Objective:This study aimed to investigate the association of atopic dermatitis(AD)and anxiety/depression behaviors induced by AD with the intestinal microbiota.Additionally,it sought to evaluate the therapeutic potent...Objective:This study aimed to investigate the association of atopic dermatitis(AD)and anxiety/depression behaviors induced by AD with the intestinal microbiota.Additionally,it sought to evaluate the therapeutic potential of mannan oligosaccharide(MOS)in alleviating AD symptoms through the modulation of the gut microbiota and the enhancement of short-chain fatty acids(SCFAs)production.Methods:Female Kunming mice were challenged with 2,4-dinitrofluorobenzene(DNFB)to induce AD-like symptoms.MOS was administered orally daily for 14 days.On the 6th and 11th days post-modeling,the number of scratching bouts in mice was recorded.Following dissection,epidermal thickness,mast cell infiltration,and serum levels of inflammatory cytokines were measured.Meanwhile,cerebral levels of neurotransmitters,including 5-hydroxytryptamine(5-HT)and norepinephrine(NE),were assessed.The abundance of intestinal microbiota and fecal concentrations of SCFAs were also analyzed.Results:MOS significantly reduced AD-like symptoms by reducing inflammatory cytokines,as reflected in a significant decrease in the number of scratching bouts,epidermal thickness,mast cells and inflammatory cytokine levels.MOS intervention up-regulated the expression of 5-HT and NE,and consequently alleviated anxiety and depression-like behaviors.Furthermore,compared with the AD group,MOS intervention increased the gut microbiota abundance of mice,especially beneficial bacteria such as Bifidobacterium,Lactobacillus and Klebsiella.At the same time,these beneficial bacteria significantly increased the fecal contents of SCFAs,especially propionic acid.Correlation analysis indicated that AD amelioration was positively correlated with fecal SCFAs levels and the proliferation of certain intestinal microbes.Conclusion:MOS intervention could offer a novel approach to managing AD and its psychological comorbidities.展开更多
Objective:To investigate the influence of xylooligosaccharides on skin inflammation,behavioral characteristics,neurotransmitters,and gut flora in a mouse model of atopic dermatitis(AD)induced by 2,4-dinitrofluorobenze...Objective:To investigate the influence of xylooligosaccharides on skin inflammation,behavioral characteristics,neurotransmitters,and gut flora in a mouse model of atopic dermatitis(AD)induced by 2,4-dinitrofluorobenzene(DNFB).Methods:The AD mouse model was created by administration of DNFB for 14 consecutive days.The scoring atopic dermatitis index,enzyme-linked immunosorbent assay(ELISA),histopathology,and immunohistochemical analyses were used to assess inflammation and depression-like behaviors.Furthermore,high-throughput 16S rRNA gene sequencing was used to determine the composition of fecal microbiota.Results:Xylooligosaccharides treatment reduced the number of scratches and skin thickness,mast cell infiltration and the levels of immunoglobulin(Ig)E and T-helper cytokines compared with the AD model group.Meanwhile,xylooligosaccharides treatment reduced the immobility time of mice in the forced swimming test and increased the total movement distance and