Oxidative stress caused by oxalate is one of the key pathogenic factors causing renal tubular injury and kidney stone formation.Recent studies have reported that ellagic acid(a natural polyphenol abundantly present in...Oxidative stress caused by oxalate is one of the key pathogenic factors causing renal tubular injury and kidney stone formation.Recent studies have reported that ellagic acid(a natural polyphenol abundantly present in various fruits,nuts and medicinal plants with known antioxidant properties)has potential renoprotective effects,but with unclear molecular mechanisms.To investigate the cellular impact of ellagic acid,we applied quanti-tative proteomics,bioinformatics(protein interaction network mapping,gene ontology enrichment,and K-means clustering),and functional assays(Western blotting,OxyBlot assay,MitoTracker staining,and protein aggre-gation assay)to identify key pathways and functional clusters mediated by ellagic acid.Proteomic profiling identified 8 downregulated and 13 upregulated proteins induced by ellagic acid.Bioinformatic analyses iden-tified some important central regulatory nodes within interaction networks,including ATIC,HSPH1 and TPI1 among downregulated proteins,and hnRNPK,EIF6 and HSPA8 among upregulated ones.Functional annotation indicated that stress response and mitochondrial function were involved.Functional validation revealed that ellagic acid prevented oxalate-induced protein oxidation and preserved mitochondrial integrity and membrane potential,indicating its strong antioxidant effects.However,ellagic acid did not affect protein aggregation.In conclusion,ellagic acid exerted multifaceted cytoprotective effects in renal tubular cells by modulating the expression of several proteins and their interaction networks,mitigating oxidative protein damage,and pre-serving mitochondrial function.These findings provide mechanistic insights into the renoprotective actions of ellagic acid and support its promise as a therapeutic agent against renal injury caused by oxalate.展开更多
Background:Aspirin has demonstrated safety and efficacy for venous thromboembolism(VTE)prophylaxis following total hip arthroplasty(THA);however,inconsistent dose regimens have been reported in the literature.This stu...Background:Aspirin has demonstrated safety and efficacy for venous thromboembolism(VTE)prophylaxis following total hip arthroplasty(THA);however,inconsistent dose regimens have been reported in the literature.This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.Methods:Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin(100 mg twice daily)or rivaroxaban(10 mg once daily).Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence,deep vein thrombosis(DVT)on Doppler ultrasonography,total blood loss(TBL),laboratory bloodwork,Harris hip score(HHS),post-operative recovery,and the incidence of other complications.Results:We included 70 patients in this study;34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis,respectively.No cases of symptomatic VTE occurred in this study.The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group(8.8%vs.8.3%,χ^(2)=0.01,P=0.91),confirming the non-inferiority of aspirin for DVT prophylaxis(χ^(2)=2.29,P=0.01).The calculated TBL in the aspirin group(944.9 mL[658.5-1137.8 mL])was similar to that in the rivaroxaban group(978.3 mL[747.4-1740.6mL])(χ^(2)=1.55,P=0.12).However,there were no significant inter-group differences in HHS at post-operative day(POD)30(Aspirin:81.0[78.8-83.0],Rivaroxaban:81.0[79.3-83.0],χ^(2)=0.43,P=0.67)and POD 90(Aspirin:90.0[89.0-92.0],Rivaroxaban:91.5[88.3-92.8],χ^(2)=0.77,P=0.44),the incidence of bleeding events(2.9%vs.8.3%,χ^(2)=0.96,P=0.33),or gastrointestinal complications(2.9%vs.5.6%,χ^(2)=1.13,P=0.29).Conclusion:In terms of safety and efficacy,the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA.This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.Trial Registration:Chictr.org,ChiCTR18000202894;http://www.chictr.org.cn/showproj.aspx?proj=33284.展开更多
Sjögren’s disease(SjD)is an autoimmune and inflammatory disease characterized by immune-mediated impairment of salivary and lacrimal gland functions,causing dryness in the mouth and eyes.SjD also involves other ...Sjögren’s disease(SjD)is an autoimmune and inflammatory disease characterized by immune-mediated impairment of salivary and lacrimal gland functions,causing dryness in the mouth and eyes.SjD also involves other exocrine glands in the respiratory and gastrointestinal tracts and the skin and has a wide and variable range of extraglandular and systemic manifestations[1].展开更多
基金supported by the National Research Council of Thailand(NRCT):High-Potential Research Team Grant Program(N42A660625).
