Sen Tong, Tuo Zhang, Ning Chen, Jing-peng Liu, Shu-ting Wei, Tian-zhen Hua, Yu Duan, Bing Sun, Ning Dong, Yao Wu, Xiao-mei Zhu, Yong-ming Yao
Background Sepsis is a life-threatening condition characterized by profound immune dysregulation and organ dysfunction. The functional impairment of dendritic cells (DCs) in septic patients is well-documented and contributes significantly to sepsis-induced immunosuppression; yet the underlying mechanisms remain poorly understood. Tripartite motif 13 (TRIM13) has been identified as an immune regulator with predominantly suppressive effects. Here, we aimed to investigate the potential role of TRIM13 restriction in promoting the DC-mediated immune response during sepsis. Methods Splenic DCs were isolated from wild-type (WT) and DC-specific Trim13 conditional knockout (Trim13 cKO) mice post-cecum ligation and puncture (CLP). These cells were subsequently analyzed by proteomics, immunoblotting, flow cytometry, and transmission electron microscopy (TEM). DC2.4 cells were infected with either Trim13 shRNA or a Trim13 overexpression lentiviral vector and treated with different pharmacological inhibitors. Protein interactions were examined via Coimmunoprecipitation (Co-IP) and confocal microscopy. Cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), and organ lesions were assessed through H&E staining, immunohistochemistry (IHC) for CD45, and TUNEL assays. Results TRIM13 expression was rapidly upregulated in DCs following septic challenge. Deletion of TRIM13 in DCs disrupted the endoplasmic reticulum (ER)-associated degradation (ERAD) and ER-selective autophagy (ER-phagy)-mediated degradation of the stimulator of interferon genes (STING), leading to sustained STING activation and enhanced DC function. STING signaling promoted the p-IRF3 nuclear translocation, NLRP3 inflammasome priming, and transient DC pyroptosis, thereby exacerbating hyperinflammation in the acute phase of sepsis. Over the longer term, prolonged STING signaling inhibited DCs from adopting the immunosuppressive phenotype and promoting the DC-mediated immune response. Ultimately, TRIM13 deficiency in DCs ameliorated sepsis-induced immunosuppression, preserved organ function in the late phase of sepsis, and reduced overall mortality in septic mice. Conclusions TRIM13 acts as a key negative regulator of DC function during sepsis. Restricting TRIM13 sustains DC immunostimulatory property, counteracts sepsis-induced immunosuppression, and improves survival outcomes. These findings highlight TRIM13 as a potential therapeutic target for sepsis management.
{"title":"TRIM13 orchestrates ERAD and ER-phagy to modulate dendritic cell-mediated immune responses in sepsis","authors":"Sen Tong, Tuo Zhang, Ning Chen, Jing-peng Liu, Shu-ting Wei, Tian-zhen Hua, Yu Duan, Bing Sun, Ning Dong, Yao Wu, Xiao-mei Zhu, Yong-ming Yao","doi":"10.1093/burnst/tkaf077","DOIUrl":"https://doi.org/10.1093/burnst/tkaf077","url":null,"abstract":"Background Sepsis is a life-threatening condition characterized by profound immune dysregulation and organ dysfunction. The functional impairment of dendritic cells (DCs) in septic patients is well-documented and contributes significantly to sepsis-induced immunosuppression; yet the underlying mechanisms remain poorly understood. Tripartite motif 13 (TRIM13) has been identified as an immune regulator with predominantly suppressive effects. Here, we aimed to investigate the potential role of TRIM13 restriction in promoting the DC-mediated immune response during sepsis. Methods Splenic DCs were isolated from wild-type (WT) and DC-specific Trim13 conditional knockout (Trim13 cKO) mice post-cecum ligation and puncture (CLP). These cells were subsequently analyzed by proteomics, immunoblotting, flow cytometry, and transmission electron microscopy (TEM). DC2.4 cells were infected with either Trim13 shRNA or a Trim13 overexpression lentiviral vector and treated with different pharmacological inhibitors. Protein interactions were examined via Coimmunoprecipitation (Co-IP) and confocal microscopy. Cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), and organ lesions were assessed through H&E staining, immunohistochemistry (IHC) for CD45, and TUNEL assays. Results TRIM13 expression was rapidly upregulated in DCs following septic challenge. Deletion of TRIM13 in DCs disrupted the endoplasmic reticulum (ER)-associated degradation (ERAD) and ER-selective autophagy (ER-phagy)-mediated degradation of the stimulator of interferon genes (STING), leading to sustained STING activation