Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1112591 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR29062900_1.fastq.gz | Fastqsanger.gz | |||
| SRR29062900_2.fastq.gz | Fastqsanger.gz | |||
| SRR29062901_1.fastq.gz | Fastqsanger.gz | |||
| SRR29062901_2.fastq.gz | Fastqsanger.gz |
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Project description:Diabetic wounds require continuous and coordinated modulation of the microenvironment concurrent with tissue regeneration, yet this remains a significant challenge. As a proof of concept, we herein propose to use dimeric copper peptide for diabetic wound treatment. The dimeric copper peptide (D-CuP) was first synthesized and then incorporated into a reactive oxygen species (ROS)-responsive hydrogel matrix to improve therapeutic compliance, culminating in the formulation of G/D-CuP. Compared to monomer copper peptide (CuP), a wound healing agent, D-CuP exhibits multivalency, enhanced biologic stability against proteases and the broad biological activities, such as anti-inflammatory and antioxidative properties, while promoting angiogenesis and fibroblast proliferation and migration. Meanwhile, the hydrogel matrix, exhibiting excellent ROS-scavenging capabilities, has been engineered to an intelligent drug reservoir for wound-responsive release of D-CuP at the wound site while simultaneously attenuating inflammatory responses. Ultimately, the G/D-CuP group demonstrated superior therapeutic efficacy, achieving in 97.2% closure of infected wounds.In this study, we present a proof-of-concept study to optimize the treatment of diabetic wounds. This method integrates a dimeric copper peptide hydrogel (G/D-CuP) to address several critical factors: i) The design and synthesis of the dimeric copper peptide (D-CuP) feature a broad range of targets and enhanced biological activities, such as anti-inflammatory and antioxidative properties, while promoting angiogenesis and fibroblast proliferation and migration; ii) Utilizing the steric hindrance conferred by dimerization reduces protease access to the active site and significantly improving stability against proteases; iii) A ROS-responsive hydrogel matrix has been synthesized, exhibiting superior ROS-scavenging capabilities, functioning as an intelligent drug reservoir that enables the controlled release of D-CuP at the wound interface while simultaneously attenuating inflammatory responses in the microenvironment; iv) G/D-CuP possesses outstanding deformability and spreadability, allowing it to adapt to any wound shape; v) The synthesis and preparation process of G/D-CuP are straightforward and cost-effective, making it highly promising for clinical translation. This multifunctional treatment platform is anticipated to accommodate the complex and dynamic biological processes involved in diabetic wound healing, thereby significantly improving the overall efficacy of wound healing treatments.
2025-06-11 | PXD059903 | Pride
Project description:Diabetic infectious wounds treatment is challenging due to insistent wound infections. Treating such complicated pathological diabetic infectious wounds needs to develop multifunctional materials and understand their mechanism. Here, we developed a novel material termed AgNCs-hydrogel, which is a multifunctional DNA hydrogel which dressing by integrating antibacterial silver nanoclusters. AgNCs-hydrogel was used for promoting the regeneration of diabetic infectious wounds in mouses because that it exhibited superior antibacterial activity, satisfactory biocompatibility, and effective ROS-scavenging property. Based on the skin proteomics, we explored the potential mechanism of AgNCs-hydrogel in treating mouse skin wounds. We found that AgNCs-hydrogel can accelerate proliferation and extracellular matrix (ECM) formation. In proteomic level, AgNCs-hydrogel can regulate some key proteins which mainly located in the extracellular exosome, involved in negative regulation of apoptotic process, performed ATP binding for accelerating diabetic infected wound closure. Therefore, this study provided a multifunctional material AgNCs-hydrogel and revealed its potential mechanisms in promoting the regeneration of diabetic infectious wounds.
