Pub Date : 2025-10-24eCollection Date: 2025-01-01DOI: 10.1093/burnst/tkaf065
Children constitute a key population for scar prevention and treatment because of the unique features of their skin's physiological structure and psychosomatic growth. Currently, most approaches to pediatric scar management are formulated with reference to adult-related consensuses and guidelines, which fail to fully account for the specific characteristics of pediatric scars and their distinct needs in relation to growth and development. As a result, there are controversies regarding specific prevention and treatment strategies. To address this limitation, the Chinese Burn Association brought together domestic and international experts from disciplines relevant to the field of scar prevention and treatment. Guided by evidence-based medical evidence, drawing on domestic and international literature, and integrating the clinical experience of specialist physicians, the branch first conducted consultations on clinical issues and then organized multiple rounds of expert meetings for discussions. Eventually, the Clinical practice guideline for pediatric scar prevention and treatment (2025 edition) was developed. Focusing on 10 key aspects of pediatric scar prevention and treatment, the guideline formulates 20 recommendation opinions. It also elaborates on the remaining controversial issues in this field, aiming to provide scientific guidance for the entire process of prevention, treatment, and rehabilitation of scars in children aged 1-14 years.
{"title":"Clinical practice guideline for pediatric scar prevention and treatment (2025 edition).","authors":"","doi":"10.1093/burnst/tkaf065","DOIUrl":"10.1093/burnst/tkaf065","url":null,"abstract":"<p><p>Children constitute a key population for scar prevention and treatment because of the unique features of their skin's physiological structure and psychosomatic growth. Currently, most approaches to pediatric scar management are formulated with reference to adult-related consensuses and guidelines, which fail to fully account for the specific characteristics of pediatric scars and their distinct needs in relation to growth and development. As a result, there are controversies regarding specific prevention and treatment strategies. To address this limitation, the Chinese Burn Association brought together domestic and international experts from disciplines relevant to the field of scar prevention and treatment. Guided by evidence-based medical evidence, drawing on domestic and international literature, and integrating the clinical experience of specialist physicians, the branch first conducted consultations on clinical issues and then organized multiple rounds of expert meetings for discussions. Eventually, the <i>Clinical practice guideline for pediatric scar prevention and treatment (2025 edition)</i> was developed. Focusing on 10 key aspects of pediatric scar prevention and treatment, the guideline formulates 20 recommendation opinions. It also elaborates on the remaining controversial issues in this field, aiming to provide scientific guidance for the entire process of prevention, treatment, and rehabilitation of scars in children aged 1-14 years.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"13 ","pages":"tkaf065"},"PeriodicalIF":9.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12632194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23eCollection Date: 2026-01-01DOI: 10.1093/burnst/tkaf068
Aline Yen Ling Wang, Ana Elena Aviña, Yen-Yu Liu, Huang-Kai Kao
Research shows that the microbiome of the skin is present as an active contributor to wound healing processes by moving past its historical infection-related function. The review investigates how commensal and probiotic bacteria affect immunomodulation while accelerating epithelial growth, together with tissue repair processes. Researchers use modern methods to link immunological concepts with material science along with synthetic biological techniques to study engineered probiotics which transform current wound treatments. The research study represents an extensive integration of recent findings concerning probiotic-mediated immunomodulatory operations and engineered approaches that improve probiotic delivery systems and their performance during skin wound healing procedures. Recent genetically engineered Lactobacillus reuteri strains that express chemokines like CXCL12 have been found to promote wound healing to an accelerated rate in animal models, and pre-clinical phases of clinical trials in the setting of diabetic foot ulcers (DFU) has demonstrated safety and therapeutic potential. Simultaneously, another live biotherapeutic product has been validated in terms of regenerative and immunomodulatory properties in animal models and in a clinical trial, a multi-cytokine-integrated strain of Lactococcus cremoris secreting FGF-2, IL-4, and CSF-1 promoted faster wound healing in diabetic mice and healed 83% of subjects in a Phase I DFU study. The range of probiotic therapies for trauma care expands due to advancements in probiotic delivery using materials and membrane vesicles derived from probiotics. This review builds a detailed framework that connects core immune functions with modern engineering methods for developing smart wound healing systems that combine engineered probiotics with bioresponsive materials and real-time monitoring systems. Engineered probiotics promise to become an alternative strategy for treating chronic wounds and infection-related complications that currently create significant medical problems.
