Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1283934 | ENA |
REPOSITORIES: ENA
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Project description:Background and objectives: Current clinical interventions lack effective strategies to arrest temporomandibular joint osteoarthritis (TMJOA) progression. Emerging evidence highlights the therapeutic potential of microRNAs (miRNAs) in osteoarthritis (OA) management, though critical challenges persist regarding delivery efficiency, including unsatisfactory cellular uptake, immunogenicity, and structural instability of miRNA-based therapeutics. Methods and results: Considering the powerful editability of tetrahedral framework nucleic acids (tFNAs) for gene delivery, we engineered a novel nanoscale gene delivery system using tetrahedral framework nucleic acids functionalized with miR-143-3p (tFNAs-143). Through comprehensive in vivo modeling of TMJOA destabilization and in vitro simulation of IL-1β-induced inflammatory microenvironments, we systematically investigated the therapeutic efficacy and molecular mechanisms underlying OA pathophysiology of tFNAs-143. Our results demonstrated that tFNAs-143 exhibited excellent cellular internalization in chondrocytes and effectively mitigated TMJOA progression by impeding ferritinophagy-mediated ferroptosis. Conclusions: This study advanced miRNA delivery technology for TMJOA therapy, deepened the insights into TMJOA pathogenesis, and proposed a promising nano therapeutic strategy for developing targeted TMJOA therapies.
2026-01-21 | GSE303194 | GEO
Project description:Chronic wounds, characterized by delayed healing and persistent inflammation, represent a major clinical burden with limited effective therapies. Inspired by the stereoselective interactions in biological systems, we developed an L-chiral hydrogel composed of self-assembled helical nanofibers from L-histidine derivatives, which preferentially enriches lactate to promote wound repair. Compared to D-chiral and racemic hydrogels, the L-chiral hydrogel significantly accelerated wound closure in rat models, achieving nearly 90% healing by day 14 and reducing healing time to 16-17 days. Transcriptomic and metabolomic analyses revealed enhanced wound response pathways and elevated lactate levels in the L-chiral group. Mechanistically, enriched lactate induced K57 lactylation of RNF123, mediated by AARS1, altering RNF123 conformation and weakening its binding to UBAC1. This modification enhanced ubiquitination and processing of NF-κB p105 into p50, inhibiting the NF-κB pathway and promoting angiogenesis via enhanced endothelial cell migration, tube formation, and sprouting. Rescue experiments with lactate inhibitor Oxamate and exogenous lactate confirmed the lactate-dependent mechanism. This study not only demonstrates a drug-free chiral biomaterial for efficient wound healing but also unveils the molecular role of lactate-mediated lactylation in mechanoregulating inflammation and vascularization, offering new insights for regenerative medicine.
2025-10-17 | GSE308113 | GEO
Project description:Infections of burn wounds, especially those caused by Pseudomonas aeruginosa, could trigger sepsis or septic shock, which is the main cause of death after burn injury. Compared with traditional saline-wet-to-dry dressings, negative pressure wound therapy (NPWT) is more effective for the prevention and treatment of wound infections. However, the mechanism by which NPWT controls infection and accelerates wound healing remains unclear. Accordingly, in this study, the molecular mechanisms underlying the effects of NPWT were explored using a murine model of P. aeruginosa-infected burn wounds. NPWT significantly reduced P. aeruginosa levels in wounds, enhanced blood flow, and promoted wound healing. Additionally, NPWT markedly alleviated wound inflammation and increased the expression of wound healing–related molecules. Recent evidence points to a role of circular RNAs (circRNAs) in wound healing; hence, whole-transcriptome sequencing of wound tissues from NPWT and control groups was performed to evaluate circRNA expression profiles.
2022-01-14 | GSE193428 | GEO
Project description:Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a “band-aid” to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving “compression hemostasis” for deep tissue bleeding sites. The DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrated the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.
2024-07-01 | GSE268849 | GEO
Project description:Thermal injury incites inflammatory responses that often transcend the local environment and lead to structural deficiencies in skin that give way to scar formation. We hypothesized that extensive perturbations within burned skin following thermal insult and during subsequent events of wound repair induce vast alterations in gene expression that likely serve as a wound and systemic healing deterrent. A high-throughput microarray experiment was designed to analyze genetic expression patterns and identify potential genes to target for therapeutic augmentation or silencing. The study compares gene expression from burn wound margins at various times following thermal injury to expression observed in normal skin. Utilizing this design, we report that the totality of gene expression alterations is indeed enormous. Further, we observed that the differential expression of many inflammatory and immune response genes appear to be continually up-regulated in burn wound margins seven days or more after initial thermal insult. As it is well established that the inflammatory process must abate for wound healing to proceed, the finding of ongoing local inflammation is cause for further investigation. To our knowledge, this is the first report of the gene expression alterations induced by thermal injury of human skin. As such, it provides a wealth of data to mine with the ultimate goal of better understanding the local pathophysiologic changes at the site of thermal injury that not only affect wound healing capacity, but may also contribute to systemic derangements within the burn patient. Keywords: time course, disease state analysis The study compares gene expression from burn wound margins at various times following thermal injury to expression observed in normal skin. All skin specimens were obtained in the operating room within minutes of being removed from the patient. Burn specimens were taken from wound margins. Harvested tissue at the burn wound margin maximized the capture of viable cells from the multiple lineages important to the healing process and minimized the inclusion of non-viable cells destroyed by full-thickness injury. After isolation, RNA samples were pooled equally by mass as to contain RNA from 5 tissue specimens for each array replicate.
2010-05-22 | E-GEOD-8056 | biostudies-arrayexpress
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: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: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:Burn wound blister fluid is a valuable matrix for understanding the biological pathways associated with burn injury. In this study, 152 blister fluid samples collected from paediatric burn wounds at two different hospitals were analysed using mass spectrometry proteomic techniques. The protein abundance profile at different days post-burn indicated that there were more proteins associated with cellular damage/repair in the first 24 hours, whereas after this point there were more proteins associated with antimicrobial defence and inflammation. The inflammatory proteins persisted at a high level in the blister fluid for more than 7 days. This may indicate that removal of burn blisters prior to two days post-burn is optimal to prevent excessive or prolonged inflammation in the wound environment. Additionally, many proteins associated with the neutrophil extracellular trap (NET) pathway were increased post-burn, further implicating NETs in the post-burn inflammatory response. NET inhibitors may therefore be a potential treatment to reduce post-burn inflammation and coagulation pathology and enhance burn wound healing outcomes.
2024-03-04 | PXD050003 | Pride