[Objectives]This study aimed to investigate the intervention effects of ethanol extract of Laggera alata(D.Don)Sch.Bip.ex Oliv on cirrhotic rats with ascites.[Methods]A total of 100 male SD rats of SPF grade were used...[Objectives]This study aimed to investigate the intervention effects of ethanol extract of Laggera alata(D.Don)Sch.Bip.ex Oliv on cirrhotic rats with ascites.[Methods]A total of 100 male SD rats of SPF grade were used.Rat models of cirrhosis and ascites were established.After the last administration,the amount of peritoneal fluid was measured,and the blood of each rat tested was collected for determination of serum AST,ALT and ALB levels,serum K+concentration and plasma Ald level.[Results]In ascitic cirrhotic rats,the livers showed obvious enlargement,the surface of the livers was uneven,and nodules were visible.Compared with the blank group,the amount of peritoneal fluid in the model group increased significantly(P<0.01);and compared with the model group,the amounts of peritoneal fluid in the high and medium-dose ethanol extract groups reduced significantly(P<0.01).Compared with the blank group,the serum ALT and AST levels in the model group increased significantly(P<0.01);and compared with the model group,the serum ALT and AST levels in the high-dose ethanol extract group decreased significantly(P<0.05).Compared with the blank group,the serum K+concentration in the positive group reduced(P<0.05);no significant difference was found in serum K+concentration between the ethanol extract administration groups and the blank group(P>0.05).Compared with the blank group,the plasma Ald levels in the high-dose ethanol extract group and the positive group reduced(P<0.05);and there was no significant difference in serum K+concentration between the rest groups and the blank group(P>0.05).[Conclusions]In the ethanol extract administration groups,the amounts of peritoneal fluid significantly reduced,the serum ALT and AST reduced,and the liver functions improved to a certain extent,indicating that the ethanol extract of L.alata(D.Don)Sch.Bip.ex Oliv has a better correction effect on electrolyte disturbances in cirrhotic rats with ascites.展开更多
The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities o...The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.展开更多
目的探讨Yes相关蛋白(YAP)在血管紧张素Ⅱ(AngⅡ)诱导的心肌纤维化中的作用及其机制。方法C57/B6小鼠30只,随机分为观察组、盐水组和模型组[腹腔注射AngⅡ1.5 mg/(kg·d)]4周,构建心肌纤维化模型,每组10只。将出生1~3 d SD乳鼠,差...目的探讨Yes相关蛋白(YAP)在血管紧张素Ⅱ(AngⅡ)诱导的心肌纤维化中的作用及其机制。方法C57/B6小鼠30只,随机分为观察组、盐水组和模型组[腹腔注射AngⅡ1.5 mg/(kg·d)]4周,构建心肌纤维化模型,每组10只。将出生1~3 d SD乳鼠,差速贴壁法提取原代心肌成纤维细胞(CF),随机分为4组,对照组、AngⅡ组、抑制组(20μmol/L PD98059加1μmol/L AngⅡ)和DMSO组,均刺激细胞24 h。Western blot检测α平滑肌肌动蛋白(α-SMA)和磷酸化细胞外信号调节激酶(p-ERK)及YAP表达。免疫荧光观察α-SMA表达;CCK-8检测CF增殖活力;Transwell实验检测细胞迁移能力。结果与观察组相比,模型组小鼠p-ERK(1.02±0.09 vs 0.61±0.15)及YAP(1.00±0.10 vs 0.63±0.05)表达明显升高(P<0.01)。与对照组比较,AngⅡ组CF的α-SMA荧光强度、A值及迁移细胞明显升高(P<0.05);抑制组上述指标较AngⅡ组明显降低(P<0.05)。与对照组比较,AngⅡ组CF的p-ERK、总YAP、核YAP表达明显升高(P<0.05),抑制组CF的p-ERK(0.64±0.08 vs 1.12±0.09)、总YAP(0.67±0.06 vs 1.06±0.11)、核YAP(0.84±0.20 vs 1.32±0.12)表达较AngⅡ组明显降低(P<0.05,P<0.01)。结论AngⅡ可能通过激活ERK与YAP信号通路诱导心肌纤维化。展开更多
AIM： To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats. METHODS： The streptozotocin （STZ）-induced diabetic rats were randomly divided ...AIM： To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats. METHODS： The streptozotocin （STZ）-induced diabetic rats were randomly divided into 6 groups： diabetes mellitus （DM） group （saline, 3 μL/eye）; RC28-E at low （0.33 μg/μL, 3 μL）, medium （1 μg/μL, 3 μL）, and high （3 μg/μL, 3 μL） dose groups; vascular endothelial growth factor （VEGF） Trap group （1 μg/μL, 3 μL）; fibroblast growth factor （FGF） Trap group （1 μg/μL, 3 μL）. Normal control group was included. At week 1 and 4 following diabetic induction, the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining. Glial fibrillary acidic protein （GFAP） expression was examined by immunofluorescence. Blood-retinal barrier （BRB） breakdown was assessed by Evans blue assay. Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy （TEM）. Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay （ELISA）. The retinal expression of intercellular cell adhesion molecule-1 （ICAM-1）, tumor necrosis factor-α （TNF-α）, VEGF and FGF genes was examined by quantitative polymerase chain reaction （qPCR）. RESULTS： TUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap （all P〈0.05）, the effects of medium and high dose RC28-E or FGF Trap were greater than VEGF Trap （P〈0.01）. GFAP staining suggested that reactive gliosis was substantially inhibited in all RC28-E and VEGF Trap groups, but the inhibition in FGF Trap group was not as prominent. Evans blue assay demonstrated that only high dose RC28-E could significantly reduce vascular leakage in early diabetic retina （P〈0.01）. TEM revealed that the ultrastructures in choroidal and retinal vessels were damaged in early diabetic retina, which was ameliorated to differential extents by each drug. The expression of VEGF and FGF2 proteins was significantly upregulated in early diabetic retina, and normalized by RC28-E at all dosages and by the corresponding Traps. The upregulation of ICAM-1 and TNF-α in diabetic retina was substantially suppressed by RC28-E and positive control drugs. CONCLUSION： Dual blockade of VEGF and FGF2 by RC28-E generates remarkable protective effects, including anti-apoptosis, anti-gliosis, anti-leakage, and improving ultrastructures and proinflammatory microenvironment, in early diabetic retina, thereby supporting further development of RC28-E into a novel and effective drug to diabetic retinopathy （DR）.展开更多
[Objectives]To optimize the extraction process of polysaccharide in Embelia parviflora Wall.by response surface methodology,and to study the antioxidant activity in vitro of polysaccharide in E.parviflora,so as to pro...[Objectives]To optimize the extraction process of polysaccharide in Embelia parviflora Wall.by response surface methodology,and to study the antioxidant activity in vitro of polysaccharide in E.parviflora,so as to provide a basis for the further development and utilization of E.parviflora.[Methods]The solid-to-liquid ratio,extraction temperature,extraction time and extraction times were used as single factors to investigate the effects.On this basis,the response surface methodology(RSM)was used to optimize the extraction process of polysaccharide in E.parviflora.DPPH and ABTS free radicals were used to investigate the antioxidant capacity of polysaccharide in E.parviflora.[Results]The optimal solid-to-liquid ratio for extraction of polysaccharide from E.parviflora was 32∶1(mL/g),extraction temperature was 77℃,and extraction time was 36 min.The IC50 values of DPPH and ABTS were 0.04 and 0.03 mg/mL,respectively.[Conclusions]The optimized extraction process of polysaccharide in E.parviflora is stable,the extraction rate is high,and has strong antioxidant activity.It is expected to provide a reference for the industrial extraction of polysaccharide from E.parviflora.展开更多
基金Guangxi Young and Middle-aged University Teachers'Scientific Research Ability Enhancement Project(No.2019KY0341)Foundation of Administration of Traditional Chinese Medicine of Guangxi Zhuang Autonomous Region(No.GZZC2019147)+2 种基金Youth Foundation of Guangxi University of Chinese Medicine(No.2019QN036)University-level Scientific Research Project of Youjiang Medical University for Nationalities(yy2018ky018)Scientific Research Laboratories of National Administration of Traditional Chinese Medicine(Level III):Chemistry and Quality Analysis Laboratory of Chinese(Zhuang)Medicine(Guo Zhong Yi Yao Fa 2009[21]).