文摘Oxidative stress caused by oxalate is one of the key pathogenic factors causing renal tubular injury and kidney stone formation.Recent studies have reported that ellagic acid(a natural polyphenol abundantly present in various fruits,nuts and medicinal plants with known antioxidant properties)has potential renoprotective effects,but with unclear molecular mechanisms.To investigate the cellular impact of ellagic acid,we applied quanti-tative proteomics,bioinformatics(protein interaction network mapping,gene ontology enrichment,and K-means clustering),and functional assays(Western blotting,OxyBlot assay,MitoTracker staining,and protein aggre-gation assay)to identify key pathways and functional clusters mediated by ellagic acid.Proteomic profiling identified 8 downregulated and 13 upregulated proteins induced by ellagic acid.Bioinformatic analyses iden-tified some important central regulatory nodes within interaction networks,including ATIC,HSPH1 and TPI1 among downregulated proteins,and hnRNPK,EIF6 and HSPA8 among upregulated ones.Functional annotation indicated that stress response and mitochondrial function were involved.Functional validation revealed that ellagic acid prevented oxalate-induced protein oxidation and preserved mitochondrial integrity and membrane potential,indicating its strong antioxidant effects.However,ellagic acid did not affect protein aggregation.In conclusion,ellagic acid exerted multifaceted cytoprotective effects in renal tubular cells by modulating the expression of several proteins and their interaction networks,mitigating oxidative protein damage,and pre-serving mitochondrial function.These findings provide mechanistic insights into the renoprotective actions of ellagic acid and support its promise as a therapeutic agent against renal injury caused by oxalate.
基金supported by the National Nature Science Foundation in China(No.81871740).
文摘Background:Aspirin has demonstrated safety and efficacy for venous thromboembolism(VTE)prophylaxis following total hip arthroplasty(THA);however,inconsistent dose regimens have been reported in the literature.This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.Methods:Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin(100 mg twice daily)or rivaroxaban(10 mg once daily).Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence,deep vein thrombosis(DVT)on Doppler ultrasonography,total blood loss(TBL),laboratory bloodwork,Harris hip score(HHS),post-operative recovery,and the incidence of other complications.Results:We included 70 patients in this study;34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis,respectively.No cases of symptomatic VTE occurred in this study.The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group(8.8%vs.8.3%,χ^(2)=0.01,P=0.91),confirming the non-inferiority of aspirin for DVT prophylaxis(χ^(2)=2.29,P=0.01).The calculated TBL in the aspirin group(944.9 mL[658.5-1137.8 mL])was similar to that in the rivaroxaban group(978.3 mL[747.4-1740.6mL])(χ^(2)=1.55,P=0.12).However,there were no significant inter-group differences in HHS at post-operative day(POD)30(Aspirin:81.0[78.8-83.0],Rivaroxaban:81.0[79.3-83.0],χ^(2)=0.43,P=0.67)and POD 90(Aspirin:90.0[89.0-92.0],Rivaroxaban:91.5[88.3-92.8],χ^(2)=0.77,P=0.44),the incidence of bleeding events(2.9%vs.8.3%,χ^(2)=0.96,P=0.33),or gastrointestinal complications(2.9%vs.5.6%,χ^(2)=1.13,P=0.29).Conclusion:In terms of safety and efficacy,the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA.This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.Trial Registration:Chictr.org,ChiCTR18000202894;http://www.chictr.org.cn/showproj.aspx?proj=33284.
基金supported by grants from the U.S.National Institutes of Health(Al163045 to KC)the Spanish Ministry of Science,Innovation and Universities(RTI2018-093894-B-100 to AC).
文摘Sjögren’s disease(SjD)is an autoimmune and inflammatory disease characterized by immune-mediated impairment of salivary and lacrimal gland functions,causing dryness in the mouth and eyes.SjD also involves other exocrine glands in the respiratory and gastrointestinal tracts and the skin and has a wide and variable range of extraglandular and systemic manifestations[1].
