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}
Li Pan, Lizheng Xie, Wenpei Yang, Shi Feng, Wenbao Mao, Lei Ye, Hongwei Cheng, Xiao Wu, Xiang Mao
In recent years, with the increasing volume of related research, it has become apparent that the liver and gut play important roles in the pathogenesis of neurological disorders. Considering the interactions among the brain, liver, and gut, the brain–liver–gut axis has been proposed and gradually recognized. In this article, we summarized the complex network of interactions within the brain–liver–gut axis, encompassing the vagus nerve, barrier permeability, immunity and inflammation, the blood–brain barrier, gut microbial metabolites, the gut barrier, neurotoxic metabolites, and beta-amyloid (Aβ) metabolism. We also elaborated on the impact of the brain–liver–gut axis on various neurological disorders. Furthermore, we outline several therapies aimed at modulating the brain–liver–gut axis, including antibiotics, probiotics and prebiotics, fecal microbiota transplantation (FMT), vagus nerve stimulation (VNS), and dietary interventions. The focus is on elucidating possible mechanisms underlying neurological disorders pathogenesis and identifying effective treatments that are based on our understanding of the brain–liver–gut axis.
{"title":"The role of the gut microbiome and brain-liver-gut Axis in neurological disorders","authors":"Li Pan, Lizheng Xie, Wenpei Yang, Shi Feng, Wenbao Mao, Lei Ye, Hongwei Cheng, Xiao Wu, Xiang Mao","doi":"10.1093/burnst/tkaf011","DOIUrl":"https://doi.org/10.1093/burnst/tkaf011","url":null,"abstract":"In recent years, with the increasing volume of related research, it has become apparent that the liver and gut play important roles in the pathogenesis of neurological disorders. Considering the interactions among the brain, liver, and gut, the brain–liver–gut axis has been proposed and gradually recognized. In this article, we summarized the complex network of interactions within the brain–liver–gut axis, encompassing the vagus nerve, barrier permeability, immunity and inflammation, the blood–brain barrier, gut microbial metabolites, the gut barrier, neurotoxic metabolites, and beta-amyloid (Aβ) metabolism. We also elaborated on the impact of the brain–liver–gut axis on various neurological disorders. Furthermore, we outline several therapies aimed at modulating the brain–liver–gut axis, including antibiotics, probiotics and prebiotics, fecal microbiota transplantation (FMT), vagus nerve stimulation (VNS), and dietary interventions. The focus is on elucidating possible mechanisms underlying neurological disorders pathogenesis and identifying effective treatments that are based on our understanding of the brain–liver–gut axis.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"21 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375368","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}
Severe trauma is often complicated by subsequent infection and organ dysfunction, with sepsis being a major mortality risk factor. Factors such as barrier destruction, wound contamination, invasive procedures, injury severity, and shock were traditionally considered primary predisposing elements for post-trauma sepsis. However, recent advances in stress biology have revealed a more nuanced understanding of the body's response to trauma. Organisms have evolved adaptive responses to various noxious stimuli that follow a biphasic pattern: Low to moderate stress levels can increase resilience, while overwhelming insults, both acute and chronic, overstrain the body’s coping mechanisms and are known as allostatic overload, hallmarked by maladaptive responses. An illustrative example of this concept is the body's response to iron ion exposure following trauma, transfusion, or haemolysis. Iron ions, at low levels, induce adaptive Nrf2-dependent responses, such as haem oxygenase gene expression. However, high concentrations or prolonged exposure can lead to cellular damage and organ failure, e.g. through the production of highly reactive free radicals. This biphasic pattern highlights the complex interplay between protective and harmful responses in post-trauma physiology. Whereas tools such as the SOFA score allow to measure severity of organ dysfunction, no metrics for quantifying the intensity of "stress" over time are available. As cumulative stress is a crucial outcome-associated factor in trauma care, the development of adequate indicators could significantly enhance our understanding and management of post-trauma complications, arising from secondary surgical interventions, transfusion management or metabolic derangements. This evolving perspective on stress biology in the severely injured host underscores the need for a more comprehensive approach to patient assessment and treatment in critical care settings, to identify and to decrease stress load with the aim to prevent life-threatening complications, such as sepsis, and ultimately improve outcomes.