and enhanced DC function. STING signaling promoted the p-IRF3 nuclear translocation, NLRP3 inflammasome priming, and transient DC pyroptosis, thereby exacerbating hyperinflammation in the acute phase of sepsis. Over the longer term, prolonged STING signaling inhibited DCs from adopting the immunosuppressive phenotype and promoting the DC-mediated immune response. Ultimately, TRIM13 deficiency in DCs ameliorated sepsis-induced immunosuppression, preserved organ function in the late phase of sepsis, and reduced overall mortality in septic mice. Conclusions TRIM13 acts as a key negative regulator of DC function during sepsis. Restricting TRIM13 sustains DC immunostimulatory property, counteracts sepsis-induced immunosuppression, and improves survival outcomes. These findings highlight TRIM13 as a potential therapeutic target for sepsis management.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704200","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 : 2025-11-24eCollection Date: 2026-01-01DOI: 10.1093/burnst/tkaf075
Feras Almujalli, Ali Asiri, Jon Hazeldine, Jon Bishop, Naiem S Moiemen, Paul Harrison
{"title":"Nucleated red blood cells as early indicators of sepsis in severe burns.","authors":"Feras Almujalli, Ali Asiri, Jon Hazeldine, Jon Bishop, Naiem S Moiemen, Paul Harrison","doi":"10.1093/burnst/tkaf075","DOIUrl":"10.1093/burnst/tkaf075","url":null,"abstract":"","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"14 ","pages":"tkaf075"},"PeriodicalIF":9.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12774814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932168","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 Diabetic wound healing is often impaired due to the high-glucose microenvironment in patients. Among the relevant factors, bacterial infection and overproduction of reactive oxygen species (ROS) have critical roles, and sustained oxidative stress further impairs angiogenesis and increases apoptosis, thereby hindering wound repair. To reduce these effects, we aimed to develop an injectable temperature-sensitive cellulose hydrogel exhibiting anti-apoptotic, oxidative stress-attenuating, antimicrobial, and multi-species enzymatic activities. Methods By simulating the dual active sites of natural copper–zinc superoxide dismutase (CuZn-SOD), a bimetallic mimetic nanoenzyme (Cu/Zn-metal–organic framework (MOF)) was synthesized. Subsequently, Cu/Zn-MOF was incorporated into a hydroxypropyl methylcellulose hydrogel, and the gelation temperature was adjusted to enable a sol-to-gel transition near physiological temperature. A rheometer was used to measure the gelation temperature, and scanning electron microscopy was performed to characterize the surface morphology. The hydrogels were evaluated for multiple enzyme-like activities, including those of SOD, glutathione peroxidase (GPx), thiol peroxidase (TPx), and ascorbate peroxidase (APx). Mouse fibroblasts (L929 cells) and human umbilical vein endothelial cells were used to assess antioxidant, pro-migratory, pro-angiogenic, and anti-apoptotic properties. Antimicrobial activity was assessed against Escherichia coli and Staphylococcus aureus. Western blotting was performed to verify potential anti-inflammatory mechanisms. Finally, wound and infected-wound models were established in diabetic mice to evaluate the hydrogel’s effects on wound repair. Results The hydrogel exhibited a sol-to-gel transition at 37°C and demonstrated favorable injectability and hydrophilicity, providing a moist healing environment. The Cu/Zn-MOF nanoenzymes demonstrated four enzyme-like activities (SOD, GPx, TPx, and APx), enabling cascade ROS scavenging, which was further confirmed in cellular experiments. The Cu/Zn-MOF nanoenzymes also modulated Sirt1/nuclear factor-κ beta expression to influence inflammatory factor release, thereby exhibiting strong anti-inflammatory activity. The hydrogel also exerted cell migration, angiogenesis, and anti-apoptotic effects. Antimicrobial assays showed kill rates of 99.39% and 99.67% against E. coli and S. aureus, respectively. In a diabetic mouse wound model, the hydrogel significantly enhanced pro-healing effects by promoting neovascularization and collagen deposition through ROS and bacterial clearance, thereby reducing the inflammatory response. Conclusions Biomimetic nanoenzymes were synthesized and incorporated into temperature-sensitive injectable hydrogels, which exhibited strong antioxidant and antimicrobial activities that have considerable potential for diabetic wound therapy.
