Objective:To investigate the effect ofα1-antitrypsin combined with bone marrow mesenchymal stem cells on retinopathy in diabetic rats and its mechanism.Methods:A model of diabetic retinopathy was established by intra...Objective:To investigate the effect ofα1-antitrypsin combined with bone marrow mesenchymal stem cells on retinopathy in diabetic rats and its mechanism.Methods:A model of diabetic retinopathy was established by intraperitoneal injection of streptozotocin.The 30 Wistar rats successfully modeled were randomly divided into a model group,a bone marrow mesenchymal stem cell group and a combined group(α1-antitrypsin combined with bone marrow Mesenchymal stem cells),the blood glucose and serum insulin levels of diabetic rats were measured 4 weeks after treatment.Enzyme-linked immunosorbent assay(ELISA)for measuring serum inflammatory factors IL-1β,IL-6 and TNF-α in rats.Observing the pathological morphology of rat retina under hematoxylin-eosin staining(HE).TUNEL staining to observe the apoptosis of rat retinal nerve cells.Immunohistochemical method to detect the expression level of CD45 in retinal tissue.Real-time fluorescence quantitative PCR was used to detect the expression of retinal vascular endothelial growth factor(VEGF),hypoxiainducible factor-1α(HIF-1α),and angiotensinⅡ(ANGⅡ)mRNA.Western blot was used to detect the expression of p38 MAPK/NF-κB signaling pathway-related proteins in the retinal tissue of each group of rats.Results:Compared with the control group,the rats in the model group had increased blood glucose,decreased insulin levels,increased serum IL-1β,IL-6,and TNF-α levels,and had obvious lesions in the retina.CD45 showed high expression in retinal tissue,VEGF,HIF-1α,ANGⅡ mRNA expression increased,p-p38,p-p65,p-IκBα protein expression increased(P<0.05).Compared with the model group,the bone marrow mesenchymal stem cell group and the combined group have decreased blood glucose,increased insulin levels,and decreased serum IL-1β,IL-6 and TNF-α levels.Retinopathy is improved,apoptosis of retinal nerve cells is reduced,CD45 expression in retinal tissue is reduced,VEGF,HIF-1α,ANGⅡ mRNA expression is decreased,and p-p38,p-p65,p-IκBα protein expression is decreased.Compared with the bone marrow mesenchymal stem cell group,the effect of the combined group was more obvious(P<0.05).Conclusion:α1-antitrypsin combined with bone marrow mesenchymal stem cell transplantation can improve the degree of retinopathy in diabetic rats.The mechanism may be related to the inhibition of p38 MAPK/NF-κB signaling pathway.展开更多
Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine(TCM)for conditions such as rheumatism,arthralgia,and gynecological ailments.It has been offici...Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine(TCM)for conditions such as rheumatism,arthralgia,and gynecological ailments.It has been officially recognized as a protected variety of TCM by the state.The aim of this study was to investigate the therapeutic potential of Qianjinba polysaccharide(QJBDT)in treating rheumatoid arthritis(RA)in mice,along with a preliminary exploration of its mechanisms for inhibiting RA in these animals.Kunming mice(KM)were randomly divided into several groups,including a normal group,a model group(LPS group),low-dose,medium-dose,and high-dose QJBDT groups,as well as a positive control group(TGP group),each consisting of 10 mice.To induce inflammation and create an RA model,type II collagen was injected into the right hind foot joint.Following a 7-day modeling period,various concentrations of QJBDT and the positive control drug total glycoside of peony were administered via gavage once a day for 21 consecutive days.Throughout the study,we monitored and recorded the mice's weight,measured foot swelling,and assessed the arthritis index on a weekly basis.We also conducted pathological examinations of joint tissues and analyzed the signal pathway of p38 mitogen-activated protein kinase(MAPK)as well as the protein expression of nuclear factor NF-κB in the mice’s right foot joint tissues.Additionally,we employed ELISA to detect the levels of interleukin-β(IL-β),IL-17,and tumor necrosis factor-α(TNF-α)in the mice’s serum.The results of this study revealed that QJBDT effectively reduced the degree of foot swelling and the arthritis index in collagen-induced arthritis mice while improving their weight loss(P<0.05).Furthermore,it alleviated the pathological damage observed in the mice’s joints.Notably,the expression of transcription factors p38 and NF-κB proteins was down-regulated(P<0.05),and the levels of inflammatory cytokines IL-β,IL-17,and TNF-αin the mice’s serum were decreased(P<0.05).In conclusion,this study demonstrated that polysaccharides could inhibit the expression of transcription factors p38 and NF-κB,reduce the production of inflammatory factors,and alleviate the progression of RA to a certain extent.展开更多
