Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells.Herein,we constructed a PEGylated dendritic ep...Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells.Herein,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)models.Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen secretion.Besides,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating them.As a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.展开更多
The purpose of this article was to explore the effects of gold nanoparticles(GNPs)and silver nano-particles(SNPs)with different cytotoxicities on human dermal fibroblasts(HDFs)at the metabolic level.First,~20 nm of GN...The purpose of this article was to explore the effects of gold nanoparticles(GNPs)and silver nano-particles(SNPs)with different cytotoxicities on human dermal fibroblasts(HDFs)at the metabolic level.First,~20 nm of GNPs and SNPs were prepared,and their effects on the proliferation of HDFs were evaluated.Then,a metabolomics technique was used to analyse the effects of GNPs and SNPs on the expression profiles of metabolites in HDFs after 4,8 and 24h of treatment.Furthermore,the key metabolites and key metabolic pathways involved in the interaction of GNPs and SNPs with HDFs were identified through expression pattern analysis and metabolic pathway analysis of differentially expressed metabolites and were finally verified by experiments.The results of the cytotoxicity experiments showed that there was no cytotoxicity after the treatment of GNPs for 72 h,while the cytotoxicity of the SNPs reached grade 1 after 72 h.By using metabolomics analysis,29,30 and 27 metabolites were shown to be differentially expressed in HDFs after GNP treatment,while SNPs induced the differential expression of 13,33 and 22 metabolites after 4,8 and 24h of treatment,respectively.Six and four candidate key metabolites in the GNP and SNP groups were identified by expression pattern analysis and metabolic pathway analysis,respec-tively.The key metabolic pathways in the GNP and SNP groups were identified as the glutathione metabolic pathway(the key metabolite of which was glutathione)and the citrate cycle pathway(the key metabolite of which was malic acid).Based on the experiments used to verify the key metabolites and key metabolic pathways,it was found that the increase in glutathione after GNP treatment might trigger an oxidative stress protection mechanism and thus avoid cytotoxicity.After exposure to SNPs,the citric acid content was increased,mainly through the citrate cycle path-way,thereby inhibiting the synthesis of malic acid to affect the formation of ATP and finally leading to cytotoxicity.展开更多
Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and ...Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.展开更多
BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are ...BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.展开更多
Objective: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. Design: Retrospective and observational case series. Methods: We review...Objective: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. Design: Retrospective and observational case series. Methods: We reviewed 41 patients (41 eyes) suffering exposure of orbital implants from Jan. 2000 to June 2006. The study group patients with mild exposure received com-bined treatment with bFGF and antibiotic drops, and while the control group patients with mild exposure were treated with anti-biotic drops only. The study group patients with moderate and severe exposure received combined treatment with bFGF and antibiotic drops, and after 2 months they were subjected to amniotic membrane transplantation, while the control group patients with moderate and severe exposure underwent amniotic membrane transplantation after using antibiotic drops. Observation of the growth of conjunctival epithelium and comparison of the healing rate of the two groups. Results: The healing rates of the mild, moderate and severe exposure study group were 100% and 92.3%. The healing