Objective Rheumatoid arthritis(RA)progression is associated with the balance of T-regulatory(Treg)and T-helper 17(Th17)cells,while the role of microRNAs(miRs)in regulating Treg/Th17 cell balance has not been clarified...Objective Rheumatoid arthritis(RA)progression is associated with the balance of T-regulatory(Treg)and T-helper 17(Th17)cells,while the role of microRNAs(miRs)in regulating Treg/Th17 cell balance has not been clarified.This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3(SOCS3)axis in the RA mouse model.Methods A mouse model of collagen-induced arthritis(CIA)was established in male DBA/1J mice.Twenty-two days after CIA induction,the mice received daily treatment with moxibustion for 12 times.Pathological scores were assessed according to the levels of synovial hyperplasia.The expression levels of cytokines interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay.The cluster of differentiation 4(CD4+)splenocytes was analyzed by fluorescence-activated cell sorting.The expression levels of RA-related miRs and target genes were subsequently detected,and the target of miR-221 was confirmed by the dual-luciferase reporter assay.Results It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β,IL-6,TNF-α,IFN-γand IL-17,while upregulated the expression level of IL-10.The Treg/Th17 cell balance was regulated by moxibustion treatment.The expression level of miR-221 was suppressed by moxibustion treatment.Furthermore,SOCS3 was found as the direct target of miR-221,which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.Conclusion Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.展开更多
AIM: To investigate the candidate microRNA(miRNA), miR-221 as a novel biomarker for diabetic retinopathy(DR) in patients associated with type 2 diabetes(T2D).METHODS: The subjects involved were divided into four group...AIM: To investigate the candidate microRNA(miRNA), miR-221 as a novel biomarker for diabetic retinopathy(DR) in patients associated with type 2 diabetes(T2D).METHODS: The subjects involved were divided into four groups: healthy control(HC), no diabetic retinopathy(NDR), non-proliferative diabetic retinopathy(NPDR) and proliferative diabetic retinopathy(PDR) group. Serum miR-221 was validated by real-time quantitative reversetranscription polymerase chain reaction(qRT-PCR). Also, serum angiotensin II(Ang II) and vascular endothelial growth factor(VEGF) were examined by enzyme-linked immunosorbent assay. In addition, receiver operating characteristic(ROC) curve was performed to explore the diagnostic accuracy of miR-221, Ang Ⅱ and VEGF for DR in patients with T2D. Spearman’s rank correlation coefficient was executed to estimate the correlations of serum miR-221 with metabolic parameters and serum markers in patients with T2D.RESULTS: Primarily, serum miR-221, Ang Ⅱ and VEGF were increased significantly in T2D patients compared to HC participant respectively, and progressive up-regulated in NDR, NPDR and PDR groups(P<0.001). Additionally, miR-221 in serum was remarkably positively correlatedwith metabolic parameters such as glycated hemoglobin(r=0.310, P=0.002) and homeostasis model assessment for insulin resistance(r=0.413, P<0.001), as well as serum markers for instance Ang Ⅱ(r=0.667, P<0.001) and VEGF(r=0.499, P<0.001). Furthermore, serum miR-221(AUC, 0.894; 95%CI, 0.833-0.955; P<0.001), Ang Ⅱ(AUC, 0.888; 95%CI, 0.828-0.949; P<0.001) and VEGF(AUC, 0.785; 95%CI, 0.695-0.875; P<0.001) had evidently diagnostic efficiency in DR, and miR-221 is the most effective among them.CONCLUSION: Serum miR-221 as a potential biomarker could be related to not only occurrence but also progression for DR in patients with T2D. However, a prospective clinical trial is warranted.展开更多
基金This study was supported by the National Natural Science Foundation of China(No.81904284)Shanghai Talent Development Fund(No,2020086)Key Discipline Construction Fund of Baoshan Hospital of Integrated Traditional Chinese Medicine and Western Medicine,Shanghai(No.BSYYZDZK-2019-03 and No.BSYYZDZK-2019-04)。
文摘Objective Rheumatoid arthritis(RA)progression is associated with the balance of T-regulatory(Treg)and T-helper 17(Th17)cells,while the role of microRNAs(miRs)in regulating Treg/Th17 cell balance has not been clarified.This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3(SOCS3)axis in the RA mouse model.Methods A mouse model of collagen-induced arthritis(CIA)was established in male DBA/1J mice.Twenty-two days after CIA induction,the mice received daily treatment with moxibustion for 12 times.Pathological scores were assessed according to the levels of synovial hyperplasia.The expression levels of cytokines interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay.The cluster of differentiation 4(CD4+)splenocytes was analyzed by fluorescence-activated cell sorting.The expression levels of RA-related miRs and target genes were subsequently detected,and the target of miR-221 was confirmed by the dual-luciferase reporter assay.Results It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β,IL-6,TNF-α,IFN-γand IL-17,while upregulated the expression level of IL-10.The Treg/Th17 cell balance was regulated by moxibustion treatment.The expression level of miR-221 was suppressed by moxibustion treatment.Furthermore,SOCS3 was found as the direct target of miR-221,which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.Conclusion Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.
基金National Natural Science Foundation of China (No.81371045No.81570866)+3 种基金Science and Technology Program of Liaoning Province,China (No.201002196No.2013225049)Science and Technology Program of Shenyang Municipality,China (No.F13-221-9-37No.18-014-4-41)
文摘AIM: To investigate the candidate microRNA(miRNA), miR-221 as a novel biomarker for diabetic retinopathy(DR) in patients associated with type 2 diabetes(T2D).METHODS: The subjects involved were divided into four groups: healthy control(HC), no diabetic retinopathy(NDR), non-proliferative diabetic retinopathy(NPDR) and proliferative diabetic retinopathy(PDR) group. Serum miR-221 was validated by real-time quantitative reversetranscription polymerase chain reaction(qRT-PCR). Also, serum angiotensin II(Ang II) and vascular endothelial growth factor(VEGF) were examined by enzyme-linked immunosorbent assay. In addition, receiver operating characteristic(ROC) curve was performed to explore the diagnostic accuracy of miR-221, Ang Ⅱ and VEGF for DR in patients with T2D. Spearman’s rank correlation coefficient was executed to estimate the correlations of serum miR-221 with metabolic parameters and serum markers in patients with T2D.RESULTS: Primarily, serum miR-221, Ang Ⅱ and VEGF were increased significantly in T2D patients compared to HC participant respectively, and progressive up-regulated in NDR, NPDR and PDR groups(P<0.001). Additionally, miR-221 in serum was remarkably positively correlatedwith metabolic parameters such as glycated hemoglobin(r=0.310, P=0.002) and homeostasis model assessment for insulin resistance(r=0.413, P<0.001), as well as serum markers for instance Ang Ⅱ(r=0.667, P<0.001) and VEGF(r=0.499, P<0.001). Furthermore, serum miR-221(AUC, 0.894; 95%CI, 0.833-0.955; P<0.001), Ang Ⅱ(AUC, 0.888; 95%CI, 0.828-0.949; P<0.001) and VEGF(AUC, 0.785; 95%CI, 0.695-0.875; P<0.001) had evidently diagnostic efficiency in DR, and miR-221 is the most effective among them.CONCLUSION: Serum miR-221 as a potential biomarker could be related to not only occurrence but also progression for DR in patients with T2D. However, a prospective clinical trial is warranted.
