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

Cancer-intrinsic Cxcl5 orchestrates a global metabolic reprogramming for resistance to oxidative cell death in 3D DOI Creative Commons

Ramin Seo,

Arvie Camille V. de Guzman, Sunghyouk Park

et al.

Cell Death and Differentiation, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Pancreatic ductal adenocarcinoma is characterized by a three-dimensional (3D) tumor microenvironment devoid of oxygen and nutrients but enriched in extracellular matrix, which acts as physical chemical barrier. In 3D, cancer cells reprogram their metabolic pathways ways that help them survive hostile conditions. However, little known about the phenotypes 3D intrinsic cues modulate them. We found Cxcl5 deletion restricted pancreatic growth spheroid-in-Matrigel culture system without affecting cell 2D culture. impaired 3D-specific global reprogramming, resistance to hypoxia-induced death, upregulation Hif1α Myc. Overexpression Myc, however, effectively restored culture-induced reconfiguration, growth, redox homeostasis, mitochondrial function Cxcl5-/- cells, reducing ferroptosis. also patients with higher expression hypoxia metabolism-related genes whose well-correlated CXCL5 generally have poorer prognosis. Together, our findings identify an unanticipated role orchestrating reprogramming required for energy biomass maintenance restricts oxidative death. Thus, results provide rationale targeting promising therapeutic strategy.

Language: Английский

Citations

0
Cascade Nanozyme-Loaded Sprayable Hydrogels for Fibroblast Rejuvenation and Diabetic Wound Regeneration DOI
Xinyi Zhang, Yuan Yang, Jianyu Su

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

Multifunctional composite wound dressings hold significant promise for diabetic healing. However, the detrimental role of advanced glycation end-products (AGEs)-reactive oxygen species (ROS) cycle in impeding repair remains underexplored. To disrupt this pathological cycle, zeolitic imidazolate framework-8 (ZIF-8) encapsulated cerium dioxide (CeO2) and adsorbed glucose oxidase (GOx) nanozyme particles ((ZIF-8@CeO2)@GOx, zcg) were loaded into a methacrylic anhydride-modified gelatin (GelMA) hydrogel to form sprayable dressing, zcg/GelMA (zcgG). Physicochemical characterization revealed that GOx catalyzes oxidation, triggering ZIF-8 acid-mediated decomposition release zinc ions CeO2 nanoparticles, thereby enabling cascade depletion, antioxidant, antiglycation functions. In vitro antimicrobial cytotoxicity experiments optimized zcg concentration GelMA. Under oxidative hyperglycemic culture conditions, we validated mechanism blocking AGEs-ROS restoring fibroblast mitochondrial membrane potential, subsequently suppressing cellular senescence. bacterial-infected rat skin model, zcgG group demonstrated substantially reduced inflammatory levels, 68% decrease AGEs, 1.9-fold increase collagen deposition compared blank controls. Within 2 weeks, achieved complete closure, while control retained 28% initial area. This work provides preliminary evidence feasibility using nanozymes break promote

Language: Английский

Citations

0
Macrophage response to fibrin structure mediated by Tgm2-dependent mitochondrial mechanosensing DOI

Bicong Gao,

Haifeng Ni,

Junhong Lai

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 50, P. 382 - 395

Published: April 22, 2025

Language: Английский

Citations

0
Nanotube Topography Inhibits NLRP3 Inflammasome Activation by Reducing Microtubule Glutamylation DOI Creative Commons

Dingqiang Mo,

Wenxue Zhang,

Hengji Jia

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101838 - 101838

Published: May 1, 2025

Language: Английский

Citations

0
New Insights Into the Pathophysiology of Structural Bioprosthetic Valve Degeneration DOI
Marine Sallé, Guillaume Guimbretière, Claire Toquet

et al.

Published: Jan. 1, 2025

Biological heart valves (BHVs) are currently the main prosthetic substitute used to treat patients with severe valvular diseases. Unlike mechanical valves, BHVs provide better hemodynamic profile and lower thrombogenicity. However, their durability remains one of concerns in field. Structural bioprosthetic valve degeneration (SVD) is a progressive phenomenon occurring early postimplantation characterized by fibro-calcification BHV leaflets, which leads failure over ∼10 years. SVD an unpreventable untreatable condition all BHV. The pathophysiological mechanisms leading development progression remain largely unknown. understanding these will valuable data improve via preventive treatments and/or newly engineered biological tissues. In this review, we contemporary overview complex interrelated SVD. We discussed relevant studies fields, addressing role (i) biomaterial structure manufacturing processes, (ii) active cell-mediated fibro-calcific (iii) residual immunogenicity animal-derived biomaterial, (iv) subclinical thrombosis,

Language: Английский

Citations

0
Exploring therapy for tooth eruption disturbances from the perspective of ECM-macrophage DOI

Han Qin,

Jun Cai

Medical Hypotheses, Journal Year: 2025, Volume and Issue: unknown, P. 111662 - 111662

Published: May 1, 2025

Language: Английский

Citations

0
Mild Hyperthermia Accelerates Bone Repair by Dynamically Regulating iNOS/Arg1 Balance in the Early Stage DOI Creative Commons
Jinhui Zhao, Yiping Luo, Lei Zhang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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.

Language: Английский

Citations

3
Manipulating immune activity of macrophages: a materials and mechanics perspective DOI
Abigail J. Clevenger, Aakanksha Jha, Erika Moore

et al.

Trends in biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

Citations

2
Mechanoimmune-Driven Backpack Sustains Dendritic Cell Maturation for Synergistic Tumor Radiotherapy DOI

Huan Yu,

Zhan Liu,

Haoxiang Guo

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(34), P. 23741 - 23756

Published: Aug. 19, 2024

Cell backpacks present significant potential in both therapeutic and diagnostic applications, making it essential to further explore their interactions with host cells. Current evidence indicates that can induce sustained immune responses. Our original objective was incorporate a model antigen into the promote dendritic cell maturation facilitate presentation, thereby inducing However, we unexpectedly discovered antigen-loaded empty demonstrated comparable abilities maturation, resulting nearly identical potency T-cell proliferation. mechanistic studies suggest attachment of induces mechanical forces on cells via opening PIEZO1 ion channel. This interaction leads remodeling intracellular cytoskeleton facilitates production type I interferons by Consequently, mechano-immune-driven backpacks, when combined radiotherapy, robust antitumor effect. research presents an avenue for leveraging mechanotransduction enhance combination immunotherapeutic strategies, potentially leading groundbreaking advancements field.

Language: Английский

Citations

2
The role of the cytoskeleton in fibrotic diseases DOI Creative Commons

Caoyuan Niu,

Yanan Hu, Kai Xu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 24, 2024

Fibrosis is the process whereby cells at a damaged site are transformed into fibrotic tissue, comprising fibroblasts and an extracellular matrix rich in collagen fibronectin, following damage to organs or tissues that exceeds their repair capacity. Depending on affected tissues, fibrosis can be classified types such as pulmonary fibrosis, hepatic renal cardiac fibrosis. The primary pathological features of diseases include recurrent normal abnormal activation fibroblasts, leading excessive deposition intercellular spaces. However, etiology certain specific remains unclear. Recent research increasingly suggests cytoskeleton plays significant role diseases, with structural changes potentially influencing progression organ This review examines cytoskeletal remodeling its impact transformation tissue during offering important insights therapeutic strategies for diseases.

Language: Английский

Citations

2