Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1112591 | ENA |
REPOSITORIES: ENA
Similar Datasets
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: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: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
Project description:Explore the role of these hydrogels in wound healing, this study assessed the effects of both, Dersani Hydrogel with Alginate (DHA) and Dersani Hydrogel (DH), in human skin keratinocytes and fibroblasts gene expression profiles in a wound healing context. Sodium alginate (SA) and culture medium were also included as controls.
2021-07-02 | GSE179187 | GEO
Project description:Unveiling the molecular mechanisms underlying tissue regeneration provides new opportunities to develop treatments for diabetic ulcers and other chronic skin lesions. Here, to gain insight into critical wound response mechanisms regulated by epidermal Nrf2, we micro dissected a ~2.5mm concentric ring around the 10mm wound at 5 days-post-wounding (DPW) and used flow cytometry to isolate wound-associated keratinocytes from Nrf2 +/+ Ker and Nrf2 ∆/∆ Ker mice for bulk RNA-seq. Combining in vivo and ex vivo data with next generation sequencing, we show that Ccl2 secretion by epidermal keratinocytes is directly orchestrated by Nrf2, a prominent transcriptional regulator of tissue regeneration that is activated early after cutaneous injury. Through a unique feedback mechanism, we find that Ccl2 from epidermal keratinocytes not only drives chemotaxis of macrophages into the wound, but also triggers macrophage expression of EGF, which in turn activates basal epidermal keratinocyte proliferation. Notably, we find dysfunctional activation of Nrf2 in epidermal keratinocytes of diabetic mice after wounding, which in part, explains regenerative impairments associated with diabetes. These findings provide mechanistic insight into the critical relationship between keratinocyte-macrophage signaling during tissue regeneration, providing the basis for continued investigation of the therapeutic value of Nrf2.
2020-10-12 | GSE159361 | GEO
Project description:The Janus liposozyme robustly eradicates infections and rapidly promotes wound closure and re-epithelialization on diabetic skin wound infected with methicillin-resistant S. aureus (MRSA). We used single cell RNA sequencing(scRNA-seq) to deep analyse local immune homeostasis manipulated by Janus on skin cells obtained from db/db mice .
2024-01-17 | GSE253098 | GEO