{"title":"Microbial allies in skin trauma recovery: from immune modulation to engineered probiotic therapeutics.","authors":"Aline Yen Ling Wang, Ana Elena Aviña, Yen-Yu Liu, Huang-Kai Kao","doi":"10.1093/burnst/tkaf068","DOIUrl":"10.1093/burnst/tkaf068","url":null,"abstract":"<p><p>Research shows that the microbiome of the skin is present as an active contributor to wound healing processes by moving past its historical infection-related function. The review investigates how commensal and probiotic bacteria affect immunomodulation while accelerating epithelial growth, together with tissue repair processes. Researchers use modern methods to link immunological concepts with material science along with synthetic biological techniques to study engineered probiotics which transform current wound treatments. The research study represents an extensive integration of recent findings concerning probiotic-mediated immunomodulatory operations and engineered approaches that improve probiotic delivery systems and their performance during skin wound healing procedures. Recent genetically engineered <i>Lactobacillus reuteri</i> strains that express chemokines like CXCL12 have been found to promote wound healing to an accelerated rate in animal models, and pre-clinical phases of clinical trials in the setting of diabetic foot ulcers (DFU) has demonstrated safety and therapeutic potential. Simultaneously, another live biotherapeutic product has been validated in terms of regenerative and immunomodulatory properties in animal models and in a clinical trial, a multi-cytokine-integrated strain of <i>Lactococcus cremoris</i> secreting FGF-2, IL-4, and CSF-1 promoted faster wound healing in diabetic mice and healed 83% of subjects in a Phase I DFU study. The range of probiotic therapies for trauma care expands due to advancements in probiotic delivery using materials and membrane vesicles derived from probiotics. This review builds a detailed framework that connects core immune functions with modern engineering methods for developing smart wound healing systems that combine engineered probiotics with bioresponsive materials and real-time monitoring systems. Engineered probiotics promise to become an alternative strategy for treating chronic wounds and infection-related complications that currently create significant medical problems.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 ","pages":"tkaf068"},"PeriodicalIF":9.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Following spinal cord injury (SCI), mechanical trauma and an inflammatory microenvironment activate the PKCδ-TRPA1 pathway, resulting in calcium overload within neurons and subsequently inducing endoplasmic reticulum stress-mediated neuronal apoptosis. The mechanisms and therapeutic potential of electroacupuncture (EA) in the treatment of SCI have yet to be fully elucidated. This study aimed to explore the causes of neuronal Ca2+ overload post-SCI and to investigate the neuroprotective and regenerative mechanisms of EA in an SCI mouse model. Methods C57BL6 mice were randomly divided into a Sham group, an SCI group and an SCI + EA group. The Basso Mouse Scale (BMS), motor-evoked potential (MEP) and movement videos of the mice were captured, and DeepLabCut was used to analyse the recovery of motor function. Western blotting was used to detect the protein levels of related indicators. Immunofluorescence staining was used to analyse the cellular localization and fluorescence intensity of each indicator. Hematoxylin and Eosin(H&E) staining and Nissl staining were used for histological evaluation. EA treatment resulted in higher BMS scores; increased ankle, knee and hip mobility; and improved hindlimb support in the EA group. Results PKCδ and TRPA1 protein expression was upregulated after SCI, and neuronal calcium ion overload occurred, leading to neuronal Endoplasmic reticulum(ER) stress-induced apoptosis. After EA treatment, inflammatory microenvironment-related indicators were downregulated, which inhibited the activation of calcium channels by PKCδ-TRPA1, reduced ER stress-induced apoptosis caused by calcium overload in neurons, and protected neurons from secondary injury. EA increases the expression of neurotrophic factors and promotes nerve regeneration, and we found that EA treatment promotes axonal elongation by stabilizing microtubules. Conclusions According to our findings, (1) mechanical injury and the inflammatory microenvironment after SCI activate PKCδ-TRPA1, which is important for neuronal ER stress and apoptosis caused by neuronal calcium overload. (2) EA treatment reduces the expression of PKCδ-TRPA1 as well as the ER stress and apoptosis caused by neuronal calcium overload. (3) EA promoted neurogenesis and axonal regeneration by promoting the secretion of neurotrophic factors and promoted axon elongation by stabilizing microtubules, thus promoting the recovery of motor function in SCI mice.
{"title":"Electroacupuncture Reduces Calcium Influx and Inhibits Endoplasmic Reticulum Stress by Inhibiting the PKCδ-TRPA1 Pathway to Promote Motor Function Recovery After Spinal Cord Injury","authors":"Yihui Zhang, Chenhe Liang, Zhiyang Huang, Yusi Hu, Yujun Mo, Shaoxia Ning, Ziyi Li, Yungang Wu, Jiaxin Zhang, Xiaokun Li, Zhouguang Wang","doi":"10.1093/burnst/tkaf066","DOIUrl":"https://doi.org/10.1093/burnst/tkaf066","url":null,"abstract":"Background Following spinal cord injury (SCI), mechanical trauma and an inflammatory microenvironment activate the PKCδ-TRPA1 pathway, resulting in calcium overload within neurons and subsequently inducing endoplasmic reticulum stress-mediated neuronal apoptosis. The mechanisms and therapeutic potential of electroacupuncture (EA) in the treatment of SCI have yet to be fully elucidated. This study aimed to explore the causes of neuronal Ca2+ overload post-SCI and to investigate the neuroprotective and regenerative mechanisms of EA in an SCI mouse model. Methods C57BL6 mice were randomly divided into a Sham group, an SCI group and an SCI + EA group. The Basso Mouse Scale (BMS), motor-evoked potential (MEP) and movement videos of the mice were captured, and DeepLabCut was used to analyse the recovery of motor function. Western blotting was used to detect the protein levels of related indicators. Immunofluorescence staining was used to analyse the cellular localization and fluorescence intensity of each indicator. Hematoxylin and Eosin(H&E) staining and Nissl staining were used for histological evaluation. EA treatment resulted in higher BMS scores; increased ankle, knee and hip mobility; and improved hindlimb support in the EA group. Results PKCδ and TRPA1 protein expression was upregulated after SCI, and neuronal calcium ion overload occurred, leading to neuronal Endoplasmic reticulum(ER) stress-induced apoptosis. After EA treatment, inflammatory microenvironment-related indicators were downregulated, which inhibited the activation of calcium channels by PKCδ-TRPA1, reduced ER stress-induced apoptosis caused by calcium overload in neurons, and protected neurons from secondary injury. EA increases the expression of neurotrophic factors and promotes nerve regeneration, and we found that EA treatment promotes axonal elongation by stabilizing microtubules. Conclusions According to our findings, (1) mechanical injury and the inflammatory microenvironment after SCI activate PKCδ-TRPA1, which is important for neuronal ER stress and apoptosis caused by neuronal calcium overload. (2) EA treatment reduces the expression of PKCδ-TRPA1 as well as the ER stress and apoptosis caused by neuronal calcium overload. (3) EA promoted neurogenesis and axonal regeneration by promoting the secretion of neurotrophic factors and promoted axon elongation by stabilizing microtubules, thus promoting the recovery of motor function in SCI mice.