目的:探讨序贯激光结合^(32)P同位素敷贴协同治疗烧伤增生性瘢痕的疗效及对瘢痕组织TGF-β_(1)、BMP-7的影响。方法:选择2021年3月-2023年3月在笔者医院收治的124例烧伤增生性瘢痕患者,随机分为对照组和观察组,每组62例。对照组患者均...目的:探讨序贯激光结合^(32)P同位素敷贴协同治疗烧伤增生性瘢痕的疗效及对瘢痕组织TGF-β_(1)、BMP-7的影响。方法:选择2021年3月-2023年3月在笔者医院收治的124例烧伤增生性瘢痕患者,随机分为对照组和观察组,每组62例。对照组患者均予以序贯激光治疗,观察组在接受激光治疗后给予^(32)P同位素敷贴。比较两组患者的总有效率、瘙痒视觉模拟评分(VAS)、温哥华瘢痕量表(Vancouver scar scale,VSS)评分、简明健康状况调查量表(Short form 36 health survey,SF-36)评分、监测瘢痕组织中TGF-β_(1)、BMP-7水平及不良反应发生情况。随访6个月,观察两组患者的复发率。结果:末次治疗后,观察组患者的总有效率、SF-36评分均高于对照组(P<0.05);观察组患者的VAS评分、VSS评分均低于对照组(P<0.05);观察组患者的TGF-β_(1)水平低于对照组,BMP-7水平高于对照组(P<0.05)。两组患者在不良反应发生率方面差异无统计学意义(P>0.05)。随访6个月后,观察组患者的复发率低于对照组(P<0.05)。结论:序贯激光结合^(32)P同位素敷贴协同治疗烧伤后增生性瘢痕能够有效改善患者的临床症状和生活质量,降低复发风险,同时能够调节TGF-β_(1)和BMP-7在瘢痕形成过程中的平衡,抑制成纤维细胞增殖和胶原沉积。展开更多
Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represe...Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats.This adaptation has been hypothesized to result,in part,from the inhibition of interphalangeal cell apoptosis during limb development,although the underlying genetic mechanism remains poorly understood.This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes,BMP2,BMP4,and BMP7,which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues.Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage,with two positively selected sites(V79I and H247R)involved in cetacean-specific amino acid substitutions located in the TGF-βpropeptide functional domain in BMP4.In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors,including cytochrome c(Cyt c),BCL2 associated X,and B-cell lymphoma 2,within the BMP signaling pathway.The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.展开更多
Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators...Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators of cortical astrocyte maturation.We demonstrate that Olig1 and Olig2 work synergistically to regulate cortical astrocyte maturation by modulating Bmp7 expression.Genetic ablation of both Olig1 and Olig2 results in defective astrocyte morphology,including reduced process complexity and an immature gene expression profile.Single-cell RNA sequencing reveals a shift towards a less mature astrocyte state,marked by elevated levels of HOPX and GFAP,resembling human astrocytes.Mechanistically,Olig1 and Olig2 bind directly to the Bmp7 enhancer,repressing its expression to promote astrocyte maturation.Overexpression of Bmp7 in vivo replicates the astrocyte defects seen in Olig1/2 double mutants,confirming the critical role of BMP7 signaling in this process.These findings provide insights into the transcriptional and signaling pathways regulating astrocyte development and highlight Olig1 and Olig2 as key regulators of cortical astrocyte maturation,with potential implications for understanding glial dysfunction in neurological diseases.展开更多
文摘目的:探讨序贯激光结合^(32)P同位素敷贴协同治疗烧伤增生性瘢痕的疗效及对瘢痕组织TGF-β_(1)、BMP-7的影响。方法:选择2021年3月-2023年3月在笔者医院收治的124例烧伤增生性瘢痕患者,随机分为对照组和观察组,每组62例。对照组患者均予以序贯激光治疗,观察组在接受激光治疗后给予^(32)P同位素敷贴。比较两组患者的总有效率、瘙痒视觉模拟评分(VAS)、温哥华瘢痕量表(Vancouver scar scale,VSS)评分、简明健康状况调查量表(Short form 36 health survey,SF-36)评分、监测瘢痕组织中TGF-β_(1)、BMP-7水平及不良反应发生情况。随访6个月,观察两组患者的复发率。结果:末次治疗后,观察组患者的总有效率、SF-36评分均高于对照组(P<0.05);观察组患者的VAS评分、VSS评分均低于对照组(P<0.05);观察组患者的TGF-β_(1)水平低于对照组,BMP-7水平高于对照组(P<0.05)。两组患者在不良反应发生率方面差异无统计学意义(P>0.05)。随访6个月后,观察组患者的复发率低于对照组(P<0.05)。结论:序贯激光结合^(32)P同位素敷贴协同治疗烧伤后增生性瘢痕能够有效改善患者的临床症状和生活质量,降低复发风险,同时能够调节TGF-β_(1)和BMP-7在瘢痕形成过程中的平衡,抑制成纤维细胞增殖和胶原沉积。
基金supported by the National Key Programme of Research and Development,Ministry of Science and Technology of China(2022YFF1301600)National Natural Science Foundation of China(32030011,U24A20362,32070409)+2 种基金PI Project of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(GML2021 GD0805)Qing Lan Project of Jiangsu ProvincePriority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats.This adaptation has been hypothesized to result,in part,from the inhibition of interphalangeal cell apoptosis during limb development,although the underlying genetic mechanism remains poorly understood.This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes,BMP2,BMP4,and BMP7,which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues.Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage,with two positively selected sites(V79I and H247R)involved in cetacean-specific amino acid substitutions located in the TGF-βpropeptide functional domain in BMP4.In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors,including cytochrome c(Cyt c),BCL2 associated X,and B-cell lymphoma 2,within the BMP signaling pathway.The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.
基金supported by the National Natural Science Foundation of China(82271197,81974175,31820103006,32070971,32200792,32200776).
文摘Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators of cortical astrocyte maturation.We demonstrate that Olig1 and Olig2 work synergistically to regulate cortical astrocyte maturation by modulating Bmp7 expression.Genetic ablation of both Olig1 and Olig2 results in defective astrocyte morphology,including reduced process complexity and an immature gene expression profile.Single-cell RNA sequencing reveals a shift towards a less mature astrocyte state,marked by elevated levels of HOPX and GFAP,resembling human astrocytes.Mechanistically,Olig1 and Olig2 bind directly to the Bmp7 enhancer,repressing its expression to promote astrocyte maturation.Overexpression of Bmp7 in vivo replicates the astrocyte defects seen in Olig1/2 double mutants,confirming the critical role of BMP7 signaling in this process.These findings provide insights into the transcriptional and signaling pathways regulating astrocyte development and highlight Olig1 and Olig2 as key regulators of cortical astrocyte maturation,with potential implications for understanding glial dysfunction in neurological diseases.