Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,establis...Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,established DKD group,and advanced DKD group.All patients were classified according to traditional Chinese medicine(TCM)syndrome type,and clinical indexes were collected for statistical analysis.Results:A total of 183 DKD patients were included in this study.Fibroblast growth factor 23(FGF23),chitinase-3-like protein 1(CHI3L1),endocan,tumor necrosis factor receptor 1(TNFR1),secretory leukocyte protease inhibitor(SLPI),and vascular endothelial growth factor A(VEGF-A)were increased in advanced DKD.FGF23,CHI3L1,endocan,SLPI,and TNFR1 showed a negative correlation with estimated glomerular filtration rate(eGFR),while they had a positive correlation with 24 h urine protein.After adjusting for age,gender,diabetes duration,body mass index(BMI),hemoglobin,glucose,uric acid,24 h urine protein,cholesterol,triglyceride,low-density lipoprotein,and hemoglobin A1c(HbA1c),the multiple regression analysis showed that FGF23,endocan,TNFR1,and SLPI significantly correlated with eGFR.Conclusions:FGF23,endocan,TNFR1,and SLPI are elevated in advanced DKD compared with early stage,and they may take part in the pathogenesis and progression of DKD.Our study provides useful biomarkers for predicting the appearance of damp-heat syndrome,including FGF23,endocan,TNFR1,and SLPI.展开更多
One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on th...One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8+CD28- Treg cells and found that the MSCs could not only increase the proportion of CD8+CD28- T cells, but also enhance CD8+CD28-T cells' ability of hampering naive CD4+ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4+ T cells and inducing the apoptosis of activated CD4+ T cells. Mechanistically, the MSCs affected the functions of the CD8+CD28- T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8+CD28+ T cells to CD8+CD28- T cells, but did increase the proportion of CD8+CD28- T cells by reducing their rate of apoptosis. In summary, this study shows that MSCs can enhance the regulatory function of CD8+CD28- Treg cells, shedding new light on MSCs-mediated immune regulation.展开更多
Mesenchymal stromal cells(MSCs)have been considered a promising alternative for treatment of acute respiratory distress syndrome(ARDS).However,there is significant heterogeneity in their therapeutic efficacy,largely o...Mesenchymal stromal cells(MSCs)have been considered a promising alternative for treatment of acute respiratory distress syndrome(ARDS).However,there is significant heterogeneity in their therapeutic efficacy,largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs.Here,we hypothesize that the cholinergic antiinflammatory pathway(CAP),which is recognized as a neuroimmunological pathway,may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS.Using lipopolysaccharide(LPS)and bacterial lung inflammation models,we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase(ChAT)and vesicular acetylcholine transporter(VAChT)in lung tissue were significantly increased 6 hours after MSC infusion.When the vagus nerve was blocked orα7 nicotinic acetylcholine(ACh)receptor(α7nAChR)-knockout mice were used,the therapeutic effects of MSCs were significantly reduced,suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment.Our results further showed that MSC-derived prostaglandin E2(PGE2)likely promoted ACh synthesis and release.Additionally,based on the efficacy of nAChR andα7nAChR agonists,we found that lobeline,the nicotinic cholinergic receptor excitation stimulant,may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study(ChiCTR2100047403).In summary,we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome,providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.展开更多
基金This project was supported by the Fundamental Research Funds for the Central Universities(2017-JYB-JS-075)National Key Project for Drug Discovery(2017ZX09304019).