movement distance in the center area in the open-field test.Furthermore,5-hydroxytryptamine and dopamine expression in the brain was increased following xylooligosaccharides treatment.Using network pharmacology,Gene Ontology analysis showed that the targets were mainly enriched in phosphatase binding and the regulation of leukocyte differentiation,which ameliorated AD mainly through the hypoxia inducible factor-1 and phosphatidylinositide 3-kinase-protein kinase B pathways.16S rRNA gene sequencing,diversity indices,and gut microbial taxonomic composition analysis showed DNFB-induced changes in intestinal microbiota diversity in AD mice.Comparative analysis indicated that xylooligosaccharides intake improved the gut microbiome by dramatically enhancing the concentration of Lactobacillus while decreasing the concentration of Bacteroides in mice.Conclusion:Xylooligosaccharides reduce inflammatory dermatosis and related depression-like behaviors via regulating intestinal homeostasis,having medicinal value as a nutritional and functional ingredient.展开更多
Aim The present study aimed to investigate anti-inflammatory activity of 6-AP on murine model of aller- gic contact dermatitis （ACD）. Methods 6＇-acetylpaeoniflorin （6-AP） was synthesized from paeoniflorin （Pae）...Aim The present study aimed to investigate anti-inflammatory activity of 6-AP on murine model of aller- gic contact dermatitis （ACD）. Methods 6＇-acetylpaeoniflorin （6-AP） was synthesized from paeoniflorin （Pae） via acetylation and the structure was characterized by 1H-NMR, 13C-NMR and EI-MS. ACD model was established by repeated application of dinitrochlorobenzene （DNCB） to induce skin immune inflammation. The mice were oral- ly administered 6-AP （35, 70, 140 mg. kg-1 ·d^-l）, Pae （70 rag. kg-1·d^-1） and prednisone （Pre, 5 rag. kg^- 1· d^-1 ） from day 1 to day 7 after Cutaneous inflammation was evaluated by ear swelling and histological exami- nation. Splenocyte proliferation was assayed by the 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyl-2H tetrazolium bromide assay. The cytokine production in the splenocytes was measured by enzyme-linked immunosorbent assay. Results Topical application of DNCB to the skin provoked obvious swelling and inflammatory cell infiltration. 6- AP significantly inhibited ear swelling, decreased inflammatory cell infiltration and epidermal keratinization. Ad- dtionally, 6-AP obviously alleviated the hyperplasia of red pulp and germinal center （GC） appearance, decreased spleen index, decreased spleen index, and inhibited splenocyte proliferation in ACD model, compared to that of Pae. Further, the study indicated that 6-AP treatment could increase IL-10 level, while reduce IL-17 level in splenocytes simultaneously. The correlation analysis displayed significantly positive correlations between IL-17 level and the severity of skin inflammation, while negative correlations between IL-10 level and skin inflammation. Con- clusion 6-AP has a significantly higher anti-inflammatory effect than Pae, and it may be a useful treatment for ACD.展开更多