{"title":"Multi-enzyme active temperature-sensitive hydrogel with reactive oxygen species scavenging and antimicrobial capacity for diabetic wound repair","authors":"Wenxuan Fan, Ji Cheng, Yonghai Wang, Hanjing Lu, Jiacheng Li, Hanbin Deng, Xingxin Guo, Huwen Wu, Peishen Zhang, Han Zhou, Ding Luo, Zuojia Guo, Jinghua Li, Shaowen Cheng","doi":"10.1093/burnst/tkaf076","DOIUrl":"https://doi.org/10.1093/burnst/tkaf076","url":null,"abstract":"Background Diabetic wound healing is often impaired due to the high-glucose microenvironment in patients. Among the relevant factors, bacterial infection and overproduction of reactive oxygen species (ROS) have critical roles, and sustained oxidative stress further impairs angiogenesis and increases apoptosis, thereby hindering wound repair. To reduce these effects, we aimed to develop an injectable temperature-sensitive cellulose hydrogel exhibiting anti-apoptotic, oxidative stress-attenuating, antimicrobial, and multi-species enzymatic activities. Methods By simulating the dual active sites of natural copper–zinc superoxide dismutase (CuZn-SOD), a bimetallic mimetic nanoenzyme (Cu/Zn-metal–organic framework (MOF)) was synthesized. Subsequently, Cu/Zn-MOF was incorporated into a hydroxypropyl methylcellulose hydrogel, and the gelation temperature was adjusted to enable a sol-to-gel transition near physiological temperature. A rheometer was used to measure the gelation temperature, and scanning electron microscopy was performed to characterize the surface morphology. The hydrogels were evaluated for multiple enzyme-like activities, including those of SOD, glutathione peroxidase (GPx), thiol peroxidase (TPx), and ascorbate peroxidase (APx). Mouse fibroblasts (L929 cells) and human umbilical vein endothelial cells were used to assess antioxidant, pro-migratory, pro-angiogenic, and anti-apoptotic properties. Antimicrobial activity was assessed against Escherichia coli and Staphylococcus aureus. Western blotting was performed to verify potential anti-inflammatory mechanisms. Finally, wound and infected-wound models were established in diabetic mice to evaluate the hydrogel’s effects on wound repair. Results The hydrogel exhibited a sol-to-gel transition at 37°C and demonstrated favorable injectability and hydrophilicity, providing a moist healing environment. The Cu/Zn-MOF nanoenzymes demonstrated four enzyme-like activities (SOD, GPx, TPx, and APx), enabling cascade ROS scavenging, which was further confirmed in cellular experiments. The Cu/Zn-MOF nanoenzymes also modulated Sirt1/nuclear factor-κ beta expression to influence inflammatory factor release, thereby exhibiting strong anti-inflammatory activity. The hydrogel also exerted cell migration, angiogenesis, and anti-apoptotic effects. Antimicrobial assays showed kill rates of 99.39% and 99.67% against E. coli and S. aureus, respectively. In a diabetic mouse wound model, the hydrogel significantly enhanced pro-healing effects by promoting neovascularization and collagen deposition through ROS and bacterial clearance, thereby reducing the inflammatory response. Conclusions Biomimetic nanoenzymes were synthesized and incorporated into temperature-sensitive injectable hydrogels, which exhibited strong antioxidant and antimicrobial activities that have considerable potential for diabetic wound therapy.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"44 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583119","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}
Trauma represents a significant global health issue, often resulting in devastating and long-lasting effects on the body throughout a patient’s life. Organ inflammation and dysfunction caused by trauma present additional challenges for clinicians. Therefore, understanding the cellular and molecular mechanisms of post-trauma systemic inflammation and organ dysfunction is essential for improving the management of trauma. This review aims to summarize current updates on the findings that explore different mechanisms of trauma-induced inflammation and organ dysfunction, highlighting the recent understanding of the vital roles of damage-associated molecular patterns (DAMPs), trauma-induced cell death, organ–organ cross-talk pathways, and the gut microbiota in the development and progression of post-traumatic systemic inflammation. We also discuss new approaches that can potentially guide further investigations of trauma diagnosis, treatment, and prognosis.
