Inhibition of Mitochondrial Succinate Dehydrogenase with Dimethyl Malonate Promotes M2 Macrophage Polarization by Enhancing STAT6 Activation

Inflammation, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Язык: Английский

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Cranial bone maneuver ameliorates Alzheimer's disease pathology via enhancing meningeal lymphatic drainage function

Alzheimer s & Dementia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Abstract INTRODUCTION Alzheimer's disease (AD) is a progressive neurodegenerative and the leading cause of dementia. Recent research highlights meningeal lymphatics as key regulators in neurological diseases, suggesting that enhancing their drainage function could be potential therapeutic strategy for AD. Our proof‐of‐concept study demonstrated cranial bone transport can improve lymphatic promote ischemic stroke recovery. METHODS This defined maneuver (CBM) technique. After osteotomy, small circular flap was made attached to an external fixator subsequent controlled fashion period using 5xFAD mice. RESULTS CBM treatment improved memory functions, reduced amyloid deposits, promoted function. induced cascades inflammatory lymphangiogenic processes skull meninges. Meningeal are indispensable elements effects CBM. DISCUSSION might promising innovative therapy AD management, warranting further clinical investigation. Highlights Cranial alleviated deficits depositions. lymphangiogenesis The beneficial lasted long time following procedures. vessels effects.

Язык: Английский

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Acute contact with profibrotic macrophages mechanically activates fibroblasts via αvβ3 integrin–mediated engagement of Piezo1

Science Advances, Год журнала: 2024, Номер 10(43)

Опубликована: Окт. 23, 2024

Fibrosis—excessive scarring after injury—causes >40% of disease-related deaths worldwide. In this misguided repair process, activated fibroblasts drive the destruction organ architecture by accumulating and contracting extracellular matrix. The resulting stiff scar tissue, in turn, enhances fibroblast contraction—bearing question how positive feedback loop begins. We show that direct contact with profibrotic but not proinflammatory macrophages triggers acute contractions. contractile response depends on αvβ3 integrin expression Piezo1 fibroblasts. touch elevates cytosolic calcium within seconds, followed translocation transcription cofactors nuclear factor T cells 1 Yes-associated protein, which activation hours. Intriguingly, induce mechanical stress soft matrix alone suppresses their spontaneous activation. propose suitable mechanically kick-starts an otherwise nonpermissive environment. molecular components mediating macrophage-fibroblast mechanotransduction are potential targets for antifibrosis strategies.

Язык: Английский

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Eu-Doped TiO₂ Coatings via One-Step In Situ Preparation Enhance Macrophage Polarization and Osseointegration of Implants

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер 17(6), С. 8886 - 8900

Опубликована: Янв. 31, 2025

The controllable regulation of immune and osteogenic processes plays a critical role in the modification biocompatible materials for tissue regeneration. In this study, titanium dioxide-europium coatings (MAO/Eu) were prepared on surface alloy (Ti-6Al-4V) via one-step process combining microarc oxidation (MAO) situ doping. incorporation Eu significantly improved hydrophilic mechanical properties TiO2 without altering their morphology. presence effectively stimulated calcium influx macrophages activated β-catenin through wnt/β-catenin signaling pathway. Consequently, macrophage M2 polarization was accelerated overexpression prostaglandin E2 (PGE2). Additionally, Ca2+ promoted differentiation MC3T3-E1 cells synergistic upregulation transcription factors (e.g., AP-1, BMP-2). vivo studies demonstrated that MAO/Eu enhanced osseointegration compared with group. Therefore, shows promising potential as an ideal coating implants offers effective immunomodulatory strategies improves bone integration.

Язык: Английский

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Advanced Microarrays as Heterogeneous Force‐Remodeling Coordinator to Orchestrate Nuclear Configuration and Force‐Sensing Mechanotransduction in Stem Cells

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Integrin and focal adhesion can regulate cytoskeleton distribution to govern actin-related force remodeling play an important role in nuclear configuration force-sensing mechanotransduction of stem cells. However, further exploration the interaction between actinin complex myosin, kinetics, molecular mechanism structures nucleate within engineered cells is vague. An extensive comprehension cell morphogenesis, remodeling, essential reveal basic physical principles polymerization force-related signaling delivery. Advanced microarrays are designed determine heterogeneous morphology behaviors The heterogeneity from transferred into nuclei by evaluation Lamins, YAP, BrdU expression. Tuning activation proteins nucleators adjust mechanics may be underlying change response its physiological microarrayed

Язык: Английский

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Macrophage variants in laboratory research: most are well done, but some are RAW

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Окт. 9, 2024

Macrophages play a pivotal role in the innate immune response. While their most characteristic function is phagocytosis, it important not to solely characterize macrophages by this activity. Their crucial roles body development, homeostasis, repair, and responses against pathogens necessitate broader understanding. exhibit remarkable plasticity, allowing them modify functional characteristics response tissue microenvironment (tissue type, presence of or inflammation, specific signals from neighboring cells) swiftly. there no single defined "macrophage" entity, diverse array macrophage types because ontogeny involves differentiation progenitor cells into tissue-resident macrophages, as well recruitment circulating monocytes tissue-specific cues. In addition, continuously sense respond environmental cues conditions, adjusting metabolic states accordingly. Consequently, paramount importance comprehend heterogeneous origins functions employed