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"79 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background The efficacy of exosomes from adipose-derived stem cells (ADSC-exos) in accelerating diabetic wound healing is limited due to the inflammation and hypoxia of the wound. Thus, the design of microenvironment-responsive ADSC-exos sustained-release hydrogel dressings that maximize the biological role of exosomes and alleviate the inflammation of diabetic wound is essential. Methods In this study, we prepared a glucose/pH dual-responsive multifunctional hydrogel loaded with ADSC-exos based on dynamic dual cross-linking via Schiff bases and phenylboronic esters, with the aim of achieving intelligent release of ADSC-exos in response to the acidic and high-glucose-concentration pathological microenvironment in diabetic wounds. Results This hydrogel showed swelling and degradation characteristics in high glucose/low pH environment, resulting in an increased release of ADSC-exos. The antimicrobial activity and improved mechanical properties of the hydrogel were achieved via the introduction of a second dynamic cross-linking network involving 4-arm SH-poly (ethylene glycol) and Ag+. In a chronic diabetic full-thickness skin wound model, compared with non-responsive ADSC-exos-loaded hydrogels, the dual-responsive hydrogel ameliorated tissue inflammation and increased angiogenesis by promoting the conversion of macrophages to the anti-inflammatory M2 phenotype, showing an increased healing rate. The underlying mechanism revealed that dual-responsive release of ADSC-exos improves the wound microenvironment by inhibiting the Notch/NF-κB/NLRP3 signaling pathway. Conclusion We successfully developed a dual-responsive hydrogel delivery system that responds efficiently to the high-glucose and acidic microenvironment via Notch/NF-κB/NLRP3 signaling pathway, thereby promoting healing of chronic diabetic wounds.
{"title":"Multiple dynamic crosslinked multifunctional hydrogels with glucose/pH dual-responsive ADSC-exosomes-releasing for diabetic wound healing","authors":"Yue Zhang, Meng Li, Shijie Song, Fenghui Hei, Shaoyang Ma, Jiao Cao, Baolin Guo, Dahai Hu","doi":"10.1093/burnst/tkaf059","DOIUrl":"https://doi.org/10.1093/burnst/tkaf059","url":null,"abstract":"Background The efficacy of exosomes from adipose-derived stem cells (ADSC-exos) in accelerating diabetic wound healing is limited due to the inflammation and hypoxia of the wound. Thus, the design of microenvironment-responsive ADSC-exos sustained-release hydrogel dressings that maximize the biological role of exosomes and alleviate the inflammation of diabetic wound is essential. Methods In this study, we prepared a glucose/pH dual-responsive multifunctional hydrogel loaded with ADSC-exos based on dynamic dual cross-linking via Schiff bases and phenylboronic esters, with the aim of achieving intelligent release of ADSC-exos in response to the acidic and high-glucose-concentration pathological microenvironment in diabetic wounds. Results This hydrogel showed swelling and degradation characteristics in high glucose/low pH environment, resulting in an increased release of ADSC-exos. The antimicrobial activity and improved mechanical properties of the hydrogel were achieved via the introduction of a second dynamic cross-linking network involving 4-arm SH-poly (ethylene glycol) and Ag+. In a chronic diabetic full-thickness skin wound model, compared with non-responsive ADSC-exos-loaded hydrogels, the dual-responsive hydrogel ameliorated tissue inflammation and increased angiogenesis by promoting the conversion of macrophages to the anti-inflammatory M2 phenotype, showing an increased healing rate. The underlying mechanism revealed that dual-responsive release of ADSC-exos improves the wound microenvironment by inhibiting the Notch/NF-κB/NLRP3 signaling pathway. Conclusion We successfully developed a dual-responsive hydrogel delivery system that responds efficiently to the high-glucose and acidic microenvironment via Notch/NF-κB/NLRP3 signaling pathway, thereby promoting healing of chronic diabetic wounds.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"102 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Keloids are a common skin fibroproliferative disease that can result in severe aesthetic and functional concerns. Pruritus and pain are the most prevalent clinical manifestations of keloids. Schwann cells (SCs) variation and neuropathy within keloids contribute to these uncomfortable sensations; however the underlying mechanisms remain unclear. Objectives To explore the potential role of fibroblasts (FBs) and SCs in pruritic and pain keloids. Methods The activity of FBs and SCs was investigated using single-cell RNA sequencing (scRNA-seq) data of keloids. These bioinformatics analysis results were validated through in vitro cell culture, clinical samples, and in vivo experiments. The selected molecule was confirmed to be correlated with pain and itch and was subsequently used to treat cells in order to investigate its role in keloids. The in vivo inhibition assay was performed to evaluate its therapeutic potential. Results Our scRNA-seq analysis identified specific types of FBs and SCs were present in higher proportions in keloids and exhibited neurogenesis-related functions. Upon conducting an interaction analysis of these two cell types, we identified a critical molecule, Midkine (MDK), which is positively correlated with the patients’ pain and itching levels. Besides, MDK treatment facilitated the proliferation of SCs and their transition to a repairing phenotype, resulting in neuronal axonogenesis. This activation of repairing SCs promoted the release of substance P from nerve fibers, leading to clinical symptoms of pain and pruritus in keloid patients. Targeting MDK effectively reduces abnormal Schwann cell proliferation and subsequently inhibits the secretion of neuropeptides that trigger pain and pruritus. Conclusion Our study uncovered the interaction between FBs and SCs in the development of keloidal pain and pruritus, offering a novel therapeutic strategy to alleviate the distressing symptoms of keloids.