{"title":"Sepsis after Trauma—Evolving Paradigms in Stress Biology and Host Response Failure","authors":"Petra Dickmann, Ralf A Claus, Michael Bauer","doi":"10.1093/burnst/tkaf014","DOIUrl":"https://doi.org/10.1093/burnst/tkaf014","url":null,"abstract":"Severe trauma is often complicated by subsequent infection and organ dysfunction, with sepsis being a major mortality risk factor. Factors such as barrier destruction, wound contamination, invasive procedures, injury severity, and shock were traditionally considered primary predisposing elements for post-trauma sepsis. However, recent advances in stress biology have revealed a more nuanced understanding of the body's response to trauma. Organisms have evolved adaptive responses to various noxious stimuli that follow a biphasic pattern: Low to moderate stress levels can increase resilience, while overwhelming insults, both acute and chronic, overstrain the body’s coping mechanisms and are known as allostatic overload, hallmarked by maladaptive responses. An illustrative example of this concept is the body's response to iron ion exposure following trauma, transfusion, or haemolysis. Iron ions, at low levels, induce adaptive Nrf2-dependent responses, such as haem oxygenase gene expression. However, high concentrations or prolonged exposure can lead to cellular damage and organ failure, e.g. through the production of highly reactive free radicals. This biphasic pattern highlights the complex interplay between protective and harmful responses in post-trauma physiology. Whereas tools such as the SOFA score allow to measure severity of organ dysfunction, no metrics for quantifying the intensity of \"stress\" over time are available. As cumulative stress is a crucial outcome-associated factor in trauma care, the development of adequate indicators could significantly enhance our understanding and management of post-trauma complications, arising from secondary surgical interventions, transfusion management or metabolic derangements. This evolving perspective on stress biology in the severely injured host underscores the need for a more comprehensive approach to patient assessment and treatment in critical care settings, to identify and to decrease stress load with the aim to prevent life-threatening complications, such as sepsis, and ultimately improve outcomes.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"9 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371516","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}
Kang Huang, Bobin Mi, Yuan Xiong, Zicai Fu, Wenyun Zhou, Wanjun Liu, Guohui Liu, Guandong Dai
Diabetes mellitus, a pervasive chronic metabolic disorder, is often associated with complications such as impaired wound healing. Various factors, most notably vascular deficiency, govern the wound repair process in diabetic patients, significantly impeding diabetic wound healing; therefore, angiogenesis and its role in diabetic wound repair have emerged as important areas of research. This review aims to delve into the mechanisms of angiogenesis, the effects of diabetes on angiogenesis, and the association between angiogenesis and diabetic wound repair. This will ultimately offer valuable guidance regarding the ideal timing of diabetic wound treatment in a clinical setting.
{"title":"Angiogenesis during diabetic wound repair: from mechanism to therapy opportunity","authors":"Kang Huang, Bobin Mi, Yuan Xiong, Zicai Fu, Wenyun Zhou, Wanjun Liu, Guohui Liu, Guandong Dai","doi":"10.1093/burnst/tkae052","DOIUrl":"https://doi.org/10.1093/burnst/tkae052","url":null,"abstract":"Diabetes mellitus, a pervasive chronic metabolic disorder, is often associated with complications such as impaired wound healing. Various factors, most notably vascular deficiency, govern the wound repair process in diabetic patients, significantly impeding diabetic wound healing; therefore, angiogenesis and its role in diabetic wound repair have emerged as important areas of research. This review aims to delve into the mechanisms of angiogenesis, the effects of diabetes on angiogenesis, and the association between angiogenesis and diabetic wound repair. This will ultimately offer valuable guidance regarding the ideal timing of diabetic wound treatment in a clinical setting.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"59 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367374","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 diabetic foot ulcer is among the most serious diabetes-associated complications, with a long disease course considerably increasing the pain and economic burden of patients, leading to amputation and even death. High blood sugar is characteristic of diabetic foot ulcers, with insufficient blood supply, oxidative stress disorder, and high-risk bacterial infection posing great challenges for disease treatment. Advances in hydrogel dressings have shown potential for the management of diabetic foot ulcers involving multisystem lesions. This study comprehensively reviews the pathogenesis of diabetic foot ulcers and advances in hydrogel dressings in treating diabetic foot ulcers, providing innovative perspectives for assessing the nursing care requirements and associated clinical applications.
