Acetoacetate Ameliorates Skin Fibrosis by Modulating TGF-β1/Smad2/3 Signaling Pathway DOI Creative Commons

Ting Shang,

Linxiao Li,

Xiaohui Miao

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract Skin fibrosis is a progressive pathologic outcome of prolonged healing cutaneous wound which has been well accepted as metabolic disease in recent study. However, the impact ketone body metabolism on development remains largely unknown. Here, we found that was impaired both human scars and bleomycin induced skin fibrogenesis mouse by bioinformatics analysis, further evidenced downregulated expression key modulators including BDH1, OXCT1, ACAT1. With knockdown spontaneous onset normal exacerbation observed. In dermal fibroblasts treated with TGF-β1, OXCT1 improved their phenotype transition to myofibroblasts. Mechanistic studies indicated phosphorylation Smad2/3 signaling markedly suppressed acetoacetate (AcAc) supplementation. More importantly, local administration remarkably alleviated mouse. Thus, our findings underscore therapeutic potential AcAc an alternative intervention for fibrosis.

Language: Английский

pH-Responsive Hydrogel with Dual-crosslinked Network of Polyvinyl Alcohol/Boric Acid for Controlled Release of Salvianolic Acid B: Novel Pro-Regenerative Mechanisms in Scar Inhibition and Wound Healing DOI Creative Commons
Wei Song, Chao Zhang, Li Zhao

et al.

Regenerative Biomaterials, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 1, 2025

Abstract This study investigates a novel pH-responsive hydrogel composed of polyvinyl alcohol (PVA) and boric acid (BA) designed for the controlled release salvianolic B (SAB), addressing critical challenge scar formation skin regeneration. The dual-crosslinked network architecture exhibits remarkable pH sensitivity, enabling it to achieve peak SAB within 48 hours in acidic microenvironment characteristic early-stage wound healing. In vitro assessments demonstrated that PVA-BA-SAB significantly inhibits fibroblast activation mitigates abnormal collagen deposition, effectively preventing excessive formation. Transcriptome sequencing reveals potential role balancing TGF-β Wnt signaling pathways. Furthermore, vivo studies revealed enhanced tissue regeneration, characterized by improved organization increased vascularization, as well promotion mature hair follicle development. hydrogel’s biocompatibility, mechanical robustness adhesive properties were also thoroughly evaluated, confirming its suitability clinical applications. These findings suggest fully exerts excellent characteristics biomaterials maximizes pharmacological effect SAB. Our innovative drug delivery system not only facilitates healing but offers strategic approach minimize scarring. research provides valuable insights into therapeutic strategies effective management repair.

Language: Английский

Citations

2
Leveraging Microneedles for Raised Scar Management DOI Open Access

Zheng-Yun Jin,

Young‐Seong Kim, Joong Yeon Lim

et al.

Polymers, Journal Year: 2025, Volume and Issue: 17(1), P. 108 - 108

Published: Jan. 2, 2025

Disruption of the molecular pathways during physiological wound healing can lead to raised scar formation, characterized by rigid, thick tissue with associated symptoms pain and pruritus. A key mechanical factor in development is excessive tension at site. Recently, microneedles (MNs) have emerged as promising tools for management they engage provide them off-loading from both internal external sources. This review explores mechanisms which physical intervention drug-free MNs alleviates on fibroblasts within tissue, thereby promoting remodeling reducing severity. Additionally, role an efficient cargo delivery system controlled sustained release a wide range therapeutic agents into highlighted. By penetrating facilitate localized drug administration modulate inflammation fibroblastic cell growth. Finally, remaining challenges future perspective field been

Language: Английский

Citations

1
Emerging biomedical technologies for scarless wound healing DOI Creative Commons
Xinyue Cao,

Xiangyi Wu,

Yuanyuan Zhang

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 42, P. 449 - 477

Published: Sept. 11, 2024

Language: Английский

Citations

8
A Multifunctional Nanocomposite Hydrogel Delivery System Based on Dual‐Loaded Liposomes for Scarless Wound Healing DOI
Danlei Xing,