{"title":"Single cell deciphering of pruritic keloids: the interaction between fibroblasts and Schwann cells through the Midkine signaling","authors":"En Yang, Ruoqing Xu, Liying Tu, Hanrui Zhang, Shenying Luo, Hsin Liang, Yunhan Liu, Shuchen Gu, Yixuan Zhao, Xin Huang, Tao Zan","doi":"10.1093/burnst/tkaf057","DOIUrl":"https://doi.org/10.1093/burnst/tkaf057","url":null,"abstract":"Background Keloids are a common skin fibroproliferative disease that can result in severe aesthetic and functional concerns. Pruritus and pain are the most prevalent clinical manifestations of keloids. Schwann cells (SCs) variation and neuropathy within keloids contribute to these uncomfortable sensations; however the underlying mechanisms remain unclear. Objectives To explore the potential role of fibroblasts (FBs) and SCs in pruritic and pain keloids. Methods The activity of FBs and SCs was investigated using single-cell RNA sequencing (scRNA-seq) data of keloids. These bioinformatics analysis results were validated through in vitro cell culture, clinical samples, and in vivo experiments. The selected molecule was confirmed to be correlated with pain and itch and was subsequently used to treat cells in order to investigate its role in keloids. The in vivo inhibition assay was performed to evaluate its therapeutic potential. Results Our scRNA-seq analysis identified specific types of FBs and SCs were present in higher proportions in keloids and exhibited neurogenesis-related functions. Upon conducting an interaction analysis of these two cell types, we identified a critical molecule, Midkine (MDK), which is positively correlated with the patients’ pain and itching levels. Besides, MDK treatment facilitated the proliferation of SCs and their transition to a repairing phenotype, resulting in neuronal axonogenesis. This activation of repairing SCs promoted the release of substance P from nerve fibers, leading to clinical symptoms of pain and pruritus in keloid patients. Targeting MDK effectively reduces abnormal Schwann cell proliferation and subsequently inhibits the secretion of neuropeptides that trigger pain and pruritus. Conclusion Our study uncovered the interaction between FBs and SCs in the development of keloidal pain and pruritus, offering a novel therapeutic strategy to alleviate the distressing symptoms of keloids.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"28 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pu Fang, Shuai Li, Zong-Qing Lu, Dun-Lin Xia, Meng-meng Xu, Jingjing Pan, Lin Fu, Geng-Yun Sun, Qing-Hai You
Background: Circulating lactate is associated with poor prognosis in sepsis-induced acute lung injury (S-ALI). However, it remains unclear whether microvascular dysfunction, a hallmark of S-ALI, is related to circulating lactate levels and what the underlying mechanisms are. The aim of this study was to investigate the role and mechanisms of lactate in pulmonary microvascular dysfunction in S-ALI. Methods: The effects of lactate on pulmonary microvascular function were assessed in a septic mouse model. Primary mouse pulmonary microvascular endothelial cells (MPMVECs) were isolated to evaluate the impact of lactate on MPMVEC permeability. Transcriptomic sequencing was employed to investigate the involvement of lactate in regulating MPMVEC ferroptosis, and the results were validated by in vivo and in vitro experiments. Histone lactylation was identified as a regulator of lipid peroxidation and iron homeostasis dysregulation in lactate-induced ferroptosis in MPMVECs. Gain- and loss-of-function approaches were used to assess the role of histone lactylation in regulating ferroptosis and pulmonary microvascular dysfunction. Correlations between serum lactate and ferroptosis levels and their associations with patient prognosis were investigated in patients with sepsis-associated acute respiratory distress syndrome (S-ARDS). Results: The mouse serum lactate level reached a peak at 18 hours after caecal ligation and puncture surgery. Elevated lactate levels during sepsis promoted ferroptosis in PMVECs, leading to increased pulmonary vascular permeability and exacerbation of ALI. Mechanistically, lactate increased the lactylation of histone H3 at K18 (H3K18la), which promoted ACSL4 transcription in MPMVECs, resulting in excessive lipid peroxidation. Additionally, elevated H3K18la promoted LC3 transcription and indirectly upregulated NCOA4 expression through the transcription factor GATA2, facilitating ferritinophagy. Serum lactate levels were significantly correlated with ferroptosis levels in S-ARDS patients, and both were associated with poor patient prognosis. Conclusion: This study revealed a critical role for high lactate-derived histone lactylation in PMVEC ferroptosis and the progression of ALI during sepsis, providing new insights and potential therapeutic mechanisms.