{"title":"Hydrogel-based therapies for diabetic foot ulcers: recent developments and clinical implications.","authors":"Shuao Zhao, Xinyu Hu, Yiwen Zhao, Yige Zhang, Yesheng Jin, Fei Hua, Yong Xu, Wenge Ding","doi":"10.1093/burnst/tkae084","DOIUrl":"10.1093/burnst/tkae084","url":null,"abstract":"<p><p>The diabetic foot ulcer is among the most serious diabetes-associated complications, with a long disease course considerably increasing the pain and economic burden of patients, leading to amputation and even death. High blood sugar is characteristic of diabetic foot ulcers, with insufficient blood supply, oxidative stress disorder, and high-risk bacterial infection posing great challenges for disease treatment. Advances in hydrogel dressings have shown potential for the management of diabetic foot ulcers involving multisystem lesions. This study comprehensively reviews the pathogenesis of diabetic foot ulcers and advances in hydrogel dressings in treating diabetic foot ulcers, providing innovative perspectives for assessing the nursing care requirements and associated clinical applications.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"13 ","pages":"tkae084"},"PeriodicalIF":6.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363684","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}
The skin, the human body’s largest organ, is perpetually exposed to environmental factors, rendering it vulnerable to potential injuries. Fascia, a vital connective tissue that is extensively distributed throughout the body, fulfils multiple functions, including support, compartmentalization, and force transmission. The role of fascia in skin wound healing has recently attracted considerable attention. In addition to providing mechanical support, fascia significantly contributes to intercellular signalling and tissue repair, establishing itself as a crucial participant in wound healing. This review synthesises the latest advancements in fascia research and its implications for skin wound healing.
{"title":"Research progress on the role of fascia in skin wound healing","authors":"Jiamin Xu, Hongyan Zhang, Haifeng Ye","doi":"10.1093/burnst/tkaf002","DOIUrl":"https://doi.org/10.1093/burnst/tkaf002","url":null,"abstract":"The skin, the human body’s largest organ, is perpetually exposed to environmental factors, rendering it vulnerable to potential injuries. Fascia, a vital connective tissue that is extensively distributed throughout the body, fulfils multiple functions, including support, compartmentalization, and force transmission. The role of fascia in skin wound healing has recently attracted considerable attention. In addition to providing mechanical support, fascia significantly contributes to intercellular signalling and tissue repair, establishing itself as a crucial participant in wound healing. This review synthesises the latest advancements in fascia research and its implications for skin wound healing.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"53 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071587","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 Non-thyroidal illness syndrome is commonly observed in critically ill patients, characterized by the inactivation of systemic thyroid hormones (TH), which aggravates metabolic dysfunction. Recent evidence indicates that enhanced TH inactivation is mediated by the reactivation of type 3 deiodinase (Dio3) at the tissue level, culminating in a perturbed local metabolic equilibrium. This study assessed whether targeted inhibition of Dio3 can maintain tissue metabolic homeostasis under septic conditions and explored the mechanism behind Dio3 reactivation. Methods A retrospective clinical study was conducted to investigate the attributes of rT3. The expression of Dio3 was detected by immunoblotting, immunofluorescence, and immunohistochemical staining in tissues extracted from CLP-induced septic rats and human biopsy samples. In addition, the effect of Dio3 inhibition on skeletal muscle metabolism was observed in rats with targeted Dio3 knockdown using an adeno-associated virus. The effectiveness of Sonic hedgehog (Shh) signaling inhibition on systemic TH levels was observed in CLP-induced septic rats receiving cyclopamine. The mechanisms underlying such inhibition were explored using immunoblotting, RNA-seq, and chromatin immunoprecipitation–qPCR assays. Results The main product of Dio3, rT3, is strongly associated with organ function. Early sepsis leads to significant upregulation of Dio3 in the skeletal muscles and lung tissues of septic rats. The targeted inhibition of Dio3 in skeletal muscle restores TH responsiveness, prevents fast-to-slow fiber conversion, preserves glucose transporter type 4 functionality, and maintains metabolic balance between protein synthesis and proteolysis, which leads to preserved muscle mass. The reactivation of Dio3 is transcriptionally regulated by the Shh pathway induced by the signal transducer and activator of transcription 3. Conclusions The suppression of Dio3 restores tissue TH actions, attenuates proteolysis, and ameliorates anabolic resistance in the skeletal muscles of septic rats, thereby improving local metabolic homeostasis. Our results provide insights into the mechanisms of Dio3 reactivation and its critical role in local metabolic alterations induced by sepsis, while also suggesting novel targets aimed at ameliorating tissue-specific metabolic disorders.
