Melatonin Engineering M2 Macrophage‐Derived Exosomes Mediate Endoplasmic Reticulum Stress and Immune Reprogramming for Periodontitis Therapy

Advanced Science, Год журнала: 2023, Номер 10(27)

Опубликована: Июль 14, 2023

Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play crucial role in inflammatory response. An appropriate timely transition from proinflammatory (M1) to anti-inflammatory (M2) indispensable for treating periodontitis. M2 macrophage-derived exosomes (M2-exos) can actively target sites modulate immune microenvironments, M2-exos effectively treat Excessive endoplasmic reticulum stress (ER stress) unfolded protein response (UPR) destructive pathological characteristics during periodontal bone loss. Although melatonin has antioxidant effects, studies focusing on ER modulation remain limited. This study fabricates engineered loading with (Mel@M2-exos) result, drive macrophage reprogramming M1 type, which resolves inflammation accelerated healing. Melatonin released Mel@M2-exos rescues osteogenic cementogenic differentiation capacity human ligament cells (hPDLCs) reducing excessive UPR. Injectable gelatin methacryloyl (GelMA) hydrogels sustained-release accelerate regeneration rats ligation-induced Taken together, engineering promising candidates tissue regeneration.

Язык: Английский

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Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets

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

Опубликована: Май 31, 2024

Abstract The immune response holds a pivotal role in cardiovascular disease development. As multifunctional cells of the innate system, macrophages play an essential initial inflammatory that occurs following injury, thereby inducing subsequent damage while also facilitating recovery. Meanwhile, diverse phenotypes and phenotypic alterations strongly associate with distinct types severity diseases, including coronary heart disease, valvular myocarditis, cardiomyopathy, failure, atherosclerosis aneurysm, which underscores importance investigating macrophage regulatory mechanisms within context specific diseases. Besides, recent strides single-cell sequencing technologies have revealed heterogeneity, cell–cell interactions, downstream therapeutic targets at higher resolution, brings new perspectives into macrophage-mediated potential Remarkably, myocardial fibrosis, prevalent characteristic most cardiac remains formidable clinical challenge, necessitating profound investigation impact on fibrosis In this review, we systematically summarize functional plasticity diseases unprecedented insights introduced by technologies, focus different causes characteristics especially relationship between inflammation (myocardial infarction, pressure overload, dilated diabetic cardiomyopathy aging) vascular injury (atherosclerosis aneurysm). Finally, highlight preclinical/clinical targeting strategies translational implications.

Язык: Английский

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M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2⁺ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair

Advanced Science, Год журнала: 2023, Номер 10(14)

Опубликована: Март 22, 2023

Abstract Tissue‐resident cardiac macrophage subsets mediate tissue inflammation and repair after acute myocardial infarction (AMI). CC chemokine receptor 2 (CCR2)‐expressing macrophages have phenotypical similarities to M1‐polarized macrophages, are pro‐inflammatory, recruit CCR2 + circulating monocytes infarcted myocardium. Small extracellular vesicles (sEV) from ̶ which phenotypically resemble M2‐polarized promote anti‐inflammatory activity repair. Here, the authors harvested M2 macrophage‐derived sEV (M2 EV ) bone‐marrow‐derived for intramyocardial injection recapitulation of sEV‐mediated in ischemic‐reperfusion (I/R) injured hearts. Rats pigs received sham surgery; I/R without treatment; or with autologous treatment. rescued function attenuated injury markers, infarct size, scar size. inhibited numbers, reduced monocyte‐derived recruitment sites, induced M1‐to‐M2 switching promoted neovascularization. Analysis microRNA content revealed abundant miR‐181b‐5p, regulated glucose uptake, glycolysis, mitigated mitochondrial reactive oxygen species generation. Functional blockade miR‐181b‐5p is detrimental beneficial actions resulted failure inhibit numbers Taken together, this investigation showed that function, improved repair, via miR‐181b‐5p‐dependent mechanisms, indicating an option cell‐free therapy AMI.

Язык: Английский

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Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Язык: Английский

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Myocardia‐Injected Synergistically Anti‐Apoptotic and Anti‐Inflammatory Poly(amino acid) Hydrogel Relieves Ischemia‐Reperfusion Injury

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Reperfusion therapy is the most effective treatment for acute myocardial infarction, but its efficacy frequently limited by ischemia‐reperfusion injury (IRI). While antioxidant and anti‐inflammatory therapies have shown significant potential in alleviating IRI, these strategies not yielded satisfactory clinical outcomes. For that, a thermo‐sensitive myocardial‐injectable poly(amino acid) hydrogel of methoxy poly(ethylene glycol) 45 ‐poly(L‐methionine 20 ‐ co ‐L‐alanine 10 ) (mPEG ‐P(Met ‐Ala ), PMA) loaded with FTY720 (PMA/FTY720) developed to address IRI through synergistic anti‐apoptotic effects. Upon injection into ischemic myocardium, PMA aqueous solution undergoes sol‐to‐gel phase transition gradually degrades response reactive oxygen species (ROS), releasing on demand. acts synergistically inhibit cardiomyocyte apoptosis modulate pro‐inflammatory M1 macrophage polarization toward M2 macrophages clearing ROS, thereby mitigating inflammatory promoting vascular regeneration. In rat model, PMA/FTY720 reduces apoptotic cell ratio 81.8%, increases density 34.0%, enhances left ventricular ejection fraction (LVEF) 12.8%. rabbit gel‐based sustained release enhanced LVEF an additional 7.2% compared individual treatment. summary, engineered effectively alleviates anti‐apoptosis anti‐inflammation actions, offering valuable treating IRI.

