Pub Date : 2025-02-17eCollection Date: 2025-01-01DOI: 10.1093/burnst/tkae086
Ugo Lancien, Maria Sbeih, Alexandra Poinas, Pierre Perrot, Selim Aractingi, Amir Khammari, Brigitte Dréno
{"title":"An easy and reproducible method for a large-zone deep partial-thickness burn model in the mini-pig.","authors":"Ugo Lancien, Maria Sbeih, Alexandra Poinas, Pierre Perrot, Selim Aractingi, Amir Khammari, Brigitte Dréno","doi":"10.1093/burnst/tkae086","DOIUrl":"10.1093/burnst/tkae086","url":null,"abstract":"","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"13 ","pages":"tkae086"},"PeriodicalIF":6.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440298","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 Ischemic injury is a primary cause of distal flap necrosis. Previous studies have shown that Flufenamic acid (FFA) can reduce inflammation, decrease oxidative stress (OS), and promote angiogenesis, suggesting its potential role in protecting flaps from ischemic damage. This study investigated the effects and mechanisms of FFA in enhancing the survival of ischemic flaps. Methods The viability of ischemic flaps was evaluated using laser doppler blood flow (LDBF) and survival rates. We examined levels of pyroptosis, OS, transcription factor E3 (TFE3)-induced autophagy, and elements of the AMPK-TRPML1-Calcineurin pathway through western blotting (WB), immunofluorescence (IF), molecular docking (MD), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR). Results The findings suggest that FFA significantly enhances the viability of ischemic flaps. The improvement in flap survival associated with FFA can be attributed to increased autophagy, diminished OS, and the suppression of pyroptosis. Notably, the promotion of autophagy flux and an augmented resistance to OS are instrumental in curbing pyroptosis in these flaps. Activation of TFE3 by FFA promoted autophagy and diminished oxidative damage. The therapeutic effects of FFA were negated when TFE3 levels were decreased using adeno-associated virus (AAV)-TFE3shRNA. Additionally, FFA modified TFE3 activity through the AMPK-TRPML1-Calcineurin pathway. Conclusions FFA promotes ischemic flap survival via induction of autophagy and suppression of oxidative stress by activation of the AMPK-TRPML1-Calcineurin-TFE3 signaling pathway. These findings could have therapeutic implications.
{"title":"Flufenamic acid inhibits pyroptosis in ischemic flaps via the AMPK-TRPML1-Calcineurin signaling pathway","authors":"Liang Chen, Ningning Yang, Kongbin Chen, Yingying Huang, Xian Liu, Gaoxiang Yu, Fulin Wang, Yong Gou, Yi Wang, Xiaolang Lu, Yuqi Wang, Lipeng Zhu, Weiyang Gao, Jian Ding","doi":"10.1093/burnst/tkaf007","DOIUrl":"https://doi.org/10.1093/burnst/tkaf007","url":null,"abstract":"Background Ischemic injury is a primary cause of distal flap necrosis. Previous studies have shown that Flufenamic acid (FFA) can reduce inflammation, decrease oxidative stress (OS), and promote angiogenesis, suggesting its potential role in protecting flaps from ischemic damage. This study investigated the effects and mechanisms of FFA in enhancing the survival of ischemic flaps. Methods The viability of ischemic flaps was evaluated using laser doppler blood flow (LDBF) and survival rates. We examined levels of pyroptosis, OS, transcription factor E3 (TFE3)-induced autophagy, and elements of the AMPK-TRPML1-Calcineurin pathway through western blotting (WB), immunofluorescence (IF), molecular docking (MD), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR). Results The findings suggest that FFA significantly enhances the viability of ischemic flaps. The improvement in flap survival associated with FFA can be attributed to increased autophagy, diminished OS, and the suppression of pyroptosis. Notably, the promotion of autophagy flux and an augmented resistance to OS are instrumental in curbing pyroptosis in these flaps. Activation of TFE3 by FFA promoted autophagy and diminished oxidative damage. The therapeutic effects of FFA were negated when TFE3 levels were decreased using adeno-associated virus (AAV)-TFE3shRNA. Additionally, FFA modified TFE3 activity through the AMPK-TRPML1-Calcineurin pathway. Conclusions FFA promotes ischemic flap survival via induction of autophagy and suppression of oxidative stress by activation of the AMPK-TRPML1-Calcineurin-TFE3 signaling pathway. These findings could have therapeutic implications.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434938","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}
Haisheng Li, Ni Zhen, Shixu Lin, Ning Li, Yumei Zhang, Wei Luo, Zhenzhen Zhang, Xingang Wang, Chunmao Han, Zhiqiang Yuan, Gaoxing Luo