{"title":"Type 3 deiodinase activation mediated by the Shh/Gli1 axis promotes sepsis-induced metabolic dysregulation in skeletal muscles","authors":"Gang Wang, Tao Gao, Yijiang Liu, Jianfeng Duan, Huimin Lu, Anqi Jiang, Yun Xu, Xiaolan Lu, Xiaoyao Li, Yong Wang, Wenkui Yu","doi":"10.1093/burnst/tkae066","DOIUrl":"https://doi.org/10.1093/burnst/tkae066","url":null,"abstract":"Background Non-thyroidal illness syndrome is commonly observed in critically ill patients, characterized by the inactivation of systemic thyroid hormones (TH), which aggravates metabolic dysfunction. Recent evidence indicates that enhanced TH inactivation is mediated by the reactivation of type 3 deiodinase (Dio3) at the tissue level, culminating in a perturbed local metabolic equilibrium. This study assessed whether targeted inhibition of Dio3 can maintain tissue metabolic homeostasis under septic conditions and explored the mechanism behind Dio3 reactivation. Methods A retrospective clinical study was conducted to investigate the attributes of rT3. The expression of Dio3 was detected by immunoblotting, immunofluorescence, and immunohistochemical staining in tissues extracted from CLP-induced septic rats and human biopsy samples. In addition, the effect of Dio3 inhibition on skeletal muscle metabolism was observed in rats with targeted Dio3 knockdown using an adeno-associated virus. The effectiveness of Sonic hedgehog (Shh) signaling inhibition on systemic TH levels was observed in CLP-induced septic rats receiving cyclopamine. The mechanisms underlying such inhibition were explored using immunoblotting, RNA-seq, and chromatin immunoprecipitation–qPCR assays. Results The main product of Dio3, rT3, is strongly associated with organ function. Early sepsis leads to significant upregulation of Dio3 in the skeletal muscles and lung tissues of septic rats. The targeted inhibition of Dio3 in skeletal muscle restores TH responsiveness, prevents fast-to-slow fiber conversion, preserves glucose transporter type 4 functionality, and maintains metabolic balance between protein synthesis and proteolysis, which leads to preserved muscle mass. The reactivation of Dio3 is transcriptionally regulated by the Shh pathway induced by the signal transducer and activator of transcription 3. Conclusions The suppression of Dio3 restores tissue TH actions, attenuates proteolysis, and ameliorates anabolic resistance in the skeletal muscles of septic rats, thereby improving local metabolic homeostasis. Our results provide insights into the mechanisms of Dio3 reactivation and its critical role in local metabolic alterations induced by sepsis, while also suggesting novel targets aimed at ameliorating tissue-specific metabolic disorders.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"20 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054856","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 Diabetic wounds pose significant clinical challenges due to impaired healing processes, often resulting in chronic, non-healing ulcers. Asiaticoside (AC), a natural triterpene derivative from Centella asiatica, has demonstrated notable anti-inflammatory and wound-healing properties. However, the synergistic effects of nitric oxide (NO)—a recognized promoter of wound healing—combined with AC in treating diabetic wounds remain inadequately explored. Methods Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds. Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets. The effects of Asiaticoside-nitric oxide hydrogel (ACNO) on gene and protein expression were evaluated using RT-qPCR and western blotting. In vitro experiments using SRC agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC, STAT3, and other proteins in HaCaT cells. Results Metabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation, which was attenuated by ACNO treatment. Key metabolites modulated by ACNO included mandelic acid, lactic acid, and 3-hydroxyisovaleric acid. The primary metabolic pathways involved were methyl histidine metabolism and the malate–aspartate shuttle. Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis, promoted cellular proliferation, and facilitated diabetic wound closure. RT–qPCR data demonstrated that ACNO regulated the transcription of critical genes (SRC, STAT3, EGFR, and VEGFA). Notably, ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression. Conclusions These findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis. By correlating altered metabolites with molecular targets, this study elucidates the pharmacodynamic foundation for ACNO’s pre-clinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.