Guoqing Xia,

Xu-Dong Tang

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(28)

Published: July 16, 2024

Abstract Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, scarring places fibroblasts under severe mechanical aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for microenvironment remodeling, incorporating dual‐loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) hepatocyte growth factor (HGF) are encapsulated in hydrophobic hydrophilic layers of liposomes, respectively. The maintains porous nanoarchitecture, demonstrating sustainable THC HGF release enhanced properties biocompatibility. This system effectively promotes cell proliferation angiogenesis attenuates apoptosis. It decreases expression factors by inhibiting high‐mobility group box /receptor advanced glycation end product/NF‐κB (HMGB1/RAGE/NF‐κB)pathway increases macrophage polarization from M1 M2 vitro, controlling responses. exhibits remarkable antioxidant scavenging excess reactive oxygen species free radicals. Most importantly, it prevents scar formation restraining transforming beta (TGF‐β)/Smads pathway that downregulates associated fibrotic factors. demonstrates strong therapeutic effects against inflammation fibrosis rat model with biosafety, advancing development innovative hydrogel‐based delivery strategies clinical scarless therapy.

Language: Английский

Citations

6
Design Strategy of Microneedle Systems for Skin Wound Healing: Based on the Structure of Tips and Therapeutic Methodologies DOI

Wenchao Ji,

Boying Li, Ning Li

et al.

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(7), P. 4254 - 4269

Published: June 12, 2024

The skin, being the largest organ of human body, is susceptible to damage resulting in wounds that are vulnerable pathogenic attacks and fail provide effective protection for internal tissues. Therefore, it crucial expedite wound healing. In recent years, microneedles have garnered significant attention as an innovative drug delivery system owing their noninvasive painless administration, simplified application process, precise control over release, versatile loading capabilities. Consequently, they hold immense potential treatment skin wound. This review presents a comprehensive design strategy microneedle promoting First, process healing characteristics specific elucidated. strategies subsequently presented classified based on structural therapeutic methodologies. Finally, succinct recapitulation previously discussed points prospective analysis provided.

Language: Английский

Citations

4
Expanded taxonomies of human memory DOI Creative Commons
Jason R. Finley

Frontiers in Cognition, Journal Year: 2025, Volume and Issue: 3

Published: Jan. 15, 2025

What is human memory? Evidence from cognitive psychology and neuroscience supports the view that memory composed of multiple subsystems. The influential “modal model” late 1960s proposed a sensory register, short-term store, long-term store. Refinements expansions to this taxonomy followed, including construct working memory, itself with several components, replace earlier simpler ideas memory. Long-term appears also consist subsystems, which can be broadly divided into explicit (declarative) vs. implicit (nondeclarative). Explicit further subdivided episodic semantic, includes subtypes such as procedural priming, classical conditioning, habituation. All above take place in brain, driven by neurons processes potentiation depression. I previously an expanded included external information stored outside individual's social (information other people) technological human-made environment, either low-tech paper, or high-tech computers). In manuscript, propose even taxonomies based on my transmission across time. second expansion encompasses numerous biological systems beside immune system, genetics (DNA epigenetics), traces past elsewhere body (skin, hair, modification, nails, bones teeth, muscles movement, voice, digestion excretion, blood, reproductive systems, fat, lungs, body-based numerical representation). third distinguishes between individual collective (shared group), revisits using lens adds natural Fruitful insights are possible considering these traditional (e.g., encoding, storage, retrieval, forgetting). explore parallels, distinctions, interplays.

Language: Английский

Citations

0
The Role of Fibroblasts in Chronic Inflammatory and Proliferative Skin Diseases DOI

Rui Zang,

C. Xu,

Fan Zhu

et al.

Experimental Dermatology, Journal Year: 2025, Volume and Issue: 34(2)

Published: Feb. 1, 2025

ABSTRACT Fibroblasts (FBs) are crucial mesenchymal cells that preserve the skin's natural structure and physiological processes. They can build dense connective tissue by remodelling extracellular matrix (ECM) control immunological activity secreting cytokines. This indicates development of chronic inflammatory proliferative skin disorders is significantly influenced fibroblasts. In order to provide new ideas for clinical research treatment with a clearer perspective, this study thoroughly compiles involvement fibroblasts in various diseases such as psoriasis, hypertrophic scar (HS), keloid, atopic dermatitis (AD), oral lichen planus (OLP), eczema, rosacea.