Background Airway obstruction is a common emergency in acute burns with high mortality. Tracheostomy is the most effective method to keep patency of airway and start mechanical ventilation. However, the indication of tracheostomy is challenging and controversial. We aimed to develop and validate a deployable machine learning (ML)-based decision support system to predict the necessity of tracheostomy for acute burn patients. Methods We enrolled 1011 burn patients from Southwest Hospital (2018–2020) for model development and feature selection. The final model was validated on an independent internal cross-temporal cohort (2021, n = 274) and an external cross-institutional cohort (Second Affiliated Hospital of Zhejiang University School of Medicine 2020–2021, n = 376). To improve the model’s deployment and interpretability, an ML-based nomogram, an online calculator, and an abbreviated scale were constructed and validated. Results The optimal model was the eXtreme Gradient Boosting classifier (XGB), which achieved an AUROC of 0.973 and AUPRC of 0.879 in training dataset, and AUROCs of greater than 0.95 in both cross-temporal and cross-institutional validation. Moreover, it kept stable discriminatory ability in validation subgroups stratified by sex, age, burn area, and inhalation injury (AUROC ranging 0.903–0.990). The analysis of calibration curve, decision curve, and score distribution proved the feasibility and reliability of the ML-based nomogram, abbreviated scale, and online calculator. Conclusions The developed system has strong predictive ability and generalizability in cross-temporal and cross-institutional evaluations. The nomogram, online calculator, and abbreviated scale based on machine learning show comparable prediction performance and can be deployed in broader application scenarios, especially in resource-limited clinical environments.
{"title":"Deployable machine learning-based decision support system for tracheostomy in acute burn patients","authors":"Haisheng Li, Ni Zhen, Shixu Lin, Ning Li, Yumei Zhang, Wei Luo, Zhenzhen Zhang, Xingang Wang, Chunmao Han, Zhiqiang Yuan, Gaoxing Luo","doi":"10.1093/burnst/tkaf010","DOIUrl":"https://doi.org/10.1093/burnst/tkaf010","url":null,"abstract":"Background Airway obstruction is a common emergency in acute burns with high mortality. Tracheostomy is the most effective method to keep patency of airway and start mechanical ventilation. However, the indication of tracheostomy is challenging and controversial. We aimed to develop and validate a deployable machine learning (ML)-based decision support system to predict the necessity of tracheostomy for acute burn patients. Methods We enrolled 1011 burn patients from Southwest Hospital (2018–2020) for model development and feature selection. The final model was validated on an independent internal cross-temporal cohort (2021, n = 274) and an external cross-institutional cohort (Second Affiliated Hospital of Zhejiang University School of Medicine 2020–2021, n = 376). To improve the model’s deployment and interpretability, an ML-based nomogram, an online calculator, and an abbreviated scale were constructed and validated. Results The optimal model was the eXtreme Gradient Boosting classifier (XGB), which achieved an AUROC of 0.973 and AUPRC of 0.879 in training dataset, and AUROCs of greater than 0.95 in both cross-temporal and cross-institutional validation. Moreover, it kept stable discriminatory ability in validation subgroups stratified by sex, age, burn area, and inhalation injury (AUROC ranging 0.903–0.990). The analysis of calibration curve, decision curve, and score distribution proved the feasibility and reliability of the ML-based nomogram, abbreviated scale, and online calculator. Conclusions The developed system has strong predictive ability and generalizability in cross-temporal and cross-institutional evaluations. The nomogram, online calculator, and abbreviated scale based on machine learning show comparable prediction performance and can be deployed in broader application scenarios, especially in resource-limited clinical environments.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"80 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434939","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}
Wound healing is a complex biological process involving multiple steps, including hemostasis, inflammation, proliferation, and remodeling. A novel form of regulated cell death, ferroptosis, has garnered attention because of its involvement in these processes. Ferroptosis is characterized by the accumulation of lipid peroxides and is tightly regulated by lipid metabolism, iron metabolism, and the lipid-peroxide repair network, all of which exert a significant influence on wound healing. This review highlights the current findings and emerging concepts regarding the multifaceted roles of ferroptosis throughout the stages of normal and chronic wound healing. Additionally, the potential of targeted interventions aimed at modulating ferroptosis to improve wound-healing outcomes is discussed.