Skeletal muscle differentiation is a highly coordinated process that involves many cellular signaling pathways and microRNAs(miRNAs).A group of muscle-specific miRNAs has been reported to promote myogenesis by suppres...Skeletal muscle differentiation is a highly coordinated process that involves many cellular signaling pathways and microRNAs(miRNAs).A group of muscle-specific miRNAs has been reported to promote myogenesis by suppressing key signaling pathways for cell growth.However,the functional role and regulatory mechanism of most non-muscle-specific miRNAs with stage-specific changes during differentiation are largely unclear.Here,we describe the functional characterization of miR-101a/b,a pair of non-muscle-specific miRNAs that show the largest change among a group of transiently upregulated miRNAs during myogenesis in C2C12 cells.The overexpression of miR-101a/b inhibits myoblast differentiation by suppressing the p38/MAPK,Interferon Gamma,and Wnt pathways and enhancing the C/EBP pathway.Mef2a,a key protein in the p38/MAPK pathway,was identified as a direct target of miR-101a/b.Interestingly,we found that the long non-coding RNA(lncRNA)Malat1,which promotes muscle differentiation,interacts with miR-101a/b,and this interaction competes with Mef2a mRNA to relieve the inhibition of the p38/MAPK pathway during myogenesis.These results uncovered a“braking”role in differentiation of transiently upregulated miRNAs and provided new insights into the competing endogenous RNA(ceRNA)regulatory mechanism in myoblast differentiation and myogenesis.展开更多
基金Key Rearch and Development projects in Shaanxi Province(2019SF-084).
文摘Objective:To investigate the effect ofα1-antitrypsin combined with bone marrow mesenchymal stem cells on retinopathy in diabetic rats and its mechanism.Methods:A model of diabetic retinopathy was established by intraperitoneal injection of streptozotocin.The 30 Wistar rats successfully modeled were randomly divided into a model group,a bone marrow mesenchymal stem cell group and a combined group(α1-antitrypsin combined with bone marrow Mesenchymal stem cells),the blood glucose and serum insulin levels of diabetic rats were measured 4 weeks after treatment.Enzyme-linked immunosorbent assay(ELISA)for measuring serum inflammatory factors IL-1β,IL-6 and TNF-α in rats.Observing the pathological morphology of rat retina under hematoxylin-eosin staining(HE).TUNEL staining to observe the apoptosis of rat retinal nerve cells.Immunohistochemical method to detect the expression level of CD45 in retinal tissue.Real-time fluorescence quantitative PCR was used to detect the expression of retinal vascular endothelial growth factor(VEGF),hypoxiainducible factor-1α(HIF-1α),and angiotensinⅡ(ANGⅡ)mRNA.Western blot was used to detect the expression of p38 MAPK/NF-κB signaling pathway-related proteins in the retinal tissue of each group of rats.Results:Compared with the control group,the rats in the model group had increased blood glucose,decreased insulin levels,increased serum IL-1β,IL-6,and TNF-α levels,and had obvious lesions in the retina.CD45 showed high expression in retinal tissue,VEGF,HIF-1α,ANGⅡ mRNA expression increased,p-p38,p-p65,p-IκBα protein expression increased(P<0.05).Compared with the model group,the bone marrow mesenchymal stem cell group and the combined group have decreased blood glucose,increased insulin levels,and decreased serum IL-1β,IL-6 and TNF-α levels.Retinopathy is improved,apoptosis of retinal nerve cells is reduced,CD45 expression in retinal tissue is reduced,VEGF,HIF-1α,ANGⅡ mRNA expression is decreased,and p-p38,p-p65,p-IκBα protein expression is decreased.Compared with the bone marrow mesenchymal stem cell group,the effect of the combined group was more obvious(P<0.05).Conclusion:α1-antitrypsin combined with bone marrow mesenchymal stem cell transplantation can improve the degree of retinopathy in diabetic rats.The mechanism may be related to the inhibition of p38 MAPK/NF-κB signaling pathway.