2023-08-07 | PXD044438 |
Project description:The diabetic wound healing is challenging due to the sabotaged delicate balance of immune regulation via an undetermined pathophysiological mechanism, so it is crucial to decipher multicellular signatures underlying diabetic wound healing and seek therapeutic strategies. Here, we develop a strategy using novel trimethylamine N-oxide (TMAO)-derived zwitterionic hydrogel to promote diabetic wound healing, and explore the multi-cellular ecosystem around zwitterionic hydrogel, mapping out an overview of different cells in the zwitterionic microenvironment using single-cell RNA sequencing. The diverse cellular heterogeneity has been revealed, highlighting the critical role of macrophage and neutrophils in managing diabetic wound healing. It is found that zwitterionic hydrogel can upregulate chemokine-secreted macrophages and downregulate extracellular traps (NETs)-neutrophils and facilitate their interactions compared with polyanionic and polycationic hydrogels, validating the underlying effect of zwitterionic microenvironment on the activation of adaptive immune system. These findings expand our horizons of the sophisticated orchestration of immune systems in zwitterion-directed diabetic wound repair and uncover new strategies of novel immunoregulatory biomaterials.
2025-05-01 | GSE267890 | GEO
Project description:Wound healing is a multi-step process to rapidly restore barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model, but unexpectedly promotes hair follicle regeneration. Neogenic hair follicles expressing Sox-9, CD34 and K15 were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.
2021-05-22 | GSE148037 | GEO
Project description:Chronic and non-healing skin wound is one of grievous complications of diabetes. In this study, we demonstrated a gas (carbon monoxide)-releasing hyaluronic acid hydrogel (i.e. COHAG) in promoting diabetic wound healing. Our results show that the COHAG significantly accelerated the healing process in diabtic rat full-thickness skin defect model, as compared with hydrogel without gas-releasing molecule and untreated group. Single-cell analysis of regenerating skin samples revealed that Cxcl14-overexpressing (Cxcl14+) fibroblast with progenitor properties are abundantly accumulated at the wound site after COHAG therapy.
2023-12-05 | GSE228235 | GEO
Project description:Impaired healing of diabetic wounds causes significant morbidity and mortality. This study aimed to identify novel mechanisms of diabetic wound healing defects and test a therapeutic intervention using diabetic mouse and pig models. We found Smad7 transgene expression in mouse epidermis promoting wound healing in diabetic db/db mice, with reductions in obesity and blood glucose. To isolate effects of Smad7 on wounds, we created a Smad7-based biologic (Tat-PYC-Smad7) that penetrates wound cells. Topical application of Tat-PYC-Smad7 to diabetic pig and mouse wounds accelerated healing compared to controls. RNAseq analysis of mouse wound samples showed reduced TGFβ/NFκB signaling, leading to faster re-epithelialization and better extracellular matrix remodeling. Tat-PYC-Smad7 also attenuated neutrophil degranulation and NETosis by blocking histone 3 citrullination and inhibiting myeloperoxidase activities. Our study reveals that Tat-PYC-Smad7 promotes diabetic wound healing by targeting keratinocytes and neutrophils, providing insight into cellular mechanisms of diabetic wound healing defects targetable by Smad7-based therapy.
2024-08-13 | GSE274513 | GEO
Project description:he dynamic balance of hypoxia and oxidative stress constitutes the oxygen-related microenvironment in injured tissues. Oxygen homeostasis is highly variable; therefore, it is not a therapeutic target for injured tissue repair. We found an enrichment and extensive apoptosis of mesenchymal stem cells (MSCs) infused intravenously in the wound microenvironment with co-existing hypoxia and oxidative stress. Apoptotic bodies (ABs), generated from in situ apoptosis, significantly promotes angiogenesis. We improved the derivation pathway of ABs by simulating oxygen homeostasis in injured tissues, with cobalt chloride-induced hypoxia or hydrogen peroxide-induced oxidative stress in MSCs. Oxygen-related environmental stressed ABs, derived from environments of hypoxic and oxidative stress, were identified and loaded onto hydrogel microspheres for accurate regulation of endothelial cells (ECs) vascularization. These ABs directly targeted ECs; oxidative stress ABs (Oxi-ABs) have a 2.5- and 4-fold higher tube-forming ability than hypoxic and normoxic ABs, respectively. miRNA microarray analysis revealed that different oxygen-stressed ABs deliver similar miRNAs, which leads to the broad upregulation of EC phosphokinase activity. Finally, local delivery of Oxi-ABs-loaded hydrogel microspheres promotes wound healing. Oxi-ABs-loaded hydrogel microspheres achieved controlled AB release, targeting EC by reducing the consumption of early inflammatory cells and adapting to the proliferative phase of wound healing. Thus, the biogenerated apoptotic bodies responding to oxygen-related environmental stress can target ECs to promote vascularization.