Язык: Английский

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Mild Hyperthermia Accelerates Bone Repair by Dynamically Regulating iNOS/Arg1 Balance in the Early Stage

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 31, 2024

Mild hyperthermia therapy has garnered interest as an adjunctive treatment for bone repair. However, its optimal timing, duration, and underlying mechanisms remain unclear. In this study, how mild supports repair during the early stages is assesed. These findings reveal that accelerates regeneration by dynamically regulating inducible nitric oxide synthase/arginase 1 (iNOS/Arg1) balance. This process involves macrophage polarization to M1 phenotype through iNOS activation, followed a rapid transition M2 Arg1 activation after 3 days of sustained hyperthermia. RNA-Seq reveals single day induced immune alterations aligned with inflammatory phase repair, characterized osteoclast cell recruitment, neovascularization, thereby preparing phase. Experiments involving subcutaneous abscesses, embedding, critical cranial defects further confirm regulates phenotypes. regulation enhances antibacterial activity, promotes angiogenesis, facilitates from inflammation ultimately accelerating bone-defect study first elucidate dual temporal effects on regulation, offering insights into timing duration photothermal following surgery.

Язык: Английский

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The Intersection between Immune System and Idiopathic Pulmonary Fibrosis—A Concise Review

Deleted Journal, Год журнала: 2025, Номер 3(1), С. 10004 - 10004

Опубликована: Янв. 1, 2025

Idiopathic pulmonary fibrosis (IPF) is marked by progressive alveolar destruction, impaired tissue regeneration, and relentless fibrogenesis, culminating in respiratory failure death. A diverse array of resident non-resident cells within the lung contribute to disease pathogenesis. Notably, immune cells, both recruited, respond cues from sites injury undergoing phenotypic transitions producing a wide range mediators that influence, initiate, or dictate function, dysfunction, key effector IPF pathology, such as epithelial fibroblasts, capillary endothelial cells. The role system has undergone an interesting evolution, oscillating initial enthusiasm skepticism, now renewed focus. This shift reflects past failures immune-targeting therapies for unprecedented insights into cell heterogeneity provided emerging technologies. In this article, we review historical evolution perspectives on system's pathogenesis examine lessons learned previous therapeutic targeting responses. We discuss major types implicated progression, highlighting their mechanisms action. Finally, identify knowledge gaps propose future directions research IPF.

Язык: Английский

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Tropomodulin1 Regulates the Biomechanical Changes in Macrophages Induced by Matrix Stiffness

Mechanobiology in Medicine, Год журнала: 2025, Номер 3(2), С. 100117 - 100117

Опубликована: Фев. 20, 2025

The monocyte/macrophage infiltration plays critical roles in the development of atherosclerosis. Arterial stiffness is a cholesterol-independent risk factor for cardiovascular events. regulation arterial on biomechanics macrophages and its underlying mechanism remains unclear. We prepared polyacrylamide gels with low high that corresponded to healthy diseased blood vessels, respectively. found cultured stiff matrix had increased rigidity migration ability compared those soft matrix. An actin capping protein, tropomodulin1 (Tmod1) was upregulated by arteries stiffness. Further analyses showed deficiency Tmod1 completely or partially prevented changes polymerization, cell adhesion spreading induced Overexpression enhanced involved vinculin expression formation focal Finally, retarded atherosclerotic plaques vessels results suggest key regulator macrophage substrate. present work will help us understand biomechanical mechanisms

Язык: Английский

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Molecular mechanism on autophagy associated cardiovascular dysfunction in Drosophila melanogaster

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 3, 2025

As a highly conserved cellular process, autophagy has been the focus of extensive research due to its critical role in maintaining homeostasis and implications cardiovascular pathogenesis. The decline muscular function, along with neuronal system, increased sensitivity stress have recognized multiple animal models. Autophagic defects architecture dysfunction linked both physiological pathological conditions heart mammals Drosophila . In this review, we systematically analyze autophagy-associated pathways hearts fruit flies aim provide comprehensive understanding for developing potential treatments patients effective strategies agricultural applications. This analysis elucidates molecular mechanisms function under , offering significant insights into development diseases. loss key proteins, including transmembrane protein Atg9 partners Atg2 or Atg18, DmSestrin, leads cardiac hypertrophy structural abnormalities resembling age-dependent deterioration function. Members autophagy-related (Atg) gene family, nuclear skeletal lamins, mechanistic mammalian target rapamycin (mTOR) signaling are critically influential activation shown suppress laminopathy. mTORC1/C2 complexes, axis Atg2-AMPK/Sirt1/PGC-1α pathway, essential flies, governing development, growth, maturation, maintenance homeostasis. beneficial effects several interventions that enhance exercise cold stress, can influence autophagy-dependent TOR activity serine/threonine kinase Exercise increase when it is deficient inhibit excessive, highlighting dual health. review evaluates functional significance heart, particularly context relation mTORC-associated pathways. It contrasts underlying mammals. evolutionary conservation underscores value as model broader across species. study not only deepens our autophagy’s but also provides theoretical foundation application pest control.

Язык: Английский

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