{"title":"Histone Lactylation Exacerbates Acute Lung Injury in Septic Mice by Promoting Ferroptosis in Pulmonary Microvascular Endothelial Cells","authors":"Pu Fang, Shuai Li, Zong-Qing Lu, Dun-Lin Xia, Meng-meng Xu, Jingjing Pan, Lin Fu, Geng-Yun Sun, Qing-Hai You","doi":"10.1093/burnst/tkaf056","DOIUrl":"https://doi.org/10.1093/burnst/tkaf056","url":null,"abstract":"Background: Circulating lactate is associated with poor prognosis in sepsis-induced acute lung injury (S-ALI). However, it remains unclear whether microvascular dysfunction, a hallmark of S-ALI, is related to circulating lactate levels and what the underlying mechanisms are. The aim of this study was to investigate the role and mechanisms of lactate in pulmonary microvascular dysfunction in S-ALI. Methods: The effects of lactate on pulmonary microvascular function were assessed in a septic mouse model. Primary mouse pulmonary microvascular endothelial cells (MPMVECs) were isolated to evaluate the impact of lactate on MPMVEC permeability. Transcriptomic sequencing was employed to investigate the involvement of lactate in regulating MPMVEC ferroptosis, and the results were validated by in vivo and in vitro experiments. Histone lactylation was identified as a regulator of lipid peroxidation and iron homeostasis dysregulation in lactate-induced ferroptosis in MPMVECs. Gain- and loss-of-function approaches were used to assess the role of histone lactylation in regulating ferroptosis and pulmonary microvascular dysfunction. Correlations between serum lactate and ferroptosis levels and their associations with patient prognosis were investigated in patients with sepsis-associated acute respiratory distress syndrome (S-ARDS). Results: The mouse serum lactate level reached a peak at 18 hours after caecal ligation and puncture surgery. Elevated lactate levels during sepsis promoted ferroptosis in PMVECs, leading to increased pulmonary vascular permeability and exacerbation of ALI. Mechanistically, lactate increased the lactylation of histone H3 at K18 (H3K18la), which promoted ACSL4 transcription in MPMVECs, resulting in excessive lipid peroxidation. Additionally, elevated H3K18la promoted LC3 transcription and indirectly upregulated NCOA4 expression through the transcription factor GATA2, facilitating ferritinophagy. Serum lactate levels were significantly correlated with ferroptosis levels in S-ARDS patients, and both were associated with poor patient prognosis. Conclusion: This study revealed a critical role for high lactate-derived histone lactylation in PMVEC ferroptosis and the progression of ALI during sepsis, providing new insights and potential therapeutic mechanisms.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"38 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shunli Rui, Fugang Xiao, Qin Li, Mengling Yang, Linrui Dai, Shiyan Yu, Xiaoshi Zhang, Xiaoyan Jiang, Seungkuk Ahn, Wenxin Wang, David G Armstrong, Hongyan Wang, Guangbin Huang, Wuquan Deng
Background Diabetic foot ulcer (DFU) is a common and debilitating complication of diabetes, often leading to delayed wound healing. The peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating cellular metabolism and promoting angiogenesis. However, the mechanisms by which PPARs activation enhances wound healing, particularly in diabetic conditions, remain insufficiently understood. Methods Differentially expressed genes in DFU wounds and normal skin tissues were identified using the GEO database. PPARs expression in DFU neovascularization was validated by qRT-PCR, immunofluorescence, and western blotting. In vivo, diabetic mice treated with PPARs agonists (Chiglitazar) underwent wound healing assessment, including collagen deposition and angiogenesis. In vitro, high-glucose-induced endothelial cell models were used to evaluate PPARs activation effects on cell migration, tube formation, and mitochondrial function. Whole transcriptome sequencing and mitochondrial analysis were performed to explore the underlying mechanisms, particularly the sonic hedgehog (SHH) -mitochondrial axis. Results PPARs expression was significantly downregulated in DFU tissues (p < 0.05), and PPARs activation in diabetic mice enhanced wound healing, collagen deposition, granulation tissue proliferation, and angiogenesis (p < 0.05). In vitro, PPAR activation protected endothelial cells, promoting VEGF-A and CD31 expression, reducing apoptosis, and enhancing cell migration and tube formation (p < 0.05). Mechanistically, PPARs activated mitochondrial oxidative phosphorylation (OXPHOS) and membrane function through the SHH signaling pathway. SHH gene silencing reversed the effects of PPARs activation on mitochondrial function and angiogenesis. Conclusions PPARs signaling plays a critical role in DFU healing, with its inhibition linked to vascular dysfunction. Activation of the PPARs/SHH -mitochondrial axis significantly enhances endothelial cell metabolism and angiogenesis. This study provides insights into the molecular mechanisms of diabetic wound healing and supports the clinical potential of PPARs agonists for DFU treatment.