目的探究凉血清肺汤联合硝黄搽剂湿敷治疗面部脂溢性皮炎肺胃热盛证的临床效果。方法回顾性选取2022年1月—2023年1月期间收治的面部脂溢性皮炎肺胃热盛证患者102例,根据随机数字表法分为研究组(51例),常规组(51例)。常规组进行硝黄搽...目的探究凉血清肺汤联合硝黄搽剂湿敷治疗面部脂溢性皮炎肺胃热盛证的临床效果。方法回顾性选取2022年1月—2023年1月期间收治的面部脂溢性皮炎肺胃热盛证患者102例,根据随机数字表法分为研究组(51例),常规组(51例)。常规组进行硝黄搽剂湿敷治疗,研究组采用凉血清肺汤联合硝黄搽剂湿敷治疗。比较治疗结束后患者临床疗效,比较治疗结束后患者湿疹面积及严重程度指数(eczema area severity index,EASI)、整体评分(investigator′s global assessment,IGA)、基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)、白细胞介素-1β(interleukin-1β,IL-1β)水平,并比较治疗期间的不良反应情况。结果治疗后,两组患者中医症状评分较治疗前均降低(P<0.05),且研究组低于常规组(P<0.05),研究组、常规组治疗总有效率分别为94.12%(48/51)、72.55%(37/51),研究组较常规组高(P<0.05),治疗后两组IGA、EASI评分降低,研究组较常规组低(P<0.05),两组面部脂溢性皮炎肺胃热盛证患者治疗后MMP-3、IL-1β水平降低,研究组MMP-3、IL-1β水平较常规组低(P<0.05),两组患者不良反应率比较,差异均无统计学意义(P>0.05)。结论凉血清肺汤联合硝黄搽剂湿敷能够提高面部脂溢性皮炎肺胃热盛证患者的临床疗效,缓解症状,降低IGA、EASI评分,改善血清炎症水平,安全性较高。展开更多
目的:观察度普利尤单抗治疗老年特应性皮炎(atopic dermatitis,AD)的疗效及安全性。方法:回顾性收集北京安贞医院皮肤性病科2021年1月至2023年10月收治的接受度普利尤单抗治疗至少16周的老年AD患者,比较治疗前、治疗期间以及治疗后的临...目的:观察度普利尤单抗治疗老年特应性皮炎(atopic dermatitis,AD)的疗效及安全性。方法:回顾性收集北京安贞医院皮肤性病科2021年1月至2023年10月收治的接受度普利尤单抗治疗至少16周的老年AD患者,比较治疗前、治疗期间以及治疗后的临床指标,包括瘙痒数字评价量表(pruritus numerical rating score,PNRS)、湿疹面积和严重程度指数(eczema area and severity index,EASI)、皮肤病生活质量指数(dermatology life quality index,DLQI),同时记录发生的不良反应;比较治疗前及治疗16周后外周血干扰素γ(interferon-γ,IFN-γ)、白细胞介素(interleukin,IL)-4、IL-6表达情况。结果:共90例老年性特应性皮炎患者纳入本研究,EASI、PNRS、DLQI评分在治疗期间均呈下降趋势,具体表现为在启动治疗后的前4周内快速下降,随后下降逐渐趋于平缓。两两时间点比较结果表明,治疗后第4周EASI、PNRS和DLQI评分均较治疗前明显降低(P<0.001);治疗后第16周时,以上疗效指标评分均进一步降低,与第4周相比差异有统计学意义(P<0.01),其中EASI评分在各个时间点均比前一时间点明显降低,表明患者皮损持续明显改善。对度普利尤单抗的总体疗效进行评价,治疗4周时有62.89%的患者达到EASI-50(即EASI评分下降≥50%),74.4%的患者DLQI评分下降≥4分;16周时有57.8%的患者达到EASI-75,32.2%的患者达到EASI-90,且所有患者的PNRS、DLQI评分均下降≥4分。外周血炎症指标表达水平检测结果表明,治疗16周后IL-4、IL-6表达水平分别为(31.62±6.23)ng/L、(14.36±2.25)ng/L,均较治疗前明显降低(P<0.001),而IFN-γ的表达水平为(15.37±3.14)ng/L,较治疗前上升(P<0.001)。不良反应主要为结膜炎(2例)、注射部位反应(3例)及背部多发性细菌性毛囊炎(2例),对症治疗均可缓解,未出现严重不良反应。结论:度普利尤单抗在老年AD治疗中表现出良好的疗效,可有效改善瘙痒、皮损等临床症状,并能提高患者生活质量,治疗期间未出现严重的不良反应,安全性较好,值得临床推广。展开更多
目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ra...目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ras homolog gene family member A,RhoA)/Rho关联含卷曲螺旋结合蛋白激酶1(recombinant Rho associated coiled coil containing protein kinase 1,ROCK1)信号通路中的调控机制。方法1-氯-2,4-二硝基苯(1-Chloro-2,4-dinitrobenzene,DNCB)诱导BALB/c小鼠作为AD的模型,测量小鼠的皮肤厚度、脾和淋巴结的重量。甲苯胺蓝和HE染色检测小鼠的背部皮肤和耳朵的病理改变;ELISA检测炎症因子水平;肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)刺激HaCaT细胞建立AD体外模型;采用流式细胞术检测细胞活性氧(reactive oxygen species,ROS);免疫荧光法检测线粒体活性氧(mitochondrion reactive oxygen species,mtROS);TUNEL检测细胞凋亡情况;免疫蛋白印迹法检测HMGB1、RAGE、RhoA、ROCK1蛋白表达情况。结果在体内实验中毛兰素抑制皮肤厚度的增加,减轻脾和淋巴结重量,改善炎症细胞的浸润和肥大细胞脱颗粒,降低炎症因子水平(P<0.05)。在体外实验中,毛兰素减少TNF-α诱导的HaCaT细胞ROS、mtROS的产生(P<0.01)。毛兰素治疗后HMGB1、RAGE、RhoA及ROCK1的蛋白表达量下降(P<0.01);使用RAGE特异性阻断剂(TFA)处理r-HMGB1刺激的HaCaT细胞后,HMGB1的表达没有发生变化,RAGE、RhoA及ROCK1表达减少(P<0.01);在Rho激酶抑制剂Y-27632+r-HMGB1组中,除RAGE的表达没有降低,其余结果与TFA+r-HMGB1组相近。结论毛兰素可能通过调节HMGB1/RAGE-RhoA/ROCK1信号通路缓解特应性皮炎。展开更多
文摘Objective:This study aimed to investigate the association of atopic dermatitis(AD)and anxiety/depression behaviors induced by AD with the intestinal microbiota.Additionally,it sought to evaluate the therapeutic potential of mannan oligosaccharide(MOS)in alleviating AD symptoms through the modulation of the gut microbiota and the enhancement of short-chain fatty acids(SCFAs)production.Methods:Female Kunming mice were challenged with 2,4-dinitrofluorobenzene(DNFB)to induce AD-like symptoms.MOS was administered orally daily for 14 days.On the 6th and 11th days post-modeling,the number of scratching bouts in mice was