{"title":"Advances in Cellular and Molecular Mechanisms of Trauma-Induced Organ Inflammation and Dysfunction","authors":"Jieyan Wang, Hui Liang, Jie Fan","doi":"10.1093/burnst/tkaf074","DOIUrl":"https://doi.org/10.1093/burnst/tkaf074","url":null,"abstract":"Trauma represents a significant global health issue, often resulting in devastating and long-lasting effects on the body throughout a patient’s life. Organ inflammation and dysfunction caused by trauma present additional challenges for clinicians. Therefore, understanding the cellular and molecular mechanisms of post-trauma systemic inflammation and organ dysfunction is essential for improving the management of trauma. This review aims to summarize current updates on the findings that explore different mechanisms of trauma-induced inflammation and organ dysfunction, highlighting the recent understanding of the vital roles of damage-associated molecular patterns (DAMPs), trauma-induced cell death, organ–organ cross-talk pathways, and the gut microbiota in the development and progression of post-traumatic systemic inflammation. We also discuss new approaches that can potentially guide further investigations of trauma diagnosis, treatment, and prognosis.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553310","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}
Diabetic foot (DF) is a prevalent and significant complication of diabetes mellitus. The primary factors that contribute to amputation and mortality in DF patients are multifaceted and include foot deformities, ulcers, ischemia, and potential concurrent infections. To further standardize DF prevention and treatment in China, improve consistency in DF diagnosis and treatment, and promote the development of a specialized tiered care system, the Chinese Burn Association (CBA), the Yangtze River Delta Integrated Diabetic Foot Alliance (YRD-DFA), and the Editorial Committee of the Chinese Journal of Burns and Wound Repair (Chin J Burns) established a multidisciplinary expert team. The team identified clinical issues concerning the diagnosis, treatment, and prevention of DF via the PICO framework, assessed the quality of relevant evidence using the GRADE system, and ultimately formulated a consensus titled ‘Practical Guidelines for the Prevention and Management of Diabetic Foot Disease in China’. The guidelines include 37 recommendations that address comprehensive medical assessment; internal medical treatments, including treatments related to blood glucose, blood pressure, and blood lipid control; antithrombotic and anti-infection therapy; perioperative risk assessment and management; surgical interventions, such as debridement, vascular reconstruction, and tissue repair; foot disease prevention; multidisciplinary collaboration; and the establishment of a hierarchical diagnosis and treatment system, with the objective of guiding clinical practice for managing DF in China.
{"title":"Practical Guidelines for the Prevention and Management of Diabetic Foot Disease in China","authors":"Gaoxing Luo, Yan Liu, Aiping Wang","doi":"10.1093/burnst/tkaf064","DOIUrl":"https://doi.org/10.1093/burnst/tkaf064","url":null,"abstract":"Diabetic foot (DF) is a prevalent and significant complication of diabetes mellitus. The primary factors that contribute to amputation and mortality in DF patients are multifaceted and include foot deformities, ulcers, ischemia, and potential concurrent infections. To further standardize DF prevention and treatment in China, improve consistency in DF diagnosis and treatment, and promote the development of a specialized tiered care system, the Chinese Burn Association (CBA), the Yangtze River Delta Integrated Diabetic Foot Alliance (YRD-DFA), and the Editorial Committee of the Chinese Journal of Burns and Wound Repair (Chin J Burns) established a multidisciplinary expert team. The team identified clinical issues concerning the diagnosis, treatment, and prevention of DF via the PICO framework, assessed the quality of relevant evidence using the GRADE system, and ultimately formulated a consensus titled ‘Practical Guidelines for the Prevention and Management of Diabetic Foot Disease in China’. The guidelines include 37 recommendations that address comprehensive medical assessment; internal medical treatments, including treatments related to blood glucose, blood pressure, and blood lipid control; antithrombotic and anti-infection therapy; perioperative risk assessment and management; surgical interventions, such as debridement, vascular reconstruction, and tissue repair; foot disease prevention; multidisciplinary collaboration; and the establishment of a hierarchical diagnosis and treatment system, with the objective of guiding clinical practice for managing DF in China.