2024-01-01 | GSE240216 | GEO
Project description:A whole layer functional regeneration can be achieved by Gel-Fla, which ensures an improved healing effect than commercial dressing approaches. The multi-level and stereo regeneration Gel-Fla system provides a promising strategy in diabetic wound healing.
2024-03-08 | GSE260761 | GEO
Project description:Objective This study aims to investigate the effects of electroacupuncture on chronic wounds associated with diabetes, particularly focusing on its potential mechanisms for enhancing wound healing through the promotion of angiogenesis. While acupuncture has been shown to improve wound healing by enhancing blood supply and vascular regeneration, the therapeutic effects of electroacupuncture in diabetic chronic wounds have not been sufficiently addressed. Methods A diabetic skin ulcer mouse model was established for this study. The effects of electroacupuncture on wound healing were assessed through evaluation of skin healing rates, ELISA assays, and histopathological analyses. Additionally, a tissue transparency three-dimensional imaging technique was utilized to establish a vascular model of wounds on day 10, clarifying the impact of electroacupuncture on angiogenesis during the proliferation phase in diabetic mouse skin wound models. Proteomic analysis was conducted to identify potential targets and mechanisms by which electroacupuncture regulates diabetic wound healing, further validated by immunohistochemistry (IHC) and Western blotting (WB). Results The experimental results demonstrated that electroacupuncture significantly promotes wound healing in diabetic mice, reduces the levels of the pro-inflammatory cytokine IL-6 during the inflammatory phase, decreases inflammatory cell infiltration, and increases collagen synthesis. Proteomic analysis indicated that electroacupuncture may facilitate diabetic wound healing by enhancing endothelial cell proliferation and modulating angiogenic morphogenesis. Furthermore, electroacupuncture was shown to upregulate the expression of CXCL12 and its co-localization with CXCR4, while promoting the phosphorylation of PI3K and AKT, thereby enhancing the expression of VEGF and improving angiogenesis. Three-dimensional tissue transparency imaging provided comprehensive visual evidence of the angiogenic effects induced by electroacupuncture. Conclusion The findings of this study suggest that electroacupuncture activates the PI3K/AKT signaling pathway through the CXCL12/CXCR4 axis to promote vascular regeneration, thereby improving the healing process of diabetic skin wounds in mice.
2024-12-26 | PXD059248 |
Project description:Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the molecular mechanism by which miRNAs influence epithelial regeneration in DK is largely unknown. In this study, we performed miRNA and mRNA sequencing of regenerative corneal epithelium tissue from streptozotocin-induced type 1 diabetic (T1DM) and wild-type mice to screen for differentially expressed miRNAs and mRNAs. Based on regulatory network analysis, miR-223-5p was selected for subsequent experiments and Hpgds was then identified as a direct target gene. MiR-223-5p downregulation significantly promoted diabetic corneal epithelial wound healing and nerve regeneration. However, the beneficial effects of miR-223-5p inhibition were abolished by an Hpgds inhibitor. Furthermore, mechanistic studies demonstrated that miR-223-5p suppression ameliorated inflammation and enhanced cell proliferation signaling in DK. Taken together, our findings revealed that the regulatory role of miR-223-5p in diabetic corneal epithelial and nerve regeneration by mediating inflammatory processes and cell proliferation signaling. And silencing miR-223-5p may contribute to the development of potential therapeutic strategies for DK.
2021-08-23 | GSE180493 | GEO