{"title":"The emerging role and therapeutical implications of ferroptosis in wound healing","authors":"Yanan Zhao, Zhiyang Chen, Shenghao Xie, Feng Xiao, Qian Hu, Zhenyu Ju","doi":"10.1093/burnst/tkae082","DOIUrl":"https://doi.org/10.1093/burnst/tkae082","url":null,"abstract":"Wound healing is a complex biological process involving multiple steps, including hemostasis, inflammation, proliferation, and remodeling. A novel form of regulated cell death, ferroptosis, has garnered attention because of its involvement in these processes. Ferroptosis is characterized by the accumulation of lipid peroxides and is tightly regulated by lipid metabolism, iron metabolism, and the lipid-peroxide repair network, all of which exert a significant influence on wound healing. This review highlights the current findings and emerging concepts regarding the multifaceted roles of ferroptosis throughout the stages of normal and chronic wound healing. Additionally, the potential of targeted interventions aimed at modulating ferroptosis to improve wound-healing outcomes is discussed.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"66 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417388","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}
Xichao Jian, Yaping Deng, Shune Xiao, Fang Qi, Chengliang Deng
Diabetic wounds present a significant challenge in clinical treatment and are characterized by chronic inflammation, oxidative stress, impaired angiogenesis, peripheral neuropathy, and a heightened risk of infection during the healing process. By creating small channels in the surface of the skin, microneedle technology offers a minimally invasive and efficient approach for drug delivery and treatment. This article begins by outlining the biological foundation of normal skin wound healing and the unique pathophysiological mechanisms of diabetic wounds. It then delves into the various types, materials, and preparation processes of microneedles. The focus is on the application of multifunctional microneedles in diabetic wound treatment, highlighting their antibacterial, anti-inflammatory, immunomodulatory, antioxidant, angiogenic and neural repair properties. These multifunctional microneedles demonstrate synergistic therapeutic effects by directly influencing the wound microenvironment, ultimately accelerating the healing of diabetic wounds. The advancement of microneedle technology not only holds promise for enhancing the treatment outcomes of diabetic wounds but also offers new strategies for addressing other chronic wounds.
{"title":"Microneedles in diabetic wound care: multifunctional solutions for enhanced healing","authors":"Xichao Jian, Yaping Deng, Shune Xiao, Fang Qi, Chengliang Deng","doi":"10.1093/burnst/tkae076","DOIUrl":"https://doi.org/10.1093/burnst/tkae076","url":null,"abstract":"Diabetic wounds present a significant challenge in clinical treatment and are characterized by chronic inflammation, oxidative stress, impaired angiogenesis, peripheral neuropathy, and a heightened risk of infection during the healing process. By creating small channels in the surface of the skin, microneedle technology offers a minimally invasive and efficient approach for drug delivery and treatment. This article begins by outlining the biological foundation of normal skin wound healing and the unique pathophysiological mechanisms of diabetic wounds. It then delves into the various types, materials, and preparation processes of microneedles. The focus is on the application of multifunctional microneedles in diabetic wound treatment, highlighting their antibacterial, anti-inflammatory, immunomodulatory, antioxidant, angiogenic and neural repair properties. These multifunctional microneedles demonstrate synergistic therapeutic effects by directly influencing the wound microenvironment, ultimately accelerating the healing of diabetic wounds. The advancement of microneedle technology not only holds promise for enhancing the treatment outcomes of diabetic wounds but also offers new strategies for addressing other chronic wounds.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"79 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417387","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}
The epidermis is the outermost layer of the skin and acts as the primary barrier to protect the body. Dendritic epidermal T cells (DETCs), which are specifically distributed in epidermal tissues, play a crucial role in skin immune surveillance and wound healing. DETCs are one of the most important components of the epidermis and exert a steady-state monitoring function, facilitating wound healing and tissue regeneration after skin injury. Skin wounds are often linked to other pathological conditions such as ageing, ultraviolet radiation, and metabolic diseases such as diabetes mellitus and obesity. Therefore, it is crucial to investigate how DETCs regulate themselves and the external environment during these pathological states. DETCs interact closely with keratinocytes in the epidermis, and this intercellular interaction may be essential for maintaining health and integrity. In this review, we focus on the characteristics and underlying mechanisms of DETCs in maintaining epidermal homeostasis and re-epithelialization in different pathological states.