{"title":"PPARs Mediated Diabetic Wound Healing Regulates Endothelial Cells Mitochondrial Function via Sonic Hedgehog Signaling","authors":"Shunli Rui, Fugang Xiao, Qin Li, Mengling Yang, Linrui Dai, Shiyan Yu, Xiaoshi Zhang, Xiaoyan Jiang, Seungkuk Ahn, Wenxin Wang, David G Armstrong, Hongyan Wang, Guangbin Huang, Wuquan Deng","doi":"10.1093/burnst/tkaf063","DOIUrl":"https://doi.org/10.1093/burnst/tkaf063","url":null,"abstract":"Background Diabetic foot ulcer (DFU) is a common and debilitating complication of diabetes, often leading to delayed wound healing. The peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating cellular metabolism and promoting angiogenesis. However, the mechanisms by which PPARs activation enhances wound healing, particularly in diabetic conditions, remain insufficiently understood. Methods Differentially expressed genes in DFU wounds and normal skin tissues were identified using the GEO database. PPARs expression in DFU neovascularization was validated by qRT-PCR, immunofluorescence, and western blotting. In vivo, diabetic mice treated with PPARs agonists (Chiglitazar) underwent wound healing assessment, including collagen deposition and angiogenesis. In vitro, high-glucose-induced endothelial cell models were used to evaluate PPARs activation effects on cell migration, tube formation, and mitochondrial function. Whole transcriptome sequencing and mitochondrial analysis were performed to explore the underlying mechanisms, particularly the sonic hedgehog (SHH) -mitochondrial axis. Results PPARs expression was significantly downregulated in DFU tissues (p &lt; 0.05), and PPARs activation in diabetic mice enhanced wound healing, collagen deposition, granulation tissue proliferation, and angiogenesis (p &lt; 0.05). In vitro, PPAR activation protected endothelial cells, promoting VEGF-A and CD31 expression, reducing apoptosis, and enhancing cell migration and tube formation (p &lt; 0.05). Mechanistically, PPARs activated mitochondrial oxidative phosphorylation (OXPHOS) and membrane function through the SHH signaling pathway. SHH gene silencing reversed the effects of PPARs activation on mitochondrial function and angiogenesis. Conclusions PPARs signaling plays a critical role in DFU healing, with its inhibition linked to vascular dysfunction. Activation of the PPARs/SHH -mitochondrial axis significantly enhances endothelial cell metabolism and angiogenesis. This study provides insights into the molecular mechanisms of diabetic wound healing and supports the clinical potential of PPARs agonists for DFU treatment.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"100 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Sepsis-associated acute lung injury (ALI) is driven by endothelial barrier dysfunction and endothelial–mesenchymal transition (EndoMT), mediated by TGF-β1/SMAD3 signaling. Despite the therapeutic potential of SMAD3, current inhibitors face limitations. As endogenous small molecules that are closely related to physiological regulatory processes, miRNAs have more potential research value for regulating SMAD3. Methods Screening multiple databases revealed that miR-23b-3p was the sole miRNA targeting SMAD3. LPS-stimulated HUVECs and cecal ligation/puncture (CLP) mice were used to model sepsis. Lentivirus was used to construct stable strains. The functional performance and mechanism were verified by key techniques, including dual-luciferase assays, rescue experiments, RT–qPCR/Western blotting, monocyte adhesion/permeability assays, and histopathology. Results In LPS-stimulated HUVECs, miR-23b-3p downregulation correlated with TGF-β1/SMAD3 activation, EndoMT progression, and barrier disruption. miR-23b-3p overexpression reversed these effects by restoring the expression of junctional proteins and suppressing the expression of mesenchymal markers. ChIRP-qPCR, RNA-pull-down, and dual-luciferase assays confirmed the direct miR-23b-3p—SMAD3 3’UTR interaction. Rescue experiments demonstrated that miR-23b-3p counteracts TGF-β1/SMAD3 hyperactivation. In CLP mice, intratracheal agomiR-23b-3p attenuated lung injury, normalized alveolar architecture, and reduced vascular leakage by suppressing endothelial Smad3 upregulation. Conclusion miR-23b-3p is a SMAD3-targeting regulator that inhibits EndoMT and repairs endothelial barrier integrity. Mechanistically, miR-23b-3p preserves endothelial homeostasis via SMAD3-dependent EndoMT inhibition. This study provides mechanistic insights and a miRNA-based therapeutic strategy for sepsis-induced ALI.
{"title":"Rescuing Endothelial Barrier Dysfunction in Sepsis: miR-23b-3p Antagonizes SMAD3-Mediated EndoMT and Vascular Hyperpermeability","authors":"Luofeng Jiang, Wei Zhang, Heng He, Xirui Tong, Futing Shu, Jiezhi Lin, Lu Yang, Hongchao Huang, Wenzhang Liu, Tianyi Liu, Yingying Liu, Pengfei Luo, Yongjun Zheng, Zhaofan Xia","doi":"10.1093/burnst/tkaf062","DOIUrl":"https://doi.org/10.1093/burnst/tkaf062","url":null,"abstract":"Background Sepsis-associated acute lung injury (ALI) is driven by endothelial barrier dysfunction and endothelial–mesenchymal transition (EndoMT), mediated by TGF-β1/SMAD3 signaling. Despite the therapeutic potential of SMAD3, current inhibitors face limitations. As endogenous small molecules that are closely related to physiological regulatory processes, miRNAs have more potential research value for regulating SMAD3. Methods Screening multiple databases revealed that miR-23b-3p was the sole miRNA targeting SMAD3. LPS-stimulated HUVECs and cecal ligation/puncture (CLP) mice were used to model sepsis. Lentivirus was used to construct stable strains. The functional performance and mechanism were verified by key techniques, including dual-luciferase assays, rescue experiments, RT–qPCR/Western blotting, monocyte adhesion/permeability assays, and histopathology. Results In LPS-stimulated HUVECs, miR-23b-3p downregulation correlated with TGF-β1/SMAD3 activation, EndoMT progression, and barrier disruption. miR-23b-3p overexpression reversed these effects by restoring the expression of junctional proteins and suppressing the expression of mesenchymal markers. ChIRP-qPCR, RNA-pull-down, and dual-luciferase assays confirmed the direct miR-23b-3p—SMAD3 3’UTR interaction. Rescue experiments demonstrated that miR-23b-3p counteracts TGF-β1/SMAD3 hyperactivation. In CLP mice, intratracheal agomiR-23b-3p attenuated lung injury, normalized alveolar architecture, and reduced vascular leakage by suppressing endothelial Smad3 upregulation. Conclusion miR-23b-3p is a SMAD3-targeting regulator that inhibits EndoMT and repairs endothelial barrier integrity. Mechanistically, miR-23b-3p preserves endothelial homeostasis via SMAD3-dependent EndoMT inhibition. This study provides mechanistic insights and a miRNA-based therapeutic strategy for sepsis-induced ALI.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"25 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01eCollection Date: 2026-01-01DOI: 10.1093/burnst/tkaf061
Marina Moreno-Martínez, Artur Dalfó-Pibernat, Josep Vidal-Alaball
Background: Burns and wounds cause significant physical and psychological distress, with pain being a major barrier to recovery. Traditional pharmacological methods for pain management carry risks such as side effects and dependency. Virtual reality has emerged as a non-invasive, distraction-based technique that may reduce pain perception during wound care by modulating sensory input.