文摘[Objectives]This study aimed to investigate the intervention effects of ethanol extract of Laggera alata(D.Don)Sch.Bip.ex Oliv on cirrhotic rats with ascites.[Methods]A total of 100 male SD rats of SPF grade were used.Rat models of cirrhosis and ascites were established.After the last administration,the amount of peritoneal fluid was measured,and the blood of each rat tested was collected for determination of serum AST,ALT and ALB levels,serum K+concentration and plasma Ald level.[Results]In ascitic cirrhotic rats,the livers showed obvious enlargement,the surface of the livers was uneven,and nodules were visible.Compared with the blank group,the amount of peritoneal fluid in the model group increased significantly(P<0.01);and compared with the model group,the amounts of peritoneal fluid in the high and medium-dose ethanol extract groups reduced significantly(P<0.01).Compared with the blank group,the serum ALT and AST levels in the model group increased significantly(P<0.01);and compared with the model group,the serum ALT and AST levels in the high-dose ethanol extract group decreased significantly(P<0.05).Compared with the blank group,the serum K+concentration in the positive group reduced(P<0.05);no significant difference was found in serum K+concentration between the ethanol extract administration groups and the blank group(P>0.05).Compared with the blank group,the plasma Ald levels in the high-dose ethanol extract group and the positive group reduced(P<0.05);and there was no significant difference in serum K+concentration between the rest groups and the blank group(P>0.05).[Conclusions]In the ethanol extract administration groups,the amounts of peritoneal fluid significantly reduced,the serum ALT and AST reduced,and the liver functions improved to a certain extent,indicating that the ethanol extract of L.alata(D.Don)Sch.Bip.ex Oliv has a better correction effect on electrolyte disturbances in cirrhotic rats with ascites.
基金financially supported by the National Key Research and Development Program of China(2018YFA0703003)National Natural Science Foundation of China(82072429,52125501,82371590)+6 种基金the Program for Innovation Team of Shaanxi Province(2023-CX-TD-17)the Key Research&Development Program of Shaanxi Province(2024SF-YBXM-355,2020SF-093,2021LLRH-08)the Natural Science Foundation of Henan Province(222300420358)the Postdoctoral Project of Shaanxi Province(2023BSHYDZZ30)the Postdoctoral Fellowship Program of CPSF(GZB20230573)the Institutional Foundation of the First Affiliated Hospital of Xi’an Jiaotong University(2019ZYTS-02)the Fundamental Research Funds for the Central Universities.
文摘The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.
文摘目的探讨Yes相关蛋白(YAP)在血管紧张素Ⅱ(AngⅡ)诱导的心肌纤维化中的作用及其机制。方法C57/B6小鼠30只,随机分为观察组、盐水组和模型组[腹腔注射AngⅡ1.5 mg/(kg·d)]4周,构建心肌纤维化模型,每组10只。将出生1~3 d SD乳鼠,差速贴壁法提取原代心肌成纤维细胞(CF),随机分为4组,对照组、AngⅡ组、抑制组(20μmol/L PD98059加1μmol/L AngⅡ)和DMSO组,均刺激细胞24 h。Western blot检测α平滑肌肌动蛋白(α-SMA)和磷酸化细胞外信号调节激酶(p-ERK)及YAP表达。免疫荧光观察α-SMA表达;CCK-8检测CF增殖活力;Transwell实验检测细胞迁移能力。结果与观察组相比,模型组小鼠p-ERK(1.02±0.09 vs 0.61±0.15)及YAP(1.00±0.10 vs 0.63±0.05)表达明显升高(P<0.01)。与对照组比较,AngⅡ组CF的α-SMA荧光强度、A值及迁移细胞明显升高(P<0.05);抑制组上述指标较AngⅡ组明显降低(P<0.05)。与对照组比较,AngⅡ组CF的p-ERK、总YAP、核YAP表达明显升高(P<0.05),抑制组CF的p-ERK(0.64±0.08 vs 1.12±0.09)、总YAP(0.67±0.06 vs 1.06±0.11)、核YAP(0.84±0.20 vs 1.32±0.12)表达较AngⅡ组明显降低(P<0.05,P<0.01)。结论AngⅡ可能通过激活ERK与YAP信号通路诱导心肌纤维化。