基金Shandong Provincial Key Project of TCM Science and Technology(Grant No.2021Z051)Shandong Medical and Health Science and Technology Development Program(Grant No.202102040972)supported by Binzhou Medical College Student Innovation and Entrepreneurship Training Program(Grant No.X202210440354).
文摘Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine(TCM)for conditions such as rheumatism,arthralgia,and gynecological ailments.It has been officially recognized as a protected variety of TCM by the state.The aim of this study was to investigate the therapeutic potential of Qianjinba polysaccharide(QJBDT)in treating rheumatoid arthritis(RA)in mice,along with a preliminary exploration of its mechanisms for inhibiting RA in these animals.Kunming mice(KM)were randomly divided into several groups,including a normal group,a model group(LPS group),low-dose,medium-dose,and high-dose QJBDT groups,as well as a positive control group(TGP group),each consisting of 10 mice.To induce inflammation and create an RA model,type II collagen was injected into the right hind foot joint.Following a 7-day modeling period,various concentrations of QJBDT and the positive control drug total glycoside of peony were administered via gavage once a day for 21 consecutive days.Throughout the study,we monitored and recorded the mice's weight,measured foot swelling,and assessed the arthritis index on a weekly basis.We also conducted pathological examinations of joint tissues and analyzed the signal pathway of p38 mitogen-activated protein kinase(MAPK)as well as the protein expression of nuclear factor NF-κB in the mice’s right foot joint tissues.Additionally,we employed ELISA to detect the levels of interleukin-β(IL-β),IL-17,and tumor necrosis factor-α(TNF-α)in the mice’s serum.The results of this study revealed that QJBDT effectively reduced the degree of foot swelling and the arthritis index in collagen-induced arthritis mice while improving their weight loss(P<0.05).Furthermore,it alleviated the pathological damage observed in the mice’s joints.Notably,the expression of transcription factors p38 and NF-κB proteins was down-regulated(P<0.05),and the levels of inflammatory cytokines IL-β,IL-17,and TNF-αin the mice’s serum were decreased(P<0.05).In conclusion,this study demonstrated that polysaccharides could inhibit the expression of transcription factors p38 and NF-κB,reduce the production of inflammatory factors,and alleviate the progression of RA to a certain extent.
基金supported by the National Natural Science Foundation of China(31970604,31701116,31770879,31771459,31900903,81870449,81974436)the Major Research Plan of the National Natural Science Foundation of China(91940000)+1 种基金the Fundamental Research Funds for the Central Universities(20lgpy112)Science and Technology New Star in ZhuJiang Guangzhou City(201806010151).
文摘Skeletal muscle differentiation is a highly coordinated process that involves many cellular signaling pathways and microRNAs(miRNAs).A group of muscle-specific miRNAs has been reported to promote myogenesis by suppressing key signaling pathways for cell growth.However,the functional role and regulatory mechanism of most non-muscle-specific miRNAs with stage-specific changes during differentiation are largely unclear.Here,we describe the functional characterization of miR-101a/b,a pair of non-muscle-specific miRNAs that show the largest change among a group of transiently upregulated miRNAs during myogenesis in C2C12 cells.The overexpression of miR-101a/b inhibits myoblast differentiation by suppressing the p38/MAPK,Interferon Gamma,and Wnt pathways and enhancing the C/EBP pathway.Mef2a,a key protein in the p38/MAPK pathway,was identified as a direct target of miR-101a/b.Interestingly,we found that the long non-coding RNA(lncRNA)Malat1,which promotes muscle differentiation,interacts with miR-101a/b,and this interaction competes with Mef2a mRNA to relieve the inhibition of the p38/MAPK pathway during myogenesis.These results uncovered a“braking”role in differentiation of transiently upregulated miRNAs and provided new insights into the competing endogenous RNA(ceRNA)regulatory mechanism in myoblast differentiation and myogenesis.