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484863","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 accumulation of intracellular glycolytic lactate is a hallmark characteristic of chondrocytes. Histone lactylation, a post-translational modification mediated by lactate, plays a pivotal role in regulating the physiological functions of chondrocytes and contributes to the pathogenesis of posttraumatic osteoarthritis. This study was designed to investigate the role of glycolytic lactate-dependent histone H3 lysine 56 lactylation (H3K56la) in modulating the synthesis of type II collagen in chondrocytes. Furthermore, through a combination of laboratory-based and animal experimental approaches, the study sought to uncover new insights into potential therapeutic strategies for the management of posttraumatic osteoarthritis. Methods In in vitro experiments, the researchers first conducted assays to inhibit and induce histone lactylation in chondrocytes, subsequently measuring changes in the expression levels of hypoxia-inducible factor 1 alpha (HIF 1α) and the type II collagen alpha 1 chain gene (Col2a1). Next, we assessed alterations in intracellular lactylation levels and Col2a1 expression following either knockdown or overexpression of HIF 1α in chondrocytes. To further elucidate the regulatory relationship between HIF 1α and Col2a1, chromatin immunoprecipitation (ChIP) assays were performed to investigate the transcriptional control exerted by HIF 1α on the Col2a1 gene promoter. In addition, murine models of posttraumatic osteoarthritis were developed using anterior cruciate ligament transection (ACLT) surgery. Both in vivo and in vitro experiments were then carried out to explore the chondroprotective mechanisms and therapeutic potential associated with modulation of histone lactylation in chondrocytes. Results Induction of histone lactylation in chondrocytes led to a significant upregulation of HIF 1α expression. Conversely, knockdown of HIF 1α resulted in a marked reduction in both H3K56 lactylation and Col2a1 expression. It was found that H3K56la and HIF 1α functioned synergistically to positively regulate collagen synthesis, with HIF 1α directly binding to the promoter region of the Col2a1 gene to enhance its transcription. Treatment with α-ketoglutarate modified the cellular redox state and contributed to increased expression of both H3K56la and Col2a1. Conclusions The glycolytic lactate/H3K56la/HIF 1α regulatory axis plays a positive regulatory role in the synthesis of type II collagen in chondrocytes by facilitating the binding of HIF 1α to the Col2a1 gene promoter. Activation of this molecular pathway holds promise as a novel therapeutic strategy for the treatment of posttraumatic osteoarthritis.
{"title":"H3K56 lactylation promotes collagen II synthesis to modulate chondrocyte metabolism in posttraumatic osteoarthritis","authors":"Zicai Dong, Di Liu, Guangyun Hu, Zeyu Yang, Qin Shu, Qijie Dai, Hao Tang, Chuan Yang, Chunrong Zhao, Xiaoshan Gong, Rujie Wang, Weikai Kong, Shiwu Dong","doi":"10.1093/burnst/tkaf073","DOIUrl":"https://doi.org/10.1093/burnst/tkaf073","url":null,"abstract":"Background The accumulation of intracellular glycolytic lactate is a hallmark characteristic of chondrocytes. Histone lactylation, a post-translational modification mediated by lactate, plays a pivotal role in regulating the physiological functions of chondrocytes and contributes to the pathogenesis of posttraumatic osteoarthritis. This study was designed to investigate the role of glycolytic lactate-dependent histone H3 lysine 56 lactylation (H3K56la) in modulating the synthesis of type II collagen in chondrocytes. Furthermore, through a combination of laboratory-based and animal experimental approaches, the study sought to uncover new insights into potential therapeutic strategies for the management of posttraumatic osteoarthritis. Methods In in vitro experiments, the researchers first conducted assays to inhibit and induce histone lactylation in chondrocytes, subsequently measuring changes in the expression levels of hypoxia-inducible factor 1 alpha (HIF 1α) and the type II collagen alpha 1 chain gene (Col2a1). Next, we assessed alterations in intracellular lactylation levels and Col2a1 expression following either knockdown or overexpression of HIF 1α in chondrocytes. To further elucidate the regulatory relationship between HIF 1α and Col2a1, chromatin immunoprecipitation (ChIP) assays were performed to investigate the transcriptional control exerted by HIF 1α on the Col2a1 gene promoter. In addition, murine models of posttraumatic osteoarthritis were developed using anterior cruciate ligament transection (ACLT) surgery. Both in vivo and in vitro experiments were then carried out to explore the chondroprotective mechanisms and therapeutic potential associated with modulation of histone lactylation in chondrocytes. Results Induction of histone lactylation in chondrocytes led to a significant upregulation of HIF 1α expression. Conversely, knockdown of HIF 1α resulted in a marked reduction in both H3K56 lactylation and Col2a1 expression. It was found that H3K56la and HIF 1α functioned synergistically to positively regulate collagen synthesis, with HIF 1α directly binding to the promoter region of the Col2a1 gene to enhance its transcription. Treatment with α-ketoglutarate modified the cellular redox state and contributed to increased expression of both H3K56la and Col2a1. Conclusions The glycolytic lactate/H3K56la/HIF 1α regulatory axis plays a positive regulatory role in the synthesis of type II collagen in chondrocytes by facilitating the binding of HIF 1α to the Col2a1 gene promoter. Activation of this molecular pathway holds promise as a novel therapeutic strategy for the treatment of posttraumatic osteoarthritis.