文摘Objective:To explore the role of endothelial biomarkers in predicting damp-heat syndrome in diabetic kidney disease(DKD).Methods:A total of 183 patients with DKD were divided into 3 groups:the early DKD group,established DKD group,and advanced DKD group.All patients were classified according to traditional Chinese medicine(TCM)syndrome type,and clinical indexes were collected for statistical analysis.Results:A total of 183 DKD patients were included in this study.Fibroblast growth factor 23(FGF23),chitinase-3-like protein 1(CHI3L1),endocan,tumor necrosis factor receptor 1(TNFR1),secretory leukocyte protease inhibitor(SLPI),and vascular endothelial growth factor A(VEGF-A)were increased in advanced DKD.FGF23,CHI3L1,endocan,SLPI,and TNFR1 showed a negative correlation with estimated glomerular filtration rate(eGFR),while they had a positive correlation with 24 h urine protein.After adjusting for age,gender,diabetes duration,body mass index(BMI),hemoglobin,glucose,uric acid,24 h urine protein,cholesterol,triglyceride,low-density lipoprotein,and hemoglobin A1c(HbA1c),the multiple regression analysis showed that FGF23,endocan,TNFR1,and SLPI significantly correlated with eGFR.Conclusions:FGF23,endocan,TNFR1,and SLPI are elevated in advanced DKD compared with early stage,and they may take part in the pathogenesis and progression of DKD.Our study provides useful biomarkers for predicting the appearance of damp-heat syndrome,including FGF23,endocan,TNFR1,and SLPI.
基金This study was supported by the National Basic Research Program of China (2012CBA01302, 2010CB945400), the National Natural Science Foundation of China (31171398, 81271265, 81425016), the Key Scientific and Technological Projects of Guangdong Province (2007A032100003), the Natural Science Foundation of Guangdong Province ( S2013030013305 ), the Key Scientific and Technological Program of Guangzhou City (201400000003-3, 201300000089, 2010U1-E00551 ) and Guangdong Department of Science & Technology Translational Medicine Center grant (2011A080300002).
文摘One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8+CD28- Treg cells and found that the MSCs could not only increase the proportion of CD8+CD28- T cells, but also enhance CD8+CD28-T cells' ability of hampering naive CD4+ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4+ T cells and inducing the apoptosis of activated CD4+ T cells. Mechanistically, the MSCs affected the functions of the CD8+CD28- T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8+CD28+ T cells to CD8+CD28- T cells, but did increase the proportion of CD8+CD28- T cells by reducing their rate of apoptosis. In summary, this study shows that MSCs can enhance the regulatory function of CD8+CD28- Treg cells, shedding new light on MSCs-mediated immune regulation.
基金supported by the National Key Research and Development Program of China,Stem Cell and Translational Research(2018YFA0107200,2019YFA0110303,2021YFA1100600)National Natural Science Foundation of China(81730005,32130046,81900075,81970109,82170540,81721003)+2 种基金Natural Science Foundation of Guangdong Province(2018A0303130305,2021A1515011759,2022A1515012452,2022A1515011919)Key Research and Development Program of Guangdong Province(2019B020236002)Key Scientific and Technological Program of Guangzhou City(201803040011),and Pearl River S&T Nova Program of Guangzhou(201906010095).
文摘Mesenchymal stromal cells(MSCs)have been considered a promising alternative for treatment of acute respiratory distress syndrome(ARDS).However,there is significant heterogeneity in their therapeutic efficacy,largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs.Here,we hypothesize that the cholinergic antiinflammatory pathway(CAP),which is recognized as a neuroimmunological pathway,may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS.Using lipopolysaccharide(LPS)and bacterial lung inflammation models,we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase(ChAT)and vesicular acetylcholine transporter(VAChT)in lung tissue were significantly increased 6 hours after MSC infusion.When the vagus nerve was blocked orα7 nicotinic acetylcholine(ACh)receptor(α7nAChR)-knockout mice were used,the therapeutic effects of MSCs were significantly reduced,suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment.Our results further showed that MSC-derived prostaglandin E2(PGE2)likely promoted ACh synthesis and release.Additionally,based on the efficacy of nAChR andα7nAChR agonists,we found that lobeline,the nicotinic cholinergic receptor excitation stimulant,may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study(ChiCTR2100047403).In summary,we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome,providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.