recorded.Following dissection,epidermal thickness,mast cell infiltration,and serum levels of inflammatory cytokines were measured.Meanwhile,cerebral levels of neurotransmitters,including 5-hydroxytryptamine(5-HT)and norepinephrine(NE),were assessed.The abundance of intestinal microbiota and fecal concentrations of SCFAs were also analyzed.Results:MOS significantly reduced AD-like symptoms by reducing inflammatory cytokines,as reflected in a significant decrease in the number of scratching bouts,epidermal thickness,mast cells and inflammatory cytokine levels.MOS intervention up-regulated the expression of 5-HT and NE,and consequently alleviated anxiety and depression-like behaviors.Furthermore,compared with the AD group,MOS intervention increased the gut microbiota abundance of mice,especially beneficial bacteria such as Bifidobacterium,Lactobacillus and Klebsiella.At the same time,these beneficial bacteria significantly increased the fecal contents of SCFAs,especially propionic acid.Correlation analysis indicated that AD amelioration was positively correlated with fecal SCFAs levels and the proliferation of certain intestinal microbes.Conclusion:MOS intervention could offer a novel approach to managing AD and its psychological comorbidities.
文摘Objective:To investigate the influence of xylooligosaccharides on skin inflammation,behavioral characteristics,neurotransmitters,and gut flora in a mouse model of atopic dermatitis(AD)induced by 2,4-dinitrofluorobenzene(DNFB).Methods:The AD mouse model was created by administration of DNFB for 14 consecutive days.The scoring atopic dermatitis index,enzyme-linked immunosorbent assay(ELISA),histopathology,and immunohistochemical analyses were used to assess inflammation and depression-like behaviors.Furthermore,high-throughput 16S rRNA gene sequencing was used to determine the composition of fecal microbiota.Results:Xylooligosaccharides treatment reduced the number of scratches and skin thickness,mast cell infiltration and the levels of immunoglobulin(Ig)E and T-helper cytokines compared with the AD model group.Meanwhile,xylooligosaccharides treatment reduced the immobility time of mice in the forced swimming test and increased the total movement distance and movement distance in the center area in the open-field test.Furthermore,5-hydroxytryptamine and dopamine expression in the brain was increased following xylooligosaccharides treatment.Using network pharmacology,Gene Ontology analysis showed that the targets were mainly enriched in phosphatase binding and the regulation of leukocyte differentiation,which ameliorated AD mainly through the hypoxia inducible factor-1 and phosphatidylinositide 3-kinase-protein kinase B pathways.16S rRNA gene sequencing,diversity indices,and gut microbial taxonomic composition analysis showed DNFB-induced changes in intestinal microbiota diversity in AD mice.Comparative analysis indicated that xylooligosaccharides intake improved the gut microbiome by dramatically enhancing the concentration of Lactobacillus while decreasing the concentration of Bacteroides in mice.Conclusion:Xylooligosaccharides reduce inflammatory dermatosis and related depression-like behaviors via regulating intestinal homeostasis,having medicinal value as a nutritional and functional ingredient.
