Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin r...Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin regeneration during expansion.S100 calcium-binding protein A9(S100A9)is essential in promoting wound healing;however,its effects on skin regeneration during tissue expansion remain unclear.The aim of the present study was to explore the role of S100A9 in skin regeneration,particularly collagen production to investigate its importance in skin regeneration during tissue expansion.Methods:The expression and distribution of S100A9 and its receptors-toll-like receptor 4(TLR-4)and receptor for advanced glycation end products were studied in expanded skin.These character-istics were investigated in skin samples of rats and patients.Moreover,the expression of S100A9 was investigated in stretched keratinocytes in vitro.The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed.TAK-242 was used to inhibit the binding of S100A9 to TLR-4;the levels of collagen I(COL I),transforming growth factor beta(TGF-β),TLR-4 and phospho-extracellular signal-related kinase 1/2(p-ERK1/2)in fibroblasts were determined.Furthermore,fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I,TGF-β,TLR-4 and p-ERK1/2 in fibroblasts were investigated.Additionally,the area of expanded skin,thickness of the dermis,and synthesis of COL I,TGF-β,TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.Results:Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix(ECM)in the expanded dermis.Furthermore,S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-βin fibroblasts via the TLR-4/ERK1/2 pathway.We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I,TGF-β,TLR-4 and p-ERK1/2 expression in skin fibroblasts.Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.Conclusions:These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression.Our study laid the foundation for clinically improving tissue expansion using S100A9.展开更多
CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozy...CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozygous mutants of the insulin receptor gene 2(NlInR2)in the brown planthopper(Nilaparvata lugens)using CRISPR/Cas9 genome editing.Both frameshift mutants,E5_D17 and E6_I7,differentiated towards long wings,but there were differences in wing morphology,with E5_D17 showing wing deformities.Subsequent investigations revealed the presence of residual expression of NlInR2 mRNA in both mutants,as well as the occurrence of spliceosomes featuring exon skipping splicing in E5_D17.Additionally,the E5_D17 exhibited the detection of N-terminally truncated NlInR2 protein.RNA interference experiments indicated that the knockdown of NlInR2 expression in the E5_D17 mutant line increased the proportion of wing deformities from 11.1 to 65.6%,suggesting that the residual NlInR2 mRNA of the E5_D17 mutant might have retained some genetic functions.Our results imply that systematic characterization of residual protein expression or function in CRISPR/Cas9-generated mutant lines is necessary for phenotypic interpretation.展开更多
目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例...目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例)和对照组(未继发AE,165例)。多因素Logistic回归分析HSV感染患者继发AE的独立影响因素。Spearman法分析脑脊液中Cys-C、MMP-9与S100B水平的相关性。受试者工作特征(ROC)曲线分析S100B、Cys-C、MMP-9对AE的预测价值。构建风险预测模型并进行评价。结果:多因素Logistic回归分析显示,MRI异常、脑脊液S100B、MMP-9升高、EEG异常是HSV感染患者继发AE的独立危险因素,脑脊液Cys-C是其保护因素(P<0.05)。Spearman分析显示,HSV感染患者Cys-C浓度与S100B水平呈负相关(r=-0.83,P<0.05),MMP-9浓度与S100B水平呈正相关(r=0.88,P<0.05)。构建的联合预测因子pre1诊断HSV患者继发AE的AUC明显大于S100B、Cys-C、MMP-9单独预测的AUC(0.876 vs 0.827、0.787、0.750)。构建的风险预测模型具有良好的区分度和一致性。结论:脑脊液中S100B、Cys-C、MMP-9水平均可对HSV感染患者诱发AE的可能性进行有效预测,且三项指标联合预测价值最大,其次是S100B蛋白、Cys-C、MMP-9。展开更多
基金supported by grants from the Natural Science Foundation of China(81971851 and 82172229)the Natural Science Foundation of Shaanxi Province(2022JM-600)the Foundation of Xijing Hospital Grants(XJZT21CM33).
文摘Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin regeneration during expansion.S100 calcium-binding protein A9(S100A9)is essential in promoting wound healing;however,its effects on skin regeneration during tissue expansion remain unclear.The aim of the present study was to explore the role of S100A9 in skin regeneration,particularly collagen production to investigate its importance in skin regeneration during tissue expansion.Methods:The expression and distribution of S100A9 and its receptors-toll-like receptor 4(TLR-4)and receptor for advanced glycation end products were studied in expanded skin.These character-istics were investigated in skin samples of rats and patients.Moreover,the expression of S100A9 was investigated in stretched keratinocytes in vitro.The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed.TAK-242 was used to inhibit the binding of S100A9 to TLR-4;the levels of collagen I(COL I),transforming growth factor beta(TGF-β),TLR-4 and phospho-extracellular signal-related kinase 1/2(p-ERK1/2)in fibroblasts were determined.Furthermore,fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I,TGF-β,TLR-4 and p-ERK1/2 in fibroblasts were investigated.Additionally,the area of expanded skin,thickness of the dermis,and synthesis of COL I,TGF-β,TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.Results:Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix(ECM)in the expanded dermis.Furthermore,S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-βin fibroblasts via the TLR-4/ERK1/2 pathway.We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I,TGF-β,TLR-4 and p-ERK1/2 expression in skin fibroblasts.Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.Conclusions:These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression.Our study laid the foundation for clinically improving tissue expansion using S100A9.
基金the National Natural Science Foundation of China(31730073).
文摘CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozygous mutants of the insulin receptor gene 2(NlInR2)in the brown planthopper(Nilaparvata lugens)using CRISPR/Cas9 genome editing.Both frameshift mutants,E5_D17 and E6_I7,differentiated towards long wings,but there were differences in wing morphology,with E5_D17 showing wing deformities.Subsequent investigations revealed the presence of residual expression of NlInR2 mRNA in both mutants,as well as the occurrence of spliceosomes featuring exon skipping splicing in E5_D17.Additionally,the E5_D17 exhibited the detection of N-terminally truncated NlInR2 protein.RNA interference experiments indicated that the knockdown of NlInR2 expression in the E5_D17 mutant line increased the proportion of wing deformities from 11.1 to 65.6%,suggesting that the residual NlInR2 mRNA of the E5_D17 mutant might have retained some genetic functions.Our results imply that systematic characterization of residual protein expression or function in CRISPR/Cas9-generated mutant lines is necessary for phenotypic interpretation.
文摘目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例)和对照组(未继发AE,165例)。多因素Logistic回归分析HSV感染患者继发AE的独立影响因素。Spearman法分析脑脊液中Cys-C、MMP-9与S100B水平的相关性。受试者工作特征(ROC)曲线分析S100B、Cys-C、MMP-9对AE的预测价值。构建风险预测模型并进行评价。结果:多因素Logistic回归分析显示,MRI异常、脑脊液S100B、MMP-9升高、EEG异常是HSV感染患者继发AE的独立危险因素,脑脊液Cys-C是其保护因素(P<0.05)。Spearman分析显示,HSV感染患者Cys-C浓度与S100B水平呈负相关(r=-0.83,P<0.05),MMP-9浓度与S100B水平呈正相关(r=0.88,P<0.05)。构建的联合预测因子pre1诊断HSV患者继发AE的AUC明显大于S100B、Cys-C、MMP-9单独预测的AUC(0.876 vs 0.827、0.787、0.750)。构建的风险预测模型具有良好的区分度和一致性。结论:脑脊液中S100B、Cys-C、MMP-9水平均可对HSV感染患者诱发AE的可能性进行有效预测,且三项指标联合预测价值最大,其次是S100B蛋白、Cys-C、MMP-9。
