Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a signifi...Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge.Inspired by metalloenzymes with well-defined coordination structures,a series of MOFs containing halogen-coordinated copper nodes(Cu-X MOFs,X=Cl,Br,I)are employed to elucidate their structure–activity relationship.Intriguingly,experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center.The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes.More importantly,by performing enzyme-mimicking catalysis,the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress,thus effectively relieving ocular chemical burns.Mechanistically,the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways.Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and,more significantly,demonstrating their potential therapeutic effect in ophthalmic disease.展开更多
Corneal blindness caused by limbal stem cell deficiency(LSCD) is one of the most common debilitating eye disorders. Thus far, the most effective treatment for LSCD is corneal transplantation, which is often hindered b...Corneal blindness caused by limbal stem cell deficiency(LSCD) is one of the most common debilitating eye disorders. Thus far, the most effective treatment for LSCD is corneal transplantation, which is often hindered by the shortage of donors. Pluripotent stem cell technology including embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs) have opened new avenues for treating this disease. iPSCs-derived corneal epithelial cells provide an autologous and unlimited source of cells for the treatment of LSCD. On the other hand, iPSCs of LSCD patients can be used for iPSCs-corneal disease model and new drug discovery. However, prior to clinical trial, the efficacy and safety of these cells in patients with LSCD should be proved. Here we focused on the current status of iPSCs-derived corneal epithelial cells used for cell therapy as well as for corneal disease modeling. The challenges and potential of iPSCs-derived corneal epithelial cells as a choice for clinical treatment in corneal disease were also discussed.展开更多
目的探索异甘草酸镁治疗自身免疫样药物性肝损伤的临床疗效和安全性。方法选取首都医科大学附属北京佑安医院2016年7月-2019年1月住院的自身免疫样药物性肝损伤患者53例为观察组,另选不伴有自身免疫现象的药物性肝损伤患者50例为对照组...目的探索异甘草酸镁治疗自身免疫样药物性肝损伤的临床疗效和安全性。方法选取首都医科大学附属北京佑安医院2016年7月-2019年1月住院的自身免疫样药物性肝损伤患者53例为观察组,另选不伴有自身免疫现象的药物性肝损伤患者50例为对照组。所有患者给予异甘草酸镁200 mg/d,治疗4周。观察治疗前后患者肝功能情况,观察治疗前后观察组患者的免疫学指标,记录两组患者的不良反应。治疗结束后每月随访肝功能,随访时间6个月。正态分布计量资料组间比较采用t检验,非正态分布的计量资料采用Mann-Whitney U检验,计数资料组间比较采用χ^2检验或Fisher精确概率检验。结果观察组治疗后与治疗前比较,ALT[35.4(29.2~42.0)U/L vs 289.0(226.6~460.3)U/L,Z=-8.661,P<0.001]、AST[46.3(15.6~183.5)U/L vs 306.3(32.2~589.8)U/L,Z=-5.271,P<0.001]、GGT[77.0(53.2~183.2)U/L vs 129.0(77.8~232.5)U/L,Z=-3.437,P=0.001)]、ALP[83.1(64.9~83.1U/L vs 119.4(104.9~146.9)U/L,Z=-3.485,P<0.001]和TBil[(27.5±10.3)μmol/L vs(59.7±18.6)μmol/L,t=6.673,P<0.001]水平均明显降低;对照组患者治疗后与治疗前比较,ALT[33.1(14.9~106.4)U/L vs 300.6(206.8~679.5)U/L,Z=-8.232,P<0.001]、AST[44.1(20.8~151.6)U/L vs 321.7(36.2~553.2)U/L,Z=-3.549,P<0.001]、GGT[82.7(50.6~168.5)U/L vs 133.5(72.2~254.2)U/L,Z=-2.364,P=0.018]、ALP[87.6(74.3~139.4)U/L vs 128.0(106.3~201.4)U/L,Z=-4.303,P<0.001]和TBil[(23.8±10.9)μmol/L vs(58.3±19.8)μmol/L,t=-8.450,P<0.001]水平也明显降低。但治疗后两组间比较差异均无统计学意义(P值均>0.05)。治疗后观察组患者IgG水平由(15.8±3.2)g/L降至(14.2±2.0)g/L,治疗前IgG水平升高(>16 g/L)患者22例中18例(81.8%)恢复正常。36例ANA阳性患者19例(52.7%)阴转。两组患者均无严重不良反应。行肝穿病理检查患者中,观察组患者中性粒细胞和(或)嗜酸性粒细胞浸润(17/32,53.1%)明显高于对照组(3/17,17.5%)(χ^2=5.785,P=0.016)。结论异甘草酸镁用于治疗自身免疫样药物性肝损伤安全有效,是临床治疗的可选择方案。展开更多
基金the National Key R&D Program of China(Grant No.2020YFA0908100)the National Nature Science Foundation(Grant Nos.12274356,82070931,and 82271045)+1 种基金Fundamental Research Funds for the Central Universities(20720220022)the 111 Project(B16029)。
文摘Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge.Inspired by metalloenzymes with well-defined coordination structures,a series of MOFs containing halogen-coordinated copper nodes(Cu-X MOFs,X=Cl,Br,I)are employed to elucidate their structure–activity relationship.Intriguingly,experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center.The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes.More importantly,by performing enzyme-mimicking catalysis,the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress,thus effectively relieving ocular chemical burns.Mechanistically,the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways.Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and,more significantly,demonstrating their potential therapeutic effect in ophthalmic disease.