{"title":"Asiaticoside-nitric oxide synergistically accelerate diabetic wound healing by regulating key metabolites and SRC/STAT3 signaling","authors":"Xingrui Mu, Jitao Chen, Huan Zhu, Junyu Deng, Xingqian Wu, Wenjie He, Penghui Ye, Rifang Gu, Youzhi Wu, Felicity Han, Xuqiang Nie","doi":"10.1093/burnst/tkaf009","DOIUrl":"https://doi.org/10.1093/burnst/tkaf009","url":null,"abstract":"Background Diabetic wounds pose significant clinical challenges due to impaired healing processes, often resulting in chronic, non-healing ulcers. Asiaticoside (AC), a natural triterpene derivative from Centella asiatica, has demonstrated notable anti-inflammatory and wound-healing properties. However, the synergistic effects of nitric oxide (NO)—a recognized promoter of wound healing—combined with AC in treating diabetic wounds remain inadequately explored. Methods Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds. Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets. The effects of Asiaticoside-nitric oxide hydrogel (ACNO) on gene and protein expression were evaluated using RT-qPCR and western blotting. In vitro experiments using SRC agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC, STAT3, and other proteins in HaCaT cells. Results Metabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation, which was attenuated by ACNO treatment. Key metabolites modulated by ACNO included mandelic acid, lactic acid, and 3-hydroxyisovaleric acid. The primary metabolic pathways involved were methyl histidine metabolism and the malate–aspartate shuttle. Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis, promoted cellular proliferation, and facilitated diabetic wound closure. RT–qPCR data demonstrated that ACNO regulated the transcription of critical genes (SRC, STAT3, EGFR, and VEGFA). Notably, ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression. Conclusions These findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis. By correlating altered metabolites with molecular targets, this study elucidates the pharmacodynamic foundation for ACNO’s pre-clinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"2 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049741","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}
Abdullah Al Mamun, Chuxiao Shao, Peiwu Geng, Shuanghu Wang, Jian Xiao
Neuroregulation during skin wound healing involves complex interactions between the nervous system and intricate tissue repair processes. The skin, the largest organ, depends on a complex system of nerves to manage responses to injury. Recent research has emphasized the crucial role of neuroregulation in maximizing wound healing outcomes. Recently, researchers have also explained the interactive contact between the peripheral nervous system and skin cells during the different phases of wound healing. Neurotransmitters and neuropeptides, once observed as simple signalling molecules, have since been recognized as effective regulators of inflammation, angiogenesis, and cell proliferation. The significance of skin innervation and neuromodulators is underscored by the delayed wound healing observed in patients with diabetes and the regenerative capabilities of foetal skin. Foetal skin regeneration is influenced by the neuroregulatory environment, immature immune system, abundant growth factors, and increased pluripotency of cells. Foetal skin cells exhibit greater flexibility and specialized cell types, and the extracellular matrix composition promotes regeneration. The extracellular matrix composition of foetal skin promotes regeneration, making it more capable than adult skin because neuroregulatory signals affect skin regeneration. The understanding of these systems can facilitate the development of therapeutic strategies to alter the nerve supply to the skin to enhance the process of wound healing. Neuroregulation is being explored as a potential therapeutic strategy for enhancing skin wound repair. Bioelectronic strategies and neuromodulation techniques can manipulate neural signalling, optimize the neuroimmune axis, and modulate inflammation. This review describes the function of skin innervation in wound healing, emphasizing the importance of neuropeptides released by sensory and autonomic nerve fibres. This article discusses significant discoveries related to neuroregulation and its impact on skin wound healing.
{"title":"Recent advances in the role of neuroregulation in skin wound healing","authors":"Abdullah Al Mamun, Chuxiao Shao, Peiwu Geng, Shuanghu Wang, Jian Xiao","doi":"10.1093/burnst/tkae072","DOIUrl":"https://doi.org/10.1093/burnst/tkae072","url":null,"abstract":"Neuroregulation during skin wound healing involves complex interactions between the nervous system and intricate tissue repair processes. The skin, the largest organ, depends on a complex system of nerves to manage responses to injury. Recent research has emphasized the crucial role of neuroregulation in maximizing wound healing outcomes. Recently, researchers have also explained the interactive contact between the peripheral nervous system and skin cells during the different phases of wound healing. Neurotransmitters and neuropeptides, once observed as simple signalling molecules, have since been recognized as effective regulators of inflammation, angiogenesis, and cell proliferation. The significance of skin innervation and neuromodulators is underscored by the delayed wound healing observed in patients with diabetes and the regenerative capabilities of foetal skin. Foetal skin regeneration is influenced by the neuroregulatory environment, immature immune system, abundant growth factors, and increased pluripotency of cells. Foetal skin cells exhibit greater flexibility and specialized cell types, and the extracellular matrix composition