Язык: Английский

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Macrophage-driven cardiac inflammation and healing: insights from homeostasis and myocardial infarction

Cellular & Molecular Biology Letters, Год журнала: 2023, Номер 28(1)

Опубликована: Окт. 19, 2023

Abstract Early and prompt reperfusion therapy has markedly improved the survival rates among patients enduring myocardial infarction (MI). Nonetheless, resulting adverse remodeling subsequent onset of heart failure remain formidable clinical management challenges represent a primary cause disability in MI worldwide. Macrophages play crucial role immune system regulation wield profound influence over inflammatory repair process following MI, thereby dictating degree injury pathological remodeling. Despite numerous previous biological studies that established classical polarization model for macrophages, classifying them as either M1 pro-inflammatory or M2 pro-reparative this simplistic categorization falls short meeting precision medicine standards, hindering translational advancement research. Recently, advances single-cell sequencing technology have facilitated more exploration macrophage heterogeneity plasticity, opening avenues development targeted interventions to address macrophage-related factors aftermath MI. In review, we provide summary origins, tissue distribution, classification, surface markers. Furthermore, delve into multifaceted roles macrophages maintaining cardiac homeostasis regulating inflammation during post-MI period.

Язык: Английский

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A paintable and adhesive hydrogel cardiac patch with sustained release of ANGPTL4 for infarcted heart repair

Bioactive Materials, Год журнала: 2023, Номер 31, С. 395 - 407

Опубликована: Авг. 29, 2023

The infarcted heart undergoes irreversible pathological remodeling after reperfusion involving left ventricle dilation and excessive inflammatory reactions in the heart, frequently leading to fatal functional damage. Extensive attempts have been made attenuate hearts using cardiac patches anti-inflammatory drug delivery. In this study, we developed a paintable adhesive hydrogel patch dextran-aldehyde (dex-ald) gelatin, incorporating protein, ANGPTL4, into for sustained release directly alleviate inflammation. We optimized material composition, including polymer concentration molecular weight, achieve paintable, 10% gelatin 5% dex-ald, which displayed in-situ gel formation within 135 s, tissue-like modulus (40.5 kPa), suitable tissue adhesiveness (4.3 excellent mechanical stability. ANGPTL4 was continuously released from gelatin/dex-ald without substantial burst release. could be conveniently painted onto beating degraded vivo. Moreover, vivo studies animal models of acute myocardial infarction revealed that our containing significantly improved repair, evaluated by echocardiography histological evaluation. tissues treated with ANGPTL4-loaded exhibited increased vascularization, reduced macrophages, structural maturation cells. Our novel system, allows facile paintability, appropriate adhesiveness, drugs, will serve as an effective platform repair various tissues, muscle, cartilage.

Язык: Английский

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Engineered M2 macrophage-derived extracellular vesicles with platelet membrane fusion for targeted therapy of atherosclerosis

Bioactive Materials, Год журнала: 2024, Номер 35, С. 447 - 460

Опубликована: Фев. 17, 2024

Atherosclerosis is featured as chronic low-grade inflammation in the arteries, which leads to formation of plaques rich lipids. M2 macrophage-derived extracellular vesicles (M

Язык: Английский

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Self-Adapting Biomass Hydrogel Embodied with miRNA Immunoregulation and Long-Term Bacterial Eradiation for Synergistic Chronic Wound Therapy

ACS Nano, Год журнала: 2024, Номер 18(28), С. 18379 - 18392

Опубликована: Июль 2, 2024

Chronic wound rescue is critical for diabetic patients but challenging to achieve with a specific and long-term strategy. The prolonged bacterial inflammation particularly prevalent in hyperglycemia-induced wounds, usually leading severe tissue damage. Such trend could further suffer from an environmental suitability provided by macrophages persisting Staphylococcus aureus (S. aureus) even deteriorate their mutual reinforcement. However, the strategy of both suppressing bacteria growth immunoreprogramming inflammatory type break vicious harm healing still lacking. Here, self-adapting biomass carboxymethyl chitosan (CMC) hydrogel comprising immunomodulatory nanoparticles reported Gram-negative/Gram-positive elimination anti-inflammatory cytokines induction ameliorate cutaneous microenvironment. Mechanistically, antibacterial peptides CMCs synergistically result inhibition against methicillin-resistant S. (MRSA) over period 7 days, miR-301a reprograms M2 macrophage via PTEN/PI3Kγ/mTOR signaling pathway, consequently mitigating promoting angiogenesis rats. In this vein, immunoregulatory promising all-biomass dressing ensuring biocompatibility, providing perspective regenerate damaged tissue, repairing chronic wounds on skin.

Язык: Английский

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Cardiac resident macrophages in cardiovascular disease: from physiology to pathology

Heart, Год журнала: 2025, Номер unknown, С. heartjnl - 324333

Опубликована: Март 4, 2025

Cardiovascular disease (CVD) is the leading cause of death and burden worldwide. Macrophages are important components internal immune cells, which profoundly affects environmental homeostasis repair after injury. Cardiac resident macrophages have been shown to regulate a variety myocardial physiology pathological activities. Homeostatic in heart promote angiogenesis, remove ageing dying cells participate cardiac electrical conduction. However, role still not fully understood despite growing attention they received. This review provides an overview macrophage biology highlights prominent emerging interrelationships functions between CVD, aiming prove description functional diversity different CVD explore potential options them. may provide opportunities for successful therapeutic interventions improve prognosis patients with CVD.

Язык: Английский

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