文摘Corneal blindness caused by limbal stem cell deficiency(LSCD) is one of the most common debilitating eye disorders. Thus far, the most effective treatment for LSCD is corneal transplantation, which is often hindered by the shortage of donors. Pluripotent stem cell technology including embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs) have opened new avenues for treating this disease. iPSCs-derived corneal epithelial cells provide an autologous and unlimited source of cells for the treatment of LSCD. On the other hand, iPSCs of LSCD patients can be used for iPSCs-corneal disease model and new drug discovery. However, prior to clinical trial, the efficacy and safety of these cells in patients with LSCD should be proved. Here we focused on the current status of iPSCs-derived corneal epithelial cells used for cell therapy as well as for corneal disease modeling. The challenges and potential of iPSCs-derived corneal epithelial cells as a choice for clinical treatment in corneal disease were also discussed.
文摘目的探索异甘草酸镁治疗自身免疫样药物性肝损伤的临床疗效和安全性。方法选取首都医科大学附属北京佑安医院2016年7月-2019年1月住院的自身免疫样药物性肝损伤患者53例为观察组,另选不伴有自身免疫现象的药物性肝损伤患者50例为对照组。所有患者给予异甘草酸镁200 mg/d,治疗4周。观察治疗前后患者肝功能情况,观察治疗前后观察组患者的免疫学指标,记录两组患者的不良反应。治疗结束后每月随访肝功能,随访时间6个月。正态分布计量资料组间比较采用t检验,非正态分布的计量资料采用Mann-Whitney U检验,计数资料组间比较采用χ^2检验或Fisher精确概率检验。结果观察组治疗后与治疗前比较,ALT[35.4(29.2~42.0)U/L vs 289.0(226.6~460.3)U/L,Z=-8.661,P<0.001]、AST[46.3(15.6~183.5)U/L vs 306.3(32.2~589.8)U/L,Z=-5.271,P<0.001]、GGT[77.0(53.2~183.2)U/L vs 129.0(77.8~232.5)U/L,Z=-3.437,P=0.001)]、ALP[83.1(64.9~83.1U/L vs 119.4(104.9~146.9)U/L,Z=-3.485,P<0.001]和TBil[(27.5±10.3)μmol/L vs(59.7±18.6)μmol/L,t=6.673,P<0.001]水平均明显降低;对照组患者治疗后与治疗前比较,ALT[33.1(14.9~106.4)U/L vs 300.6(206.8~679.5)U/L,Z=-8.232,P<0.001]、AST[44.1(20.8~151.6)U/L vs 321.7(36.2~553.2)U/L,Z=-3.549,P<0.001]、GGT[82.7(50.6~168.5)U/L vs 133.5(72.2~254.2)U/L,Z=-2.364,P=0.018]、ALP[87.6(74.3~139.4)U/L vs 128.0(106.3~201.4)U/L,Z=-4.303,P<0.001]和TBil[(23.8±10.9)μmol/L vs(58.3±19.8)μmol/L,t=-8.450,P<0.001]水平也明显降低。但治疗后两组间比较差异均无统计学意义(P值均>0.05)。治疗后观察组患者IgG水平由(15.8±3.2)g/L降至(14.2±2.0)g/L,治疗前IgG水平升高(>16 g/L)患者22例中18例(81.8%)恢复正常。36例ANA阳性患者19例(52.7%)阴转。两组患者均无严重不良反应。行肝穿病理检查患者中,观察组患者中性粒细胞和(或)嗜酸性粒细胞浸润(17/32,53.1%)明显高于对照组(3/17,17.5%)(χ^2=5.785,P=0.016)。结论异甘草酸镁用于治疗自身免疫样药物性肝损伤安全有效,是临床治疗的可选择方案。
