Transcriptomic and Multi-scale Network Analyses Reveal Key Drivers of Cardiovascular Disease DOI Creative Commons
Bat‐Ider Tumenbayar, Khanh Pham, John C. Biber

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

ABSTRACT Cardiovascular diseases (CVDs) and pathologies are often driven by changes in molecular signaling communication, as well cellular tissue components, particularly those involving the extracellular matrix (ECM), cytoskeleton, immune response. The fine-wire vascular injury model is commonly used to study neointimal hyperplasia vessel stiffening, but it not typically considered a for CVDs. In this paper, we hypothesize that induces gene expression, biological processes similar observed CVDs at both transcriptome protein levels. To investigate this, analyzed expression microarray datasets from injured uninjured femoral arteries mice two weeks post-injury, identifying 1,467 significantly differentially expressed genes involved several such including vaso-occlusion, arrhythmia, atherosclerosis. We further constructed protein-protein interaction network with seven functionally distinct clusters, notable enrichment ECM, metabolic processes, actin-based process, Significant communications were between most prominently among ECM cytoskeleton organizations, inflammation, cell cycle. Machine Learning Disease pathway analysis revealed injury-induced crosstalk remodeling response clusters contributed aortic aneurysm, neovascularization of choroid, kidney failure. Additionally, found interactions actin cytoskeletal reorganization linked cardiac damage, carotid artery occlusion, lesions. Overall, through multi-scale bioinformatic analyses, demonstrated robustness eliciting transcriptomic associated CVDs, highlighting its potential use cardiovascular research.

Language: Английский

Inhibition of Mitochondrial Succinate Dehydrogenase with Dimethyl Malonate Promotes M2 Macrophage Polarization by Enhancing STAT6 Activation DOI
Chaowen He, Pengfei Chen, Ning Li

et al.

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Language: Английский

Citations

4
Cranial bone maneuver ameliorates Alzheimer's disease pathology via enhancing meningeal lymphatic drainage function DOI Creative Commons
Xuan Lu, Shanshan Bai, Feng Lu

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

2
Eu-Doped TiO2 Coatings via One-Step In Situ Preparation Enhance Macrophage Polarization and Osseointegration of Implants DOI
Baoping Zhang,

H. Qu,

Zhidong Zhang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: 17(6), P. 8886 - 8900

Published: Jan. 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.

Language: Английский

Citations

1
Advanced Microarrays as Heterogeneous Force‐Remodeling Coordinator to Orchestrate Nuclear Configuration and Force‐Sensing Mechanotransduction in Stem Cells DOI Creative Commons
Nana Wang,

Yan Hou,

Xin Lin

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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

Language: Английский

Citations

1
Acute contact with profibrotic macrophages mechanically activates fibroblasts via αvβ3 integrin–mediated engagement of Piezo1 DOI Creative Commons
Maya Ezzo,

Klaus‐Dieter Spindler,

J. Wang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(43)

Published: Oct. 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.

Language: Английский

Citations

7
Macrophage variants in laboratory research: most are well done, but some are RAW DOI Creative Commons
Marc Herb, Valentin Schatz, Karina Hadrian

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Oct. 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

Language: Английский

Citations

5
Pro-Inflammatory Response to Macrotextured Silicone Implant Wear Debris DOI Creative Commons
Dixon J. Atkins,

Alan J. Rogers,

Kathryn E. Shaffer

et al.

Tribology Letters, Journal Year: 2025, Volume and Issue: 73(1)

Published: Feb. 4, 2025

Language: Английский

Citations

0
The Intersection between Immune System and Idiopathic Pulmonary Fibrosis—A Concise Review DOI
Hongli Liu,

Huachun Cui,

Gang Liu

et al.

Deleted Journal, Journal Year: 2025, Volume and Issue: 3(1), P. 10004 - 10004

Published: Jan. 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.

Language: Английский

Citations

0
Tropomodulin1 Regulates the Biomechanical Changes in Macrophages Induced by Matrix Stiffness DOI Creative Commons
Yajun Meng,

Amannisa Tuersuntuoheti,

S. JIANG

et al.

Mechanobiology in Medicine, Journal Year: 2025, Volume and Issue: 3(2), P. 100117 - 100117

Published: Feb. 20, 2025

Language: Английский

Citations

0
Molecular mechanism on autophagy associated cardiovascular dysfunction in Drosophila melanogaster DOI Creative Commons
Wei Zhan, Rong Zhou,

Xinjuan Lei

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 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.

Language: Английский

Citations

0