Methods: This systematic review and meta-analysis, conducted following PRISMA guidelines and registered in PROSPERO (CRD420251005004), assessed the effectiveness of virtual reality in managing pain during wound and burn care. A comprehensive search of PubMed, Web of Science, Scopus, and Cochrane Library was conducted in March 2025. Eligible studies included randomized controlled trials comparing virtual reality interventions to standard care or other distraction techniques in patients with active wounds or burns. Data on pain outcomes, as well as physiological indicators, were extracted. Meta-analysis was performed using a random-effects model and Hedges' g as the effect size estimator. The analysis was performed with SPSS version 29 and the risk of bias was assessed using the RoB 2.0 tool.
Results: Eleven studies (n = 936 participants) were included, with diverse wound types (burns, surgical, limb injuries) and virtual reality setups, predominantly immersive. The overall pooled effect showed a statistically significant reduction in pain using virtual reality (g = -1.528; 95% CI: -2.259 to -0.797; p < 0.001), indicating a moderate-to-large effect. Subgroup analysis revealed that virtual reality was most effective in children (g = -2.348), followed by adolescents (g = -0.538), while adults showed a non-significant effect (g = -1.453). High heterogeneity (I2 = 95.5%) was explained by age group differences and sensitivity analysis. No significant publication bias was detected.
Conclusions: Virtual reality appears to be a promising tool for reducing procedural pain, particularly in children with wounds or burns. Its efficacy in adolescents is moderate, while evidence in adults remains inconclusive. Given its non-pharmacological nature and potential to improve patient experience, virtual reality warrants broader implementation and further age-specific research in wound care settings.
背景：烧伤和伤口造成严重的生理和心理困扰，疼痛是恢复的主要障碍。传统的疼痛管理药理学方法存在副作用和依赖性等风险。虚拟现实已经成为一种非侵入性的、基于分心的技术，可以通过调节感觉输入来减少伤口护理过程中的疼痛感。方法：本系统综述和荟萃分析遵循PRISMA指南并在PROSPERO注册（CRD420251005004），评估虚拟现实在处理伤口和烧伤护理期间疼痛方面的有效性。我们于2025年3月对PubMed、Web of Science、Scopus和Cochrane Library进行了全面的检索。符合条件的研究包括随机对照试验，比较虚拟现实干预与标准护理或其他分散注意力技术对活跃伤口或烧伤患者的影响。提取疼痛结局和生理指标的数据。meta分析采用随机效应模型，Hedges’g作为效应量估计量。采用SPSS version 29进行分析，使用RoB 2.0工具评估偏倚风险。结果：纳入了11项研究（n = 936名参与者），涉及不同类型的伤口（烧伤、手术、肢体损伤）和虚拟现实设置，主要是沉浸式的。总体综合效应显示，使用虚拟现实后疼痛的减轻具有统计学意义（g = -1.528; 95% CI: -2.259至-0.797;p = 95.5%），这可以用年龄组差异和敏感性分析来解释。未发现显著的发表偏倚。结论：虚拟现实似乎是一个很有前途的工具，以减少程序性疼痛，特别是对儿童的伤口或烧伤。它对青少年的疗效中等，而对成人的疗效尚无定论。鉴于其非药物性质和改善患者体验的潜力，虚拟现实需要在伤口护理环境中更广泛的实施和进一步的年龄特异性研究。
{"title":"Virtual reality as a pain reduction method in burn and wound healing: a systematic review and meta-analysis.","authors":"Marina Moreno-Martínez, Artur Dalfó-Pibernat, Josep Vidal-Alaball","doi":"10.1093/burnst/tkaf061","DOIUrl":"10.1093/burnst/tkaf061","url":null,"abstract":"<p><strong>Background: </strong>Burns and wounds cause significant physical and psychological distress, with pain being a major barrier to recovery. Traditional pharmacological methods for pain management carry risks such as side effects and dependency. Virtual reality has emerged as a non-invasive, distraction-based technique that may reduce pain perception during wound care by modulating sensory input.</p><p><strong>Methods: </strong>This systematic review and meta-analysis, conducted following PRISMA guidelines and registered in PROSPERO (CRD420251005004), assessed the effectiveness of virtual reality in managing pain during wound and burn care. A comprehensive search of PubMed, Web of Science, Scopus, and Cochrane Library was conducted in March 2025. Eligible studies included randomized controlled trials comparing virtual reality interventions to standard care or other distraction techniques in patients with active wounds or burns. Data on pain outcomes, as well as physiological indicators, were extracted. Meta-analysis was performed using a random-effects model and Hedges' g as the effect size estimator. The analysis was performed with SPSS version 29 and the risk of bias was assessed using the RoB 2.0 tool.</p><p><strong>Results: </strong>Eleven studies (n = 936 participants) were included, with diverse wound types (burns, surgical, limb injuries) and virtual reality setups, predominantly immersive. The overall pooled effect showed a statistically significant reduction in pain using virtual reality (g = -1.528; 95% CI: -2.259 to -0.797; p < 0.001), indicating a moderate-to-large effect. Subgroup analysis revealed that virtual reality was most effective in children (g = -2.348), followed by adolescents (g = -0.538), while adults showed a non-significant effect (g = -1.453). High heterogeneity (I<sup>2</sup> = 95.5%) was explained by age group differences and sensitivity analysis. No significant publication bias was detected.