti-inflammatory (NSAIDs), and inflammatory cytokine inhibitors (ICI), typically associated with differentiated effects characteristics. Personalized responsiveness observed to the standard treatment due pathophysiological heterogeneity in resulting overall poor prognosis. Understanding role of individual variation cellular molecular mechanisms related will considerably improve care patient outcomes. In this review, we discuss source derived from genetic, molecular, their possible impact on precision medicine personalized arthritis. We provide emphasized description mast cells, monocyte cell, macrophage fibroblast-like synoviocytes and, interactions within immune cells cytokines, as well potential a new therapeutic target develop novel approach. Finally, summarize latest trials options suggestive framework implementing preclinical experimental results into practice.

Язык: Английский

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Dynamic lipidome alterations associated with human health, disease and ageing

Nature Metabolism, Год журнала: 2023, Номер 5(9), С. 1578 - 1594

Опубликована: Сен. 11, 2023

Abstract Lipids can be of endogenous or exogenous origin and affect diverse biological functions, including cell membrane maintenance, energy management cellular signalling. Here, we report >800 lipid species, many which are associated with health-to-disease transitions in diabetes, ageing inflammation, as well cytokine–lipidome networks. We performed comprehensive longitudinal lipidomic profiling analysed >1,500 plasma samples from 112 participants followed for up to 9 years (average 3.2 years) define the distinct physiological roles complex subclasses, large small triacylglycerols, ester- ether-linked phosphatidylethanolamines, lysophosphatidylcholines, lysophosphatidylethanolamines, cholesterol esters ceramides. Our findings reveal dynamic changes lipidome during respiratory viral infection, insulin resistance ageing, suggesting that lipids may have immune homoeostasis inflammation regulation. Individuals exhibit disturbed homoeostasis, altered associations between clinical markers, accelerated specific subclasses ageing. dataset based on deep offers insights into personalized metabolic health potentially guiding future monitoring intervention strategies.

Язык: Английский

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High-throughput prediction of protein conformational distributions with subsampled AlphaFold2

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 27, 2024

Abstract This paper presents an innovative approach for predicting the relative populations of protein conformations using AlphaFold 2, AI-powered method that has revolutionized biology by enabling accurate prediction structures. While 2 shown exceptional accuracy and speed, it is designed to predict proteins’ ground state limited in its ability conformational landscapes. Here, we demonstrate how can directly different subsampling multiple sequence alignments. We tested our against nuclear magnetic resonance experiments on two proteins with drastically amounts available data, Abl1 kinase granulocyte-macrophage colony-stimulating factor, predicted changes their more than 80% accuracy. Our worked best when used qualitatively effects mutations or evolution landscape well-populated states proteins. It thus offers a fast cost-effective way at even single-point mutation resolution, making useful tool pharmacology, analysis experimental results, evolution.

Язык: Английский

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Acellular cardiac scaffolds enriched with MSC-derived extracellular vesicles limit ventricular remodelling and exert local and systemic immunomodulation in a myocardial infarction porcine model

Theranostics, Год журнала: 2022, Номер 12(10), С. 4656 - 4670

Опубликована: Янв. 1, 2022

Rationale: Extracellular vesicles (EVs) from mesenchymal stromal cell (MSC) are a potential therapy for cardiac healing after myocardial infarction (MI). Nevertheless, neither their efficient administration nor therapeutic mechanisms fully elucidated. Here, we evaluate the preclinical efficacy of tissue engineering approach to locally deliver porcine adipose MSC-EV (cATMSC-EV) in an acute MI pig model. Methods: After by permanent ligation coronary artery, pigs (n = 24) were randomized Untreated or treated groups with decellularised pericardial scaffold filled peptide hydrogel and cATMSC-EV purified size exclusion chromatography (EV-Treated group) buffer (Control group), placed over post-infarcted myocardium. Results: 30 days, MRI showed improved function EV-Treated animals, significantly higher right ventricle ejection fraction (+20.8% EV-Treated; p 0.026), less dilatation, indicating remodelling. Scar was reduced, fibrosis distal myocardium (-42.6% Col I vs Untreated; 0.03), 2-fold increase vascular density (EV-Treated; 0.019) CCL2 transcription infarct core. EV-treated animals had macrophage infiltration core (-31.7% CD163+ cells/field but 5.8 times more expressing anti-inflammatory CD73 (p 0.015). Systemically, delivered also triggered systemic effect, doubling circulating IL-1ra 0.01), reducing PBMC rush 2d post-MI, TNFα GM-CSF levels at 30d modulating CD73+ CCR2+ monocyte populations, related immunomodulation modulation. Conclusions: These results highlight hallmarks ischemic injury repair MI.