表皮是皮肤的最外层，是保护身体的主要屏障。树突状表皮T细胞（Dendritic epidermal T cells, DETCs）特异分布于表皮组织，在皮肤免疫监测和创面愈合中起着至关重要的作用。detc是表皮最重要的成分之一，发挥稳态监测功能，促进皮肤损伤后伤口愈合和组织再生。皮肤伤口通常与其他病理状况有关，如衰老、紫外线辐射和代谢疾病，如糖尿病和肥胖。因此，研究detc在这些病理状态下如何调节自身和外部环境是至关重要的。detc与表皮中的角质形成细胞密切相互作用，这种细胞间相互作用可能对维持健康和完整性至关重要。本文就detc在不同病理状态下维持表皮稳态和再上皮化的作用特点及机制进行综述。
{"title":"Roles of dendritic epidermal T cells in steady and different pathological states","authors":"Jiaqi Hao, Jie Zhang, Yan Liu","doi":"10.1093/burnst/tkae056","DOIUrl":"https://doi.org/10.1093/burnst/tkae056","url":null,"abstract":"The epidermis is the outermost layer of the skin and acts as the primary barrier to protect the body. Dendritic epidermal T cells (DETCs), which are specifically distributed in epidermal tissues, play a crucial role in skin immune surveillance and wound healing. DETCs are one of the most important components of the epidermis and exert a steady-state monitoring function, facilitating wound healing and tissue regeneration after skin injury. Skin wounds are often linked to other pathological conditions such as ageing, ultraviolet radiation, and metabolic diseases such as diabetes mellitus and obesity. Therefore, it is crucial to investigate how DETCs regulate themselves and the external environment during these pathological states. DETCs interact closely with keratinocytes in the epidermis, and this intercellular interaction may be essential for maintaining health and integrity. In this review, we focus on the characteristics and underlying mechanisms of DETCs in maintaining epidermal homeostasis and re-epithelialization in different pathological states.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"86 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393620","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}
Aline Yen Ling Wang, Huang-Kai Kao, Yen-Yu Liu, Charles Yuen Yung Loh
The engineered extracellular vesicles (EVs) derived from pluripotent stem cells are a new concept in regenerative medicine. These vesicles are secreted from the embryonic stem cells as well as the induced pluripotent stem cells (iPSCs) and are involved in the transfer of bioactive molecules required for cell signaling. This review describes the possibilities for their use in the modification of therapeutic approaches in regenerative medicine and targeted therapies. Pluripotent stem cells can differentiate into various cell types which can be useful for tissue engineering or to generate models of diseases in a dish. Compared to cell therapies, engineered EVs are characterized by lower immunogenicity, higher targetability, and improved stability. Some of the applications are angiogenic, tissue restorative, immunomodulatory, and gene therapies for the treatment of certain diseases. iPSC-derived engineered EVs find application in regenerative medicine, drug delivery systems, diagnostics of diseases, and hydrogel systems. In regenerative medicine, they can promote the restoration of cardiac, bone, cartilage, and corneal tissues. Engineered EVs are also employed in drug targeting to particular sites as well as in the diagnosis of diseases based on biomarkers and improving image contrast. Hydrogels that contain EVs provide a depot-based delivery system to slowly release drugs in a controlled manner which enhances tissue repair. Thus, the results described above demonstrate the potential of engineered PSC-EVs for various biomedical applications. Future work will be directed toward expanding the knowledge of engineered PSC-EVs and their possibilities to create new therapeutic approaches based on the functions of these vesicles.