promotes regeneration. The extracellular matrix composition of foetal skin promotes regeneration, making it more capable than adult skin because neuroregulatory signals affect skin regeneration. The understanding of these systems can facilitate the development of therapeutic strategies to alter the nerve supply to the skin to enhance the process of wound healing. Neuroregulation is being explored as a potential therapeutic strategy for enhancing skin wound repair. Bioelectronic strategies and neuromodulation techniques can manipulate neural signalling, optimize the neuroimmune axis, and modulate inflammation. This review describes the function of skin innervation in wound healing, emphasizing the importance of neuropeptides released by sensory and autonomic nerve fibres. This article discusses significant discoveries related to neuroregulation and its impact on skin wound healing.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049740","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}
Objective Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly impairs muscle regeneration following injuries, contributing to numerous complications and reduced quality of life. There is an urgent need for therapeutic strategies that can enhance muscle regeneration and alleviate these pathological mechanisms. In this study, we evaluate the therapeutic efficacy of W-GA nanodots, which are composed of gallic acid (GA) and tungstate (W6+), on muscle regeneration in type 2 diabetes mellitus (T2D)-induced muscle injury, with a focus on their anti-inflammatory and antioxidative effects. Methods This study synthesized ultrasmall W-GA nanodots that were optimized for improved stability and bioactivity under physiological conditions. In vitro assessments included cell viability, apoptosis, reactive oxygen species (ROS) generation, and myotube differentiation in C2C12 myoblasts under hyperglycemic conditions. In vivo, T2D was induced in C57BL/6 mice, followed by muscle injury and treatment with W-GA. Muscle repair, fibrosis, and functional recovery were assessed through histological analysis and gait analysis using the CatWalk system. Results The W-GA nanodots significantly enhanced muscle cell proliferation, decreased ROS, and reduced apoptosis in vitro. In vivo, compared with the control group, the W-GA-treated group exhibited notably improved muscle regeneration, decreased fibrosis, and enhanced functional recovery. The treatment notably modulated the inflammatory response and oxidative stress in diabetic muscle tissues, facilitating improved regenerative dynamics and muscle function. Conclusions W-GA nanodots effectively counter the pathological mechanisms of diabetic myopathy by enhancing regenerative capacity and reducing oxidative stress and inflammation. This nanomedicine approach offers a promising therapeutic avenue for improving muscle health and overall quality of life in individuals suffering from T2D. However, further studies are needed to explore the clinical applications and long-term efficacy of these nanodots in preventing diabetic complications.
{"title":"Enhancing diabetic muscle repair through W-GA nanodots: a nanomedicinal approach to ameliorate myopathy in type 2 diabetes","authors":"Shan Liu, Renwen Wan, QingRong Li, Yisheng Chen, Yanwei He, Xingting Feng, Patrick Shu-Hang Yung, Zhiwen Luo, Xianwen Wang, Chen Chen","doi":"10.1093/burnst/tkae059","DOIUrl":"https://doi.org/10.1093/burnst/tkae059","url":null,"abstract":"Objective Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly impairs muscle regeneration following injuries, contributing to numerous complications and reduced quality of life. There is an urgent need for therapeutic strategies that can enhance muscle regeneration and alleviate these pathological mechanisms. In this study, we evaluate the therapeutic efficacy of W-GA nanodots, which are composed of gallic acid (GA) and tungstate (W6+), on muscle regeneration in type 2 diabetes mellitus (T2D)-induced muscle injury, with a focus on their anti-inflammatory and antioxidative effects. Methods This study synthesized ultrasmall W-GA nanodots that were optimized for improved stability and bioactivity under physiological conditions. In vitro assessments included cell viability, apoptosis, reactive oxygen species (ROS) generation, and myotube differentiation in C2C12 myoblasts under hyperglycemic conditions. In vivo, T2D was induced in C57BL/6 mice, followed by muscle injury and treatment with W-GA. Muscle repair, fibrosis, and functional recovery were assessed through histological analysis and gait analysis using the CatWalk system. Results The W-GA nanodots significantly enhanced muscle cell proliferation, decreased ROS, and reduced apoptosis in vitro. In vivo, compared with the control group, the W-GA-treated group exhibited notably improved muscle regeneration, decreased fibrosis, and enhanced functional recovery. The treatment notably modulated the inflammatory response and oxidative stress in diabetic muscle tissues, facilitating improved regenerative dynamics and muscle function. Conclusions W-GA nanodots effectively counter the pathological mechanisms of diabetic myopathy by enhancing regenerative capacity and reducing oxidative stress and inflammation. This nanomedicine approach offers a promising therapeutic avenue for improving muscle health and overall quality of life in individuals suffering from T2D. However, further studies are needed to explore the clinical applications and long-term efficacy of these nanodots in preventing diabetic complications.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"61 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027227","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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