文摘AIM： To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats. METHODS： The streptozotocin （STZ）-induced diabetic rats were randomly divided into 6 groups： diabetes mellitus （DM） group （saline, 3 μL/eye）; RC28-E at low （0.33 μg/μL, 3 μL）, medium （1 μg/μL, 3 μL）, and high （3 μg/μL, 3 μL） dose groups; vascular endothelial growth factor （VEGF） Trap group （1 μg/μL, 3 μL）; fibroblast growth factor （FGF） Trap group （1 μg/μL, 3 μL）. Normal control group was included. At week 1 and 4 following diabetic induction, the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining. Glial fibrillary acidic protein （GFAP） expression was examined by immunofluorescence. Blood-retinal barrier （BRB） breakdown was assessed by Evans blue assay. Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy （TEM）. Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay （ELISA）. The retinal expression of intercellular cell adhesion molecule-1 （ICAM-1）, tumor necrosis factor-α （TNF-α）, VEGF and FGF genes was examined by quantitative polymerase chain reaction （qPCR）. RESULTS： TUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap （all P〈0.05）, the effects of medium and high dose RC28-E or FGF Trap were greater than VEGF Trap （P〈0.01）. GFAP staining suggested that reactive gliosis was substantially inhibited in all RC28-E and VEGF Trap groups, but the inhibition in FGF Trap group was not as prominent. Evans blue assay demonstrated that only high dose RC28-E could significantly reduce vascular leakage in early diabetic retina （P〈0.01）. TEM revealed that the ultrastructures in choroidal and retinal vessels were damaged in early diabetic retina, which was ameliorated to differential extents by each drug. The expression of VEGF and FGF2 proteins was significantly upregulated in early diabetic retina, and normalized by RC28-E at all dosages and by the corresponding Traps. The upregulation of ICAM-1 and TNF-α in diabetic retina was substantially suppressed by RC28-E and positive control drugs. CONCLUSION： Dual blockade of VEGF and FGF2 by RC28-E generates remarkable protective effects, including anti-apoptosis, anti-gliosis, anti-leakage, and improving ultrastructures and proinflammatory microenvironment, in early diabetic retina, thereby supporting further development of RC28-E into a novel and effective drug to diabetic retinopathy （DR）.
基金National Natural Science Foundation of China(81660701)Natural Science Foundation of Guangxi(2016GXNSFAA380148)+1 种基金Scientific Research Innovation Program of Guangxi University of Chinese Medicine(YJSZ201712)Program of Key Laboratory for Purification and Quality Analysis of TCM Extraction in Guangxi Universities(Gui Jiao Ke Yan[2014]No.6).
文摘[Objectives]To optimize the extraction process of polysaccharide in Embelia parviflora Wall.by response surface methodology,and to study the antioxidant activity in vitro of polysaccharide in E.parviflora,so as to provide a basis for the further development and utilization of E.parviflora.[Methods]The solid-to-liquid ratio,extraction temperature,extraction time and extraction times were used as single factors to investigate the effects.On this basis,the response surface methodology(RSM)was used to optimize the extraction process of polysaccharide in E.parviflora.DPPH and ABTS free radicals were used to investigate the antioxidant capacity of polysaccharide in E.parviflora.[Results]The optimal solid-to-liquid ratio for extraction of polysaccharide from E.parviflora was 32∶1(mL/g),extraction temperature was 77℃,and extraction time was 36 min.The IC50 values of DPPH and ABTS were 0.04 and 0.03 mg/mL,respectively.[Conclusions]The optimized extraction process of polysaccharide in E.parviflora is stable,the extraction rate is high,and has strong antioxidant activity.It is expected to provide a reference for the industrial extraction of polysaccharide from E.parviflora.
