Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and l...Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and lupus nephritis(LN).Methods Totally,91 participants were enrolled between February 2023 and January 2024 including 58 SLE patients[30 with nonrenal-SLE and 28 with Lupus nephritis(LN)]and 33 healthy controls(HC).Ultracentrifugation was used to isolate serum exosomes,which were analyzed for their metabolic profiles using liquid chromatography–tandem mass spectrometry(LC–MS/MS).Endogenous metabolites were identified via public metabolite databases.Random Forest,Lasso regression and Support Vector Machine Recursive Feature Elimination(SVM-RFE)algorithms were employed to screen key metabolites,and a prediction model was constructed for SLE diagnosis and LN discrimination.ROC curves were constructed to determine the potential of these differential exosome-derived metabolites for the diagnosis of SLE.Furthermore,Spearman’s correlation was employed to evaluate the potential links between exosome-derived metabolites and the clinical parameters which reflect disease progression.Results A total of 586 endogenous serum exosome-derived metabolites showed differential expression,with 225 exosome-derived metabolites significantly upregulated,88 downregulated and 273 exhibiting no notable changes in the HC and SLE groups.Machine learning algorithms revealed three differential metabolites:Pro-Asn-Gln-Met-Ser,C24:1 sphingolipid,and protoporphyrin IX,which exhibited AUC values of 0.998,0.992 and 0.969 respectively,for distinguishing between the SLE and HC groups,with a combined AUC of 1.0.In distinguishing between the LN and SLE groups,the AUC values for these metabolites were 0.920,0.893 and 0.865,respectively,with a combined AUC of 0.931,demonstrating excellent diagnostic performance.Spearman correlation analysis revealed that Pro-Asn-Gln-Met-Ser and protoporphyrin IX were positively correlated with the SLE Disease Activity Index(SLEDAI)scores,urinary protein/creatinine ratio(ACR)and urinary protein levels,while C24:1 sphingolipid exhibited a negative correlation.Conclusions This study provides the first comprehensive characterization of the exosome-derived metabolites in SLE and established a promising prediction model for SLE and LN discrimination.The correlation between exosome-derived metabolites and key clinical parameters strongly indicated their potential role in SLE pathological progression.展开更多
Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac re...Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac repair efficiency post-MI, culminating in adverse ventricular remodeling and potential heart failure. To address the diverse pathological stages of MI, an injectable composite hydrogel containing versatile nanoparticles was developed. In this study, mesoporous silicon nanoparticles (MSNs) served as carriers for encapsulating microRNA-29b (miR-29b) mimics with antifibrotic activity, subsequently coated with a complex of natural antioxidant tannic acid and zinc ions (TA/Zn). These nanoparticles were then embedded into a biocompatible alginate hydrogel to enhance retention within the infarcted myocardium. Upon injection into the infarcted region of MI mice, the composite hydrogel gradually released the nanoparticles as it degraded. Initially, the TA/Zn complex on the outer layer scavenged reactive oxygen species, thereby inhibiting cell apoptosis. The subsequent dissociation of the TA/Zn complex led to the release of the encapsulated miR-29b mimics that could inhibit the activation of cardiac fibroblasts and collagen production, thereby alleviating fibrosis progression. Overall, this composite hydrogel demonstrated the potential to reduce infarct size and improve cardiac function, suggesting its promise as a synergistic therapeutic approach for repairing infarcted myocardium.展开更多
基金funded by National Natural Science Foundation of China to Ping Yang with Grant number No.82202600by Nanjing Drum Tower Hospital to Ping Yang with Grant number No.2024-LCYJ-MS-11then to Shou-bin Zhan with Grant number No.2023-JCYJ-QP-25.
文摘Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and lupus nephritis(LN).Methods Totally,91 participants were enrolled between February 2023 and January 2024 including 58 SLE patients[30 with nonrenal-SLE and 28 with Lupus nephritis(LN)]and 33 healthy controls(HC).Ultracentrifugation was used to isolate serum exosomes,which were analyzed for their metabolic profiles using liquid chromatography–tandem mass spectrometry(LC–MS/MS).Endogenous metabolites were identified via public metabolite databases.Random Forest,Lasso regression and Support Vector Machine Recursive Feature Elimination(SVM-RFE)algorithms were employed to screen key metabolites,and a prediction model was constructed for SLE diagnosis and LN discrimination.ROC curves were constructed to determine the potential of these differential exosome-derived metabolites for the diagnosis of SLE.Furthermore,Spearman’s correlation was employed to evaluate the potential links between exosome-derived metabolites and the clinical parameters which reflect disease progression.Results A total of 586 endogenous serum exosome-derived metabolites showed differential expression,with 225 exosome-derived metabolites significantly upregulated,88 downregulated and 273 exhibiting no notable changes in the HC and SLE groups.Machine learning algorithms revealed three differential metabolites:Pro-Asn-Gln-Met-Ser,C24:1 sphingolipid,and protoporphyrin IX,which exhibited AUC values of 0.998,0.992 and 0.969 respectively,for distinguishing between the SLE and HC groups,with a combined AUC of 1.0.In distinguishing between the LN and SLE groups,the AUC values for these metabolites were 0.920,0.893 and 0.865,respectively,with a combined AUC of 0.931,demonstrating excellent diagnostic performance.Spearman correlation analysis revealed that Pro-Asn-Gln-Met-Ser and protoporphyrin IX were positively correlated with the SLE Disease Activity Index(SLEDAI)scores,urinary protein/creatinine ratio(ACR)and urinary protein levels,while C24:1 sphingolipid exhibited a negative correlation.Conclusions This study provides the first comprehensive characterization of the exosome-derived metabolites in SLE and established a promising prediction model for SLE and LN discrimination.The correlation between exosome-derived metabolites and key clinical parameters strongly indicated their potential role in SLE pathological progression.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20231314)the National Natural Science Foundation of China(No.92168203)+4 种基金the National Key R&D Program of China(No.2022YFA1104300)the Jiangsu Cardiovascular Medicine Innovation Center(No.CXZX202210)the Suzhou“Science and Education Revitalize Health”Youth Science and Technology Project(No.KJXW2021001)the Suzhou“Science and Education Revitalize Health”Youth Science and Technology Project(No.KJXW2021001)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac repair efficiency post-MI, culminating in adverse ventricular remodeling and potential heart failure. To address the diverse pathological stages of MI, an injectable composite hydrogel containing versatile nanoparticles was developed. In this study, mesoporous silicon nanoparticles (MSNs) served as carriers for encapsulating microRNA-29b (miR-29b) mimics with antifibrotic activity, subsequently coated with a complex of natural antioxidant tannic acid and zinc ions (TA/Zn). These nanoparticles were then embedded into a biocompatible alginate hydrogel to enhance retention within the infarcted myocardium. Upon injection into the infarcted region of MI mice, the composite hydrogel gradually released the nanoparticles as it degraded. Initially, the TA/Zn complex on the outer layer scavenged reactive oxygen species, thereby inhibiting cell apoptosis. The subsequent dissociation of the TA/Zn complex led to the release of the encapsulated miR-29b mimics that could inhibit the activation of cardiac fibroblasts and collagen production, thereby alleviating fibrosis progression. Overall, this composite hydrogel demonstrated the potential to reduce infarct size and improve cardiac function, suggesting its promise as a synergistic therapeutic approach for repairing infarcted myocardium.
