Signal execution modes emerge in biochemical reaction networks calibrated to experimental data DOI Creative Commons

Oscar O Ortega,

Mustafa Ozen, Blake A. Wilson

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109989 - 109989

Published: May 16, 2024

Mathematical models of biomolecular networks are commonly used to study cellular processes; however, their usefulness explain and predict dynamic behaviors is often questioned due the unclear relationship between parameter uncertainty network dynamics. In this work, we introduce PyDyNo (Python analysis biochemical networks), a non-equilibrium reaction-flux based identify dominant reaction paths within calibrated experimental data. We first show, in simplified apoptosis execution model, that despite thousands vectors with equally good fits data, our framework identifies differences these sets outputs three modes, which exhibit varying sensitivity perturbations. then apply methodology JAK2/STAT5 colony-forming unit-erythroid (CFU-E) cells provide previously unrecognized mechanistic explanation for survival responses CFU-E cell population would have been impossible deduce traditional protein-concentration analyses.

Language: Английский

Supercritical Fluid‐Processed Multifunctional Hybrid Decellularized Extracellular Matrix with Chitosan Hydrogel for Improving Photoaged Dermis Microenvironment DOI Creative Commons
Seol‐Ha Jeong, Jimmy J.H. Kang,

Ki‐Myo Kim

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Abstract To address the demand for reconstructive procedures in extensive subcutaneous tissue defects and significant dermis matrix loss, vascularized adipose regeneration is essential maintaining volume after material degradation. Accordingly, a double‐crosslinked hydrogel that combines polyethylene glycol (PEG)‐crosslinked carboxymethyl chitosan (CMC) with hybrid decellularized extracellular (dECM) developed. The dECM, sourced from porcine cardiac tissues, processed using supercritical fluid technique (scCO 2 ‐EtOH) retains 1.5–5‐fold more angiogenic adipogenic cytokines than traditional methods. This dECM‐based filler demonstrates excellent physical properties injectability, injection forces being significantly less crosslinked hyaluronic acid (HA) fillers. Upon incubation at 37 °C, storage modulus of fillers increases substantially, eventually enhancing their moldability additional crosslinking thermosensitive nature collagen. Assessments UVB‐induced photoaging mouse model indicate maintains superior shape stability, durability, supports regeneration, reduces inflammation, enhances VEGF expression ECM maturation effectively compared other These promising results suggest can serve as highly effective multifunctional solution injectable regenerative medical applications well‐suited potential clinical trials.

Language: Английский

Citations

0
Potential Targets Related to Skin Aging: Based on eQTL and GWAS Datasets DOI Creative Commons
Hanping Shi, Xianwei Cao

Clinical Cosmetic and Investigational Dermatology, Journal Year: 2025, Volume and Issue: Volume 18, P. 677 - 686

Published: March 1, 2025

The aging of skin has important impact on various systems, and certain (SG) markers can not only help with early diagnosis, but also provide new ideas for pathophysiological research treatment strategies. To identify target genes related to SG through bioinformatics technology anti-aging. Differential expression (DEGs) were screened transcriptome information from GEO datasets (GSE85358 GSE670988). Based eQTL GWAS datasets, Mendelian Randomization (MR) analysis was applied associations between gene SG. Then, (AS-IGs) obtained based above two steps, functional pathway analyses performed explore the potential mechanisms AS-IGs in Finally, CIBERSORT evaluation used assess infiltration immune cells Seven selected intersection 612 DEGs 399 genes. enrichment results showed there 60 GO terms may involved process SG, like fatty-acyl-CoA metabolic process, while KEGG pathways identified mainly fatty acid metabolism, energy generation, inflammation regulation. that NK resting main infiltrating cells. play roles body. These molecules involve multiple systems body, such as function, neuroendocrine function.

Language: Английский

Citations

0
Pyrroloquinoline Quinone Reprograms the Single‐Cell Landscape of Immune Aging in Hematopoietic Immune System DOI Creative Commons
Xiuxing Liu, Chun Zhang, Jianjie Lv

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

ABSTRACT Aging is an inevitable biological process, driven in part by increased oxidative stress, which accelerates cellular damage and contributes to immune system dysfunction. Therefore, targeting stress has emerged as a potential strategy. Pyrroloquinoline quinone (PQQ), potent antioxidant, demonstrated significant efficacy reducing modulating responses, making it promising therapeutic candidate. In this study, we investigated the effects of aging on hematopoietic (HIS) through single‐cell RNA sequencing (scRNA‐seq) spleen bone marrow cells murine models. Our results revealed widespread age‐related inflammation within cell populations. Notably, long‐term PQQ supplementation improved physiological parameters reduced blood inflammatory factors levels aged mice. Subsequent scRNA‐seq analysis that effectively across various HIS types reversed aging‐related phenotypes, such responses immunosenescence. Additionally, aging‐induced disrupted signaling restored homeostasis, particularly B stem (HSCs). Importantly, identified critical molecular targets, including ASPP1, mediates PQQ's anti‐apoptotic cells, Yy1 CD62L, were upregulated restore HSCs self‐renewal differentiation potential. Furthermore, machine learning program experimental validation senolytic senomorphic vivo vitro. These findings underscore not only mitigating but also restoring homeostasis promoting regeneration, highlighting its addressing improving function.

Language: Английский

Citations

0
Aging, senescence, and cutaneous wound healing—a complex relationship DOI Creative Commons
Steven O’Reilly, Ewa Markiewicz, Olusola Idowu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 17, 2024

Cutaneous wound healing is a complex multi-step process that highly controlled, ensuring efficient repair to damaged tissue and restoring architecture. Multiple cell types play critical role in healing, perturbations this can lead non-healing wounds or scarring fibrosis. Thus, the tightly regulated controlled. Cellular senescence defined as irreversible cycle arrest associated with various phenotypic changes metabolic alterations coupled secretory program. Its at least acute setting, appears help promote appropriate mechanisms leading complete restoration of Opposing chronic where it either Given two opposing outcomes settings, has led disparate views on healing. This review aims consolidate knowledge aging examining nuances roles attempts evaluate modulation

Language: Английский

Citations

2
Signal execution modes emerge in biochemical reaction networks calibrated to experimental data DOI Creative Commons

Oscar O Ortega,

Mustafa Ozen, Blake A. Wilson

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109989 - 109989

Published: May 16, 2024

Mathematical models of biomolecular networks are commonly used to study cellular processes; however, their usefulness explain and predict dynamic behaviors is often questioned due the unclear relationship between parameter uncertainty network dynamics. In this work, we introduce PyDyNo (Python analysis biochemical networks), a non-equilibrium reaction-flux based identify dominant reaction paths within calibrated experimental data. We first show, in simplified apoptosis execution model, that despite thousands vectors with equally good fits data, our framework identifies differences these sets outputs three modes, which exhibit varying sensitivity perturbations. then apply methodology JAK2/STAT5 colony-forming unit-erythroid (CFU-E) cells provide previously unrecognized mechanistic explanation for survival responses CFU-E cell population would have been impossible deduce traditional protein-concentration analyses.

Language: Английский

Citations

1