{"title":"Engineered Extracellular Vesicles Derived from Pluripotent Stem Cells: A Cell-Free Approach to Regenerative Medicine","authors":"Aline Yen Ling Wang, Huang-Kai Kao, Yen-Yu Liu, Charles Yuen Yung Loh","doi":"10.1093/burnst/tkaf013","DOIUrl":"https://doi.org/10.1093/burnst/tkaf013","url":null,"abstract":"The engineered extracellular vesicles (EVs) derived from pluripotent stem cells are a new concept in regenerative medicine. These vesicles are secreted from the embryonic stem cells as well as the induced pluripotent stem cells (iPSCs) and are involved in the transfer of bioactive molecules required for cell signaling. This review describes the possibilities for their use in the modification of therapeutic approaches in regenerative medicine and targeted therapies. Pluripotent stem cells can differentiate into various cell types which can be useful for tissue engineering or to generate models of diseases in a dish. Compared to cell therapies, engineered EVs are characterized by lower immunogenicity, higher targetability, and improved stability. Some of the applications are angiogenic, tissue restorative, immunomodulatory, and gene therapies for the treatment of certain diseases. iPSC-derived engineered EVs find application in regenerative medicine, drug delivery systems, diagnostics of diseases, and hydrogel systems. In regenerative medicine, they can promote the restoration of cardiac, bone, cartilage, and corneal tissues. Engineered EVs are also employed in drug targeting to particular sites as well as in the diagnosis of diseases based on biomarkers and improving image contrast. Hydrogels that contain EVs provide a depot-based delivery system to slowly release drugs in a controlled manner which enhances tissue repair. Thus, the results described above demonstrate the potential of engineered PSC-EVs for various biomedical applications. Future work will be directed toward expanding the knowledge of engineered PSC-EVs and their possibilities to create new therapeutic approaches based on the functions of these vesicles.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"15 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393622","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 Peripheral nerves are easily damaged in accidental trauma due to their shallow location. Compared to the limited regeneration of the central nerve, the peripheral nerve has a certain regenerative ability after injury. However, this ability is not sufficient to achieve functional recovery. To increase the rate of regeneration after nerve injury, increasing regeneration-associated genes (RAGs) expression by transcription factors in neurons is necessary. Methods Sciatic nerve crush (SNC) animal models were generated in Sprague–Dawley (SD) rats. Bioinformatics analysis and real-time polymerase chain reaction (qPCR) were applied to detect genes expression; immunofluorescence staining and western blotting were applied to detect protein expression. The neurites outgrowth of cultured DRG neurons was performed to evaluate axon regeneration in vitro. Intrathecal injection of adeno-associated virus (AAV) was applied to suppress or overexpress the target in vivo. Following transfection, immunofluorescence staining of newborn axons’ marker (SCG10) in sciatic nerve after crush was used to evaluate the function of AT-rich interaction domain 5A (Arid5a) or docking protein 6 (Dok6) on axon regeneration. The binding between TF and the promoter of target genes was verified by chromatin immunoprecipitation (ChIP). Result has high activity in specific regenerating clusters and it accumulates specifically in the nucleus of DRG neurons after sciatic nerve injury. Upon Arid5a inhibition by siRNA, the outgrowth of neurites in vitro and the regeneration of axons in vivo were inhibited. In contrast, after Arid5a overexpression in rats, axon regeneration was significantly accelerated. In addition, Arid5a promotes the expression of Dok6 by binding to its promoter in DRG neurons. Suppression of Dok6 represses the neurites outgrowth of cultured DRG neurons, while its overexpression enhances axon regeneration in vivo. Furthermore, overexpression of Dok6 restored the impaired effect of Arid5a suppression on axon regeneration. Conclusions These findings indicate that axonal injury induced nucleus accumulation of Arid5a in neurons. Through Dok6, Arid5a accelerates axon regeneration of DRG neurons both in vitro and in vivo. This study enriched our understanding the function of Arid5a in the peripheral nervous system and the transcriptional regulatory network involved in neural regeneration.