Язык: Английский

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The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Май 31, 2022

Chronic spontaneous urticaria (CSU) is defined as recurrent episodes of wheal development and/or angioedema for more than six weeks and at least twice a week. The core link in the pathogenesis CSU activation mast cells, T eosinophils, other immune cells infiltrating around small venules lesion. Increased vascular permeability, vasodilatation, recruitment inflammatory directly depend on cell mediators’ release. Complex regulatory systems tightly influence critical roles local microenvironment. bias toward Th2 inflammation autoantibodies derived from B histamine expressed by basophils, initiation extrinsic coagulation pathway eosinophils or monocytes exerts powerful modulatory influences cells. Cell-to-cell interactions between eosinophils/T also are regulators their function may involve CSU’s pathomechanism. This review summarizes up-to-date knowledge regarding crosstalk providing impetus to develop new research concepts treatment strategies CSU.

Язык: Английский

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Neutrophils in Inflammatory Diseases: Unraveling the Impact of Their Derived Molecules and Heterogeneity

Cells, Год журнала: 2023, Номер 12(22), С. 2621 - 2621

Опубликована: Ноя. 13, 2023

Inflammatory diseases involve numerous disorders and medical conditions defined by an insufficient level of self-tolerance. These evolve over the course a multi-step process through which environmental variables play crucial role in emergence aberrant innate adaptive immunological responses. According to experimental data accumulated past decade, neutrophils significant as effector cells immunity. However, are also involved progression participation onset maintenance immune-mediated dysregulation releasing neutrophil-derived molecules forming neutrophil extracellular traps, ultimately causing destruction tissues. Additionally, have wide variety functional heterogeneity with adverse effects on inflammatory diseases. complicated biology its remains unclear. Moreover, considered intriguing target interventional therapies due their multifaceted number Several approaches been developed therapeutically neutrophils, involving strategies improve function, various compounds inhibitors currently undergoing clinical trials, although challenges contradictions field persist. This review outlines current literature roles molecules, pathogenesis autoimmune potential future therapeutic strategies.

Язык: Английский

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Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

Brain Sciences, Год журнала: 2023, Номер 13(4), С. 632 - 632

Опубликована: Апрель 7, 2023

Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer's. Microglia are the brain's primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds anti-inflammatory antioxidant properties, epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related diseases involving activated microglia cells. The objective of current study was to examine molecular targets underlying effects EGCG in BV-2 cells were grown, stimulated, treated EGCG. Cytotoxicity nitric oxide (NO) production evaluated. Immunoassay, PCR array, WES™ Technology utilized evaluate inflammatory, neuroprotective modulators well signaling pathways involved mechanistic action neuroinflammation. Our findings showed that significantly inhibited mediator NO LPS-stimulated In addition, ELISA analysis revealed decreases cytokine IL-6 while it increases TNF-α. array downregulated MIF, CCL-2, CSF2. It also upregulated IL-3, IL-11, TNFS10. Furthermore, inflammatory mRNA expression mTOR, NF-κB2, STAT1, Akt3, CCL5, SMAD3 upregulating Ins2, Pld2, A20/TNFAIP3, GAB1. Additionally, reduced relative protein Akt3. These suggest be used its prevent diseases.

Язык: Английский

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