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"3 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472876","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 Infectious bone defects are characterized by persistent bacterial invasion and an immune microenvironment imbalance, which significantly hinders bone regeneration. Recently, numerous bone repair materials have been developed to address the complex pathological microenvironment associated with infectious bone defects. However, dynamic changes in the defect size after infectious debridement pose a significant challenge for achieving effective bone integration of artificial bone grafts. Methods Using low-temperature printing combined with the freeze-drying technology, a shape-memory scaffold with a biomimetic porous structure of cancellous bones was fabricated by compositing left-handed poly(L-lactic acid)-trimethylene carbonate (PLLA-TMC) with citric acid-modified hydroxyapatite (CHA). The scaffold (PT/CHA) was further coated with a metal-polyphenol network tannic acid-magnesium (TA-Mg) on its surface through the "mussel" effect, enabling the sequential treatment of infectious bone defects. Results The scaffold can adaptively integrate with defect interfaces at the physiological temperature (37°C), achieving superior bone integration performance. The incorporation of citric-acid-modified hydroxyapatite effectively optimizes the polymer-inorganic phase printing ink system, significantly enhancing the mechanical strength and mineralization capacity of the scaffold. Meanwhile, the external tannic-acid-magnesium metal-polyphenol coating (TA-Mg) demonstrates excellent pathogen clearance properties both in vitro and in vivo. It also influences macrophage polarization to regulate the immune microenvironment, ultimately promoting bone regeneration in infectious bone defects. Conclusions The PT/CHA@TA-Mg scaffold achieves bone integration through adaptive filling and enables the multi-stage treatment of infectious bone defects via antibacterial, immune-regulatory and osteogenic differentiation.
{"title":"Sequential treatment of infectious bone defects with 3D-printed body temperature-responsive shape memory scaffold coated with metal-polyphenol layers","authors":"Shuhao Yang, Qianshui Hu, Yingkun Hu, Zhengguang Pu, Yixuan Lan, Haoming Wu, Gaohui Zhu, Zhixiang Gao, Jianye Yang, Shuai Tan, Ning Hu, Xulin Hu, Leilei Qin","doi":"10.1093/burnst/tkaf072","DOIUrl":"https://doi.org/10.1093/burnst/tkaf072","url":null,"abstract":"Background Infectious bone defects are characterized by persistent bacterial invasion and an immune microenvironment imbalance, which significantly hinders bone regeneration. Recently, numerous bone repair materials have been developed to address the complex pathological microenvironment associated with infectious bone defects. However, dynamic changes in the defect size after infectious debridement pose a significant challenge for achieving effective bone integration of artificial bone grafts. Methods Using low-temperature printing combined with the freeze-drying technology, a shape-memory scaffold with a biomimetic porous structure of cancellous bones was fabricated by compositing left-handed poly(L-lactic acid)-trimethylene carbonate (PLLA-TMC) with citric acid-modified hydroxyapatite (CHA). The scaffold (PT/CHA) was further coated with a metal-polyphenol network tannic acid-magnesium (TA-Mg) on its surface through the \"mussel\" effect, enabling the sequential treatment of infectious bone defects. Results The scaffold can adaptively integrate with defect interfaces at the physiological temperature (37°C), achieving superior bone integration performance. The incorporation of citric-acid-modified hydroxyapatite effectively optimizes the polymer-inorganic phase printing ink system, significantly enhancing the mechanical strength and mineralization capacity of the scaffold. Meanwhile, the external tannic-acid-magnesium metal-polyphenol coating (TA-Mg) demonstrates excellent pathogen clearance properties both in vitro and in vivo. It also influences macrophage polarization to regulate the immune microenvironment, ultimately promoting bone regeneration in infectious bone defects. Conclusions The PT/CHA@TA-Mg scaffold achieves bone integration through adaptive filling and enables the multi-stage treatment of infectious bone defects via antibacterial, immune-regulatory and osteogenic differentiation.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"45 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145478324","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}
Punit Bhattachan, Zachary Ricciuti, Fadi Khalaf, Marc G Jeschke
Burn injury remains a major global health challenge, causing an estimated 180,000 deaths annually. The marked heterogeneity in burn severity, complications, and outcomes highlights the need for more objective and efficient evaluation strategies. Artificial intelligence (AI) has emerged as a promising approach to support clinical decision-making and improve patient care in this field. In this narrative review, we summarize the growing applications of AI in burn care, including the assessment of burn depth and total body surface area, monitoring of wound healing, prediction of post-burn complications, and estimation of clinical outcomes. AI-based models have demonstrated strong performance in automating wound assessment, optimizing fluid resuscitation, and predicting complications such as sepsis, inhalation injury, and acute kidney injury. Furthermore, AI-driven prediction of mortality risk and hospital length of stay has shown potential to inform early interventions and improve resource allocation. Despite encouraging progress, most studies to date rely on small, single-center datasets and limited model validation, underscoring the need for larger, multi-institutional efforts and standardized data sharing. Integrating AI into burn management holds great promise for enhancing diagnostic precision, forecasting outcomes, and personalizing treatment strategies. As these technologies advance, clinician familiarity and collaboration with AI tools will be critical to fully realize their potential in transforming burn care.