{"title":"AT-rich interaction domain 5A facilitates axon regeneration through docking protein 6 in the peripheral nervous system","authors":"Zhixian Ren, Weixiao Huang, Xiaosong Gu, Lili Zhao","doi":"10.1093/burnst/tkaf012","DOIUrl":"https://doi.org/10.1093/burnst/tkaf012","url":null,"abstract":"Background Peripheral nerves are easily damaged in accidental trauma due to their shallow location. Compared to the limited regeneration of the central nerve, the peripheral nerve has a certain regenerative ability after injury. However, this ability is not sufficient to achieve functional recovery. To increase the rate of regeneration after nerve injury, increasing regeneration-associated genes (RAGs) expression by transcription factors in neurons is necessary. Methods Sciatic nerve crush (SNC) animal models were generated in Sprague–Dawley (SD) rats. Bioinformatics analysis and real-time polymerase chain reaction (qPCR) were applied to detect genes expression; immunofluorescence staining and western blotting were applied to detect protein expression. The neurites outgrowth of cultured DRG neurons was performed to evaluate axon regeneration in vitro. Intrathecal injection of adeno-associated virus (AAV) was applied to suppress or overexpress the target in vivo. Following transfection, immunofluorescence staining of newborn axons’ marker (SCG10) in sciatic nerve after crush was used to evaluate the function of AT-rich interaction domain 5A (Arid5a) or docking protein 6 (Dok6) on axon regeneration. The binding between TF and the promoter of target genes was verified by chromatin immunoprecipitation (ChIP). Result has high activity in specific regenerating clusters and it accumulates specifically in the nucleus of DRG neurons after sciatic nerve injury. Upon Arid5a inhibition by siRNA, the outgrowth of neurites in vitro and the regeneration of axons in vivo were inhibited. In contrast, after Arid5a overexpression in rats, axon regeneration was significantly accelerated. In addition, Arid5a promotes the expression of Dok6 by binding to its promoter in DRG neurons. Suppression of Dok6 represses the neurites outgrowth of cultured DRG neurons, while its overexpression enhances axon regeneration in vivo. Furthermore, overexpression of Dok6 restored the impaired effect of Arid5a suppression on axon regeneration. Conclusions These findings indicate that axonal injury induced nucleus accumulation of Arid5a in neurons. Through Dok6, Arid5a accelerates axon regeneration of DRG neurons both in vitro and in vivo. This study enriched our understanding the function of Arid5a in the peripheral nervous system and the transcriptional regulatory network involved in neural regeneration.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"21 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385514","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 : 2025-02-10eCollection Date: 2025-01-01DOI: 10.1093/burnst/tkae085
Folke Sjoberg, David Greenhalgh, Moustafa Elmasry, Islam Abdelrahman, Ahmed T El-Serafi, Ingrid Steinvall
{"title":"High early incidence of sepsis and its impact on organ dysfunction in burn trauma patients: a detailed and hypothesis generating study.","authors":"Folke Sjoberg, David Greenhalgh, Moustafa Elmasry, Islam Abdelrahman, Ahmed T El-Serafi, Ingrid Steinvall","doi":"10.1093/burnst/tkae085","DOIUrl":"10.1093/burnst/tkae085","url":null,"abstract":"","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"13 ","pages":"tkae085"},"PeriodicalIF":6.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390192","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}
Tissue regeneration is essential for repairing and restoring damaged tissues, which has significant implications for clinical outcomes. Understanding the cellular mechanisms and the role of the immune system in this process provides a basis for improved regenerative techniques. The emergence of nanomedicine has advanced this field by introducing nanoscale technology that offer precise control over therapeutic delivery and cellular interactions. By modulating immune responses, various immunotherapeutic approaches, including cytokine therapy and immune checkpoint inhibitors, can establish an optimal environment for tissue repair. This review summarizes recent findings and applications of nanomedicine-based immunotherapy in tissue regeneration. It highlights the properties and advantages of nanomedicine in immunotherapy, discusses recent progress in using nanocomposite biomaterials for tissue engineering, and addresses the challenges and future directions in this evolving field. This review aims to emphasize the promising potential of nanomedicine-based immunotherapy in tissue engineering, thereby contributing to the functional design and strategic development of next-generation nanomedicine for regenerative medicine.
{"title":"Nanomedicine-based immunotherapy for tissue regeneration","authors":"Song Li, Li Lu, Yuan Xiong, Jun Xiao","doi":"10.1093/burnst/tkaf015","DOIUrl":"https://doi.org/10.1093/burnst/tkaf015","url":null,"abstract":"Tissue regeneration is essential for repairing and restoring damaged tissues, which has significant implications for clinical outcomes. Understanding the cellular mechanisms and the role of the immune system in this process provides a basis for improved regenerative techniques. The emergence of nanomedicine has advanced this field by introducing nanoscale technology that offer precise control over therapeutic delivery and cellular interactions. By modulating immune responses, various immunotherapeutic approaches, including cytokine therapy and immune checkpoint inhibitors, can establish an optimal environment for tissue repair. This review summarizes recent findings and applications of nanomedicine-based immunotherapy in tissue regeneration. It highlights the properties and advantages of nanomedicine in immunotherapy, discusses recent progress in using nanocomposite biomaterials for tissue engineering, and addresses the challenges and future directions in this evolving field. This review aims to emphasize the promising potential of nanomedicine-based immunotherapy in tissue engineering, thereby contributing to the functional design and strategic development of next-generation nanomedicine for regenerative medicine.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"63 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385474","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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