文摘Aim The present study aimed to investigate anti-inflammatory activity of 6-AP on murine model of aller- gic contact dermatitis （ACD）. Methods 6＇-acetylpaeoniflorin （6-AP） was synthesized from paeoniflorin （Pae） via acetylation and the structure was characterized by 1H-NMR, 13C-NMR and EI-MS. ACD model was established by repeated application of dinitrochlorobenzene （DNCB） to induce skin immune inflammation. The mice were oral- ly administered 6-AP （35, 70, 140 mg. kg-1 ·d^-l）, Pae （70 rag. kg-1·d^-1） and prednisone （Pre, 5 rag. kg^- 1· d^-1 ） from day 1 to day 7 after Cutaneous inflammation was evaluated by ear swelling and histological exami- nation. Splenocyte proliferation was assayed by the 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyl-2H tetrazolium bromide assay. The cytokine production in the splenocytes was measured by enzyme-linked immunosorbent assay. Results Topical application of DNCB to the skin provoked obvious swelling and inflammatory cell infiltration. 6- AP significantly inhibited ear swelling, decreased inflammatory cell infiltration and epidermal keratinization. Ad- dtionally, 6-AP obviously alleviated the hyperplasia of red pulp and germinal center （GC） appearance, decreased spleen index, decreased spleen index, and inhibited splenocyte proliferation in ACD model, compared to that of Pae. Further, the study indicated that 6-AP treatment could increase IL-10 level, while reduce IL-17 level in splenocytes simultaneously. The correlation analysis displayed significantly positive correlations between IL-17 level and the severity of skin inflammation, while negative correlations between IL-10 level and skin inflammation. Con- clusion 6-AP has a significantly higher anti-inflammatory effect than Pae, and it may be a useful treatment for ACD.
文摘目的探究凉血清肺汤联合硝黄搽剂湿敷治疗面部脂溢性皮炎肺胃热盛证的临床效果。方法回顾性选取2022年1月—2023年1月期间收治的面部脂溢性皮炎肺胃热盛证患者102例,根据随机数字表法分为研究组(51例),常规组(51例)。常规组进行硝黄搽剂湿敷治疗,研究组采用凉血清肺汤联合硝黄搽剂湿敷治疗。比较治疗结束后患者临床疗效,比较治疗结束后患者湿疹面积及严重程度指数(eczema area severity index,EASI)、整体评分(investigator′s global assessment,IGA)、基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)、白细胞介素-1β(interleukin-1β,IL-1β)水平,并比较治疗期间的不良反应情况。结果治疗后,两组患者中医症状评分较治疗前均降低(P<0.05),且研究组低于常规组(P<0.05),研究组、常规组治疗总有效率分别为94.12%(48/51)、72.55%(37/51),研究组较常规组高(P<0.05),治疗后两组IGA、EASI评分降低,研究组较常规组低(P<0.05),两组面部脂溢性皮炎肺胃热盛证患者治疗后MMP-3、IL-1β水平降低,研究组MMP-3、IL-1β水平较常规组低(P<0.05),两组患者不良反应率比较,差异均无统计学意义(P>0.05)。结论凉血清肺汤联合硝黄搽剂湿敷能够提高面部脂溢性皮炎肺胃热盛证患者的临床疗效,缓解症状,降低IGA、EASI评分,改善血清炎症水平,安全性较高。