Language: Английский

Citations

0
Assessing the Predictive Accuracy of ChatGPT-Based Image Analysis in Forecasting Long-Term Scar Characteristics from 3-Month Assessments – a pilot study DOI

Antoinette T Nguyen,

R. Li,

Robert D. Galiano

et al.

Journal of Plastic Reconstructive & Aesthetic Surgery, Journal Year: 2025, Volume and Issue: 104, P. 200 - 208

Published: March 13, 2025

Language: Английский

Citations

0
Biology and Pathophysiology of Placenta Accreta Spectrum Disorder DOI
Yalda Afshar, Lior Kashani Ligumsky, Helena C. Bartels

et al.

Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Placenta accreta spectrum (PAS) disorders present a significant clinical challenge, characterized by abnormal placental adherence to the uterine wall secondary scarring. With rising global cesarean delivery rates, incidence of this iatrogenic disorder has increased, underscoring critical need for an understanding its pathophysiology inform management and prevention strategies. Normal placentation depends on tightly regulated extravillous trophoblast invasion into decidua, spiral artery remodeling, interactions with extracellular matrix, immune modulation. Uterine scarring disrupts balance, creating environment deficient in key regulatory signals required coordinated implantation decidualization. In PAS, loss inhibitory decidual cues boundary limits permits unrestrained environment. Dysregulated signaling, along inflammatory milieu scarred tissues, exacerbates development. Current prenatal imaging focuses appearance excessive fibrinoid deposition, matrix incomplete transformation as surrogates PAS risk stratification. Emerging single-cell RNA sequencing proteomic profiling offer insights biomarkers pathways that enable targeted interventions. Preventive efforts should prioritize reducing rates limit Advances regenerative medicine bioengineering, including matrix–modulating biomaterials, growth factor therapies, antifibrotic interventions, hold promise improving scar healing risk. This review bridges foundational science application, emphasizing importance underlying biology make difference detecting, treating, preventing PAS. Addressing drivers is maternal neonatal outcomes increasingly prevalent condition.

Language: Английский

Citations

0
Blockade of Sialylation with Decrease in Polysialic Acid Levels Counteracts Transforming Growth Factor β1-Induced Skin Fibroblast-to-Myofibroblast Transition DOI Creative Commons
Bianca Saveria Fioretto, Irene Rosa, Alessia Tani

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(12), P. 1067 - 1067

Published: June 19, 2024

Aberrant sialylation with overexpression of the homopolymeric glycan polysialic acid (polySia) was recently reported in fibroblasts from fibrotic skin lesions. Yet, whether such a rise polySia levels or general may be functionally implicated profibrotic activation and their transition to myofibroblasts remains unknown. Therefore, we herein explored inhibition could interfere process fibroblast-to-myofibroblast induced by master mediator transforming growth factor β1 (TGFβ1). Adult human were pretreated competitive pan-sialyltransferase inhibitor 3-Fax-peracetyl-Neu5Ac (3-Fax) before stimulation recombinant TGFβ1, then analyzed for expression, cell viability, proliferation, migratory ability, acquisition myofibroblast-like morphofunctional features. Skin fibroblast TGFβ1 resulted polySia, which effectively blunted 3-Fax pre-administration. Pretreatment efficiently lessened TGFβ1-induced migration, changes morphology, phenotypic functional differentiation into myofibroblasts, as testified significant reduction FAP, ACTA2, COL1A1, COL1A2, FN1 gene α-smooth muscle actin, N-cadherin, FN-EDA protein levels, well reduced contractile capability. Moreover, pre-administered displayed decrease Smad3-dependent canonical signaling. Collectively, our vitro findings demonstrate first time that aberrant increased has role suggest sialyltransferase might offer new therapeutic opportunities against fibrosis.

Language: Английский

Citations

2