</p><p><strong>Conclusions: </strong>Virtual reality appears to be a promising tool for reducing procedural pain, particularly in children with wounds or burns. Its efficacy in adolescents is moderate, while evidence in adults remains inconclusive. Given its non-pharmacological nature and potential to improve patient experience, virtual reality warrants broader implementation and further age-specific research in wound care settings.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 ","pages":"tkaf061"},"PeriodicalIF":9.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12888808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Chronic wounds, particularly diabetic ulcers, impose significant health and economic burdens globally because of their complex pathology and the limited availability of therapeutic approaches. Multiple microRNAs (miRNAs) play crucial roles in regulating biological processes in wound healing. However, single-miRNA therapies may not fully overcome multifaceted barriers of impaired wound repair. Efforts to discover more effective wound therapies continue unabated. Methods In this study, we developed a microRNA cocktail that targets multiple critical phases of the wound healing: inflammation, re-epithelialization, granulation tissue formation and angiogenesis. This therapeutic cocktail includes locked nucleic acid (LNA)-modified mimics of miR-19b-3p, miR-132-3p, and miR-31-5p, along with an inhibitor of miR-92a-3p, which are delivered via in vivo-jetPEI as the carrier, addressing the multifaceted nature of wound repair mechanisms. The wound healing efficacy of the cocktail were systematically evaluated in mouse models of acute and chronic wounds. Results Local application of the miRNA cocktail to wounds markedly enhanced acute wound healing in wild-type mice, outperforming the effects of the individual miRNAs. Moreover, the miRNA cocktail accelerated diabetic wound healing by orchestrating coordinated cellular responses at the wound site and significantly decreasing inflammatory cytokine expression and CD68+ macrophage migration while promoting re-epithelialization, angiogenesis and granulation tissue formation. Notably, the cocktail also facilitated nerve regeneration in the wound area at day 30 post-injury. Conclusions Our findings suggest that this miRNA cocktail has potential therapeutic value for revitalizing the healing process in chronic wounds. Therefore, further investigations in controlled clinical trials are warranted to confirm the efficacy and applicability of this miRNA cocktail in a clinical setting.
{"title":"A miRNA cocktail orchestrates coordinated cellular responses to promote diabetic wound healing","authors":"Yejing Huang, Liping Zhu, Jiating Wang, Ling Pan, Yong Yang, Dongqing Li","doi":"10.1093/burnst/tkaf060","DOIUrl":"https://doi.org/10.1093/burnst/tkaf060","url":null,"abstract":"Background Chronic wounds, particularly diabetic ulcers, impose significant health and economic burdens globally because of their complex pathology and the limited availability of therapeutic approaches. Multiple microRNAs (miRNAs) play crucial roles in regulating biological processes in wound healing. However, single-miRNA therapies may not fully overcome multifaceted barriers of impaired wound repair. Efforts to discover more effective wound therapies continue unabated. Methods In this study, we developed a microRNA cocktail that targets multiple critical phases of the wound healing: inflammation, re-epithelialization, granulation tissue formation and angiogenesis. This therapeutic cocktail includes locked nucleic acid (LNA)-modified mimics of miR-19b-3p, miR-132-3p, and miR-31-5p, along with an inhibitor of miR-92a-3p, which are delivered via in vivo-jetPEI as the carrier, addressing the multifaceted nature of wound repair mechanisms. The wound healing efficacy of the cocktail were systematically evaluated in mouse models of acute and chronic wounds. Results Local application of the miRNA cocktail to wounds markedly enhanced acute wound healing in wild-type mice, outperforming the effects of the individual miRNAs. Moreover, the miRNA cocktail accelerated diabetic wound healing by orchestrating coordinated cellular responses at the wound site and significantly decreasing inflammatory cytokine expression and CD68+ macrophage migration while promoting re-epithelialization, angiogenesis and granulation tissue formation. Notably, the cocktail also facilitated nerve regeneration in the wound area at day 30 post-injury. Conclusions Our findings suggest that this miRNA cocktail has potential therapeutic value for revitalizing the healing process in chronic wounds. Therefore, further investigations in controlled clinical trials are warranted to confirm the efficacy and applicability of this miRNA cocktail in a clinical setting.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"10 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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