{"title":"The Role of Artificial Intelligence in Burn Assessment, Complication Diagnosis, and Outcome Prediction: A Narrative Review","authors":"Punit Bhattachan, Zachary Ricciuti, Fadi Khalaf, Marc G Jeschke","doi":"10.1093/burnst/tkaf071","DOIUrl":"https://doi.org/10.1093/burnst/tkaf071","url":null,"abstract":"Burn injury remains a major global health challenge, causing an estimated 180,000 deaths annually. The marked heterogeneity in burn severity, complications, and outcomes highlights the need for more objective and efficient evaluation strategies. Artificial intelligence (AI) has emerged as a promising approach to support clinical decision-making and improve patient care in this field. In this narrative review, we summarize the growing applications of AI in burn care, including the assessment of burn depth and total body surface area, monitoring of wound healing, prediction of post-burn complications, and estimation of clinical outcomes. AI-based models have demonstrated strong performance in automating wound assessment, optimizing fluid resuscitation, and predicting complications such as sepsis, inhalation injury, and acute kidney injury. Furthermore, AI-driven prediction of mortality risk and hospital length of stay has shown potential to inform early interventions and improve resource allocation. Despite encouraging progress, most studies to date rely on small, single-center datasets and limited model validation, underscoring the need for larger, multi-institutional efforts and standardized data sharing. Integrating AI into burn management holds great promise for enhancing diagnostic precision, forecasting outcomes, and personalizing treatment strategies. As these technologies advance, clinician familiarity and collaboration with AI tools will be critical to fully realize their potential in transforming burn care.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"84 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145404677","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}
Mengqi Zhang, Dan Xiao, Ting He, Lifei Guo, Xuekang Yang
Sepsis-associated encephalopathy (SAE) is a secondary cerebral dysfunction of in the central nervous system (CNS) caused by sepsis and is associated with high mortality rate and poor prognosis. It significantly affects the quality of life of survivors. The pathological mechanisms associated with SAE include dysfunction of the blood–brain barrier (BBB), activation of glial cells, ischaemic injury, leukocyte transmigration, and disturbances in neurotransmitters. The mechanisms of SAE interact with and contribute to its development. Numerous studies have demonstrated that the intestinal microbiota affects not only the health of the gut but also that of other organs. Throughout the progression of SAE, alterations in the gut microbiome composition lead to the production of toxic substances that damage the intestinal barrier and enter the bloodstream. This damage negatively affects BBB permeability and initiates a cascade of neuroinflammatory responses that result in neuronal injury. Conversely, specific microbiome-derived derivatives play exhibit a neuroprotective role in regulating brain function. Therefore, gut–brain crosstalk may be a crucial factor in brain dysfunction. This paper reviews the relationship between the intestinal microbiota and SAE, aiming to explore the role of the intestinal microbiota in SAE and potential therapeutic targets.