文摘目的:观察度普利尤单抗治疗老年特应性皮炎(atopic dermatitis,AD)的疗效及安全性。方法:回顾性收集北京安贞医院皮肤性病科2021年1月至2023年10月收治的接受度普利尤单抗治疗至少16周的老年AD患者,比较治疗前、治疗期间以及治疗后的临床指标,包括瘙痒数字评价量表(pruritus numerical rating score,PNRS)、湿疹面积和严重程度指数(eczema area and severity index,EASI)、皮肤病生活质量指数(dermatology life quality index,DLQI),同时记录发生的不良反应;比较治疗前及治疗16周后外周血干扰素γ(interferon-γ,IFN-γ)、白细胞介素(interleukin,IL)-4、IL-6表达情况。结果:共90例老年性特应性皮炎患者纳入本研究,EASI、PNRS、DLQI评分在治疗期间均呈下降趋势,具体表现为在启动治疗后的前4周内快速下降,随后下降逐渐趋于平缓。两两时间点比较结果表明,治疗后第4周EASI、PNRS和DLQI评分均较治疗前明显降低(P<0.001);治疗后第16周时,以上疗效指标评分均进一步降低,与第4周相比差异有统计学意义(P<0.01),其中EASI评分在各个时间点均比前一时间点明显降低,表明患者皮损持续明显改善。对度普利尤单抗的总体疗效进行评价,治疗4周时有62.89%的患者达到EASI-50(即EASI评分下降≥50%),74.4%的患者DLQI评分下降≥4分;16周时有57.8%的患者达到EASI-75,32.2%的患者达到EASI-90,且所有患者的PNRS、DLQI评分均下降≥4分。外周血炎症指标表达水平检测结果表明,治疗16周后IL-4、IL-6表达水平分别为(31.62±6.23)ng/L、(14.36±2.25)ng/L,均较治疗前明显降低(P<0.001),而IFN-γ的表达水平为(15.37±3.14)ng/L,较治疗前上升(P<0.001)。不良反应主要为结膜炎(2例)、注射部位反应(3例)及背部多发性细菌性毛囊炎(2例),对症治疗均可缓解,未出现严重不良反应。结论:度普利尤单抗在老年AD治疗中表现出良好的疗效,可有效改善瘙痒、皮损等临床症状,并能提高患者生活质量,治疗期间未出现严重的不良反应,安全性较好,值得临床推广。
文摘目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ras homolog gene family member A,RhoA)/Rho关联含卷曲螺旋结合蛋白激酶1(recombinant Rho associated coiled coil containing protein kinase 1,ROCK1)信号通路中的调控机制。方法1-氯-2,4-二硝基苯(1-Chloro-2,4-dinitrobenzene,DNCB)诱导BALB/c小鼠作为AD的模型,测量小鼠的皮肤厚度、脾和淋巴结的重量。甲苯胺蓝和HE染色检测小鼠的背部皮肤和耳朵的病理改变;ELISA检测炎症因子水平;肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)刺激HaCaT细胞建立AD体外模型;采用流式细胞术检测细胞活性氧(reactive oxygen species,ROS);免疫荧光法检测线粒体活性氧(mitochondrion reactive oxygen species,mtROS);TUNEL检测细胞凋亡情况;免疫蛋白印迹法检测HMGB1、RAGE、RhoA、ROCK1蛋白表达情况。结果在体内实验中毛兰素抑制皮肤厚度的增加,减轻脾和淋巴结重量,改善炎症细胞的浸润和肥大细胞脱颗粒,降低炎症因子水平(P<0.05)。在体外实验中,毛兰素减少TNF-α诱导的HaCaT细胞ROS、mtROS的产生(P<0.01)。毛兰素治疗后HMGB1、RAGE、RhoA及ROCK1的蛋白表达量下降(P<0.01);使用RAGE特异性阻断剂(TFA)处理r-HMGB1刺激的HaCaT细胞后,HMGB1的表达没有发生变化,RAGE、RhoA及ROCK1表达减少(P<0.01);在Rho激酶抑制剂Y-27632+r-HMGB1组中,除RAGE的表达没有降低,其余结果与TFA+r-HMGB1组相近。结论毛兰素可能通过调节HMGB1/RAGE-RhoA/ROCK1信号通路缓解特应性皮炎。