{"title":"Role of the Intestinal Microbiota in Sepsis-associated Encephalopathy","authors":"Mengqi Zhang, Dan Xiao, Ting He, Lifei Guo, Xuekang Yang","doi":"10.1093/burnst/tkaf070","DOIUrl":"https://doi.org/10.1093/burnst/tkaf070","url":null,"abstract":"Sepsis-associated encephalopathy (SAE) is a secondary cerebral dysfunction of in the central nervous system (CNS) caused by sepsis and is associated with high mortality rate and poor prognosis. It significantly affects the quality of life of survivors. The pathological mechanisms associated with SAE include dysfunction of the blood–brain barrier (BBB), activation of glial cells, ischaemic injury, leukocyte transmigration, and disturbances in neurotransmitters. The mechanisms of SAE interact with and contribute to its development. Numerous studies have demonstrated that the intestinal microbiota affects not only the health of the gut but also that of other organs. Throughout the progression of SAE, alterations in the gut microbiome composition lead to the production of toxic substances that damage the intestinal barrier and enter the bloodstream. This damage negatively affects BBB permeability and initiates a cascade of neuroinflammatory responses that result in neuronal injury. Conversely, specific microbiome-derived derivatives play exhibit a neuroprotective role in regulating brain function. Therefore, gut–brain crosstalk may be a crucial factor in brain dysfunction. This paper reviews the relationship between the intestinal microbiota and SAE, aiming to explore the role of the intestinal microbiota in SAE and potential therapeutic targets.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"21 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145382343","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 expression of CX3CR1 is regulated by the gut microbiota and is correlated with the prognosis of sepsis in patients. However, the underlying mechanism has remained uncertain. Methods Mice were fed a mixture of antibiotics to establish a pseudogerm-free mouse model and then infected with Klebsiella pneumoniae. Fecal microbiota transplantation (FMT) was performed on microbiota-depleted mice, and 16S rRNA gene sequencing and targeted metabolomics were used to identify the key metabolites. Flow cytometry was employed to analyze the phenotypes of natural killer (NK) cells. Butyric acid was added as a supplement for rescue. Next, NK92 cells were pretreated with butyric acid to explore the potential signaling pathways involved. Results In the animal study, we revealed that the expression of CX3CR1 on NK cells depended on the intestinal microbiota and its metabolites, which were related to the survival rates of gut microbiota-depleted mice after K. pneumoniae infection. FMT increased the percentage of CX3CR1+ NK cells in the lungs of these mice, restored the disordered microbiota and metabolites, and alleviated the lung injury induced by infection. Among the metabolites, butyric acid was identified as the key metabolite and was shown to increase the proportion of CX3CR1+ NK cells, reduce bacterial loads, increase lung tissue damage, and increase survival rates. In vitro, butyric acid activated the PI3K/AKT pathway in NK92 cells, promoted CX3CR1 expression, and enhanced NK cell activity and migration ability. Conclusions We concluded that butyric acid alleviated K. pneumoniae-induced lung injury by regulating CX3CR1+ NK cells via the PI3K/AKT pathway.
{"title":"Gut microbiota Metabolite Butyric Acid Alleviated Klebsiella Pneumoniae induced lung injury by Regulating CX3CR1 +NK via PI3K/AKT Pathway","authors":"Sucheng Mu, Meijia Chang, Yongqi Shen, Xingyue Wu, Yi Han, Hao Xiang, Yue Luo, Yao Chen, Huajun Zheng, Zhenju Song, Chaoyang Tong","doi":"10.1093/burnst/tkaf069","DOIUrl":"https://doi.org/10.1093/burnst/tkaf069","url":null,"abstract":"Background The expression of CX3CR1 is regulated by the gut microbiota and is correlated with the prognosis of sepsis in patients. However, the underlying mechanism has remained uncertain. Methods Mice were fed a mixture of antibiotics to establish a pseudogerm-free mouse model and then infected with Klebsiella pneumoniae. Fecal microbiota transplantation (FMT) was performed on microbiota-depleted mice, and 16S rRNA gene sequencing and targeted metabolomics were used to identify the key metabolites. Flow cytometry was employed to analyze the phenotypes of natural killer (NK) cells. Butyric acid was added as a supplement for rescue. Next, NK92 cells were pretreated with butyric acid to explore the potential signaling pathways involved. Results In the animal study, we revealed that the expression of CX3CR1 on NK cells depended on the intestinal microbiota and its metabolites, which were related to the survival rates of gut microbiota-depleted mice after K. pneumoniae infection. FMT increased the percentage of CX3CR1+ NK cells in the lungs of these mice, restored the disordered microbiota and metabolites, and alleviated the lung injury induced by infection. Among the metabolites, butyric acid was identified as the key metabolite and was shown to increase the proportion of CX3CR1+ NK cells, reduce bacterial loads, increase lung tissue damage, and increase survival rates. In vitro, butyric acid activated the PI3K/AKT pathway in NK92 cells, promoted CX3CR1 expression, and enhanced NK cell activity and migration ability. Conclusions We concluded that butyric acid alleviated K. pneumoniae-induced lung injury by regulating CX3CR1+ NK cells via the PI3K/AKT pathway.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"127 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145382345","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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