rates of the mild, moderate and severe exposure control group were 55.6% and 66.7% respectively. The difference of the healing rates of the mild exposure study group and the control group was significant (P=0.033). And the difference of the healing rates of the moderate and severe exposure study group and the control group was not significant (P=0.167). Conclusion: bFGF may promote obviously the healing of orbital implant exposure, particularly it can be the first choice for the treatment of mild degree exposure. For the moderate and severe cases, it can be administered before surgical repair to enhance neovascularization and will tend to increase the success rate of surgical repair.展开更多
背景:增生性瘢痕是以成纤维细胞过度增殖、表皮增厚和角质层功能不良为特征的皮肤纤维化疾病,目前其具体发病机制仍不清楚。目的:基于生物信息学筛选增生性瘢痕相关数据集的核心(Hub)基因及重要信号通路,再用细胞实验加以验证,预测对其...背景:增生性瘢痕是以成纤维细胞过度增殖、表皮增厚和角质层功能不良为特征的皮肤纤维化疾病,目前其具体发病机制仍不清楚。目的:基于生物信息学筛选增生性瘢痕相关数据集的核心(Hub)基因及重要信号通路,再用细胞实验加以验证,预测对其可能有治疗作用的小分子药物。方法:从基因表达综合数据库搜索增生性瘢痕相关的数据集,通过R软件筛选差异表达基因,对差异表达基因进行基因本体论和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Gnomes,KEGG)富集分析,使用String在线平台构建差异表达基因的蛋白质相互作用网络,然后分别利用Cytoscape软件中的Cytohubba和MCODE插件筛选出蛋白质相互作用网络中的关键基因和核心模块,进一步将上述关键基因和构成核心模块的基因求交集得到Hub基因,通过荧光定量PCR验证Hub基因mRNA在人增生性瘢痕与正常皮肤表皮干细胞中的表达差异,并利用人类蛋白图谱中组织学数据验证Hub基因编码蛋白在2种组织中表达量和分布的差异,最后用connectivity map数据库预测针对增生性瘢痕的潜在作用药物。结果与结论:①筛选出的差异表达基因中上调基因102个、下调基因702个,基因本体论和KEGG分析结果显示,富集的信号通路及生物学过程主要涉及紧密连接、花生四烯酸代谢、细胞外基质受体交互、表皮发育和角质化等;②取交集得到8个Hub基因与调控胆固醇代谢的甲羟戊酸途径密切相关,分别是HMGCS1、DHCR7、MSMO1、FDPS、MVK、HMGCR、MVD和ACAT2;③荧光定量PCR结果显示,相比正常皮肤组,增生性瘢痕组HMGCS1、DHCR7、MSMO1、FDPS、HMGCR、MVD和ACAT2 mRNA的表达均显著下降(P<0.05),而MVK mRNA的表达无明显变化(P>0.05);④除MVK外,其余Hub基因编码蛋白在正常皮肤组织中表达水平均高于增生性瘢痕组织(P<0.05);⑤评分排列前10的候选药物包括蛋白激酶A抑制剂(H-89)、丝氨酸蛋白酶抑制剂(Dabigatran-Etexilate)、FLT3抑制剂(舒尼替尼)等,其中白藜芦醇和β-谷甾醇均为植物来源;⑥提示与甲羟戊酸代谢途径密切相关的Hub基因可能通过调控脂质代谢影响表皮结构与功能,这可能是增生性瘢痕的重要发病机制之一,此次研究筛选的小分子化合物可作为治疗增生性瘢痕的候选药物。展开更多
Fibroblast growth factor 21(FGF21)has been identified as an important regulator of carbohydrate and lipid metabolism,which plays an important role for metabolic regulation,particularly under conditions of energy depri...Fibroblast growth factor 21(FGF21)has been identified as an important regulator of carbohydrate and lipid metabolism,which plays an important role for metabolic regulation,particularly under conditions of energy deprivation or stress conditions.Dairy cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early lactation.It has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of lactation.This finding suggests that FGF21 might exert similar functions in dairy cows than in other species,such as mice or humans.However,the role of FGF21 in dairy cows has been less investigated so far.Following a brief summary of the previous findings about the function of FGF21 in humans and mice,the present review aims to present the current state of knowledge about the role of FGF21 in dairy cows.The first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy cows.In the second part,the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is addressed.In the third part,findings of exogenous FGF21 application on metabolism in dairy cows are reported.Finally,the potential relevance of FGF21 in dairy cows is discussed.It is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy cows.However,further studies are needed for a better understanding of the functions of FGF21 in dairy cows.展开更多
基金supported by the National Science and Technology Major Project of China(2023YFB3810004)the National Natural Science Foundation of China(32271445,52103175,32271382,32101145)+4 种基金the National Key Research and Development Program of China(2022YFC2009900)Department of Science and Technology of Sichuan Province(24NSFJQ0167,China)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21013,China)Post-Doctor Research Project,West China Hospital,Sichuan University(2021HXBH055,2021HXBH057,China)China Postdoctoral Science Foundation(2021M692314).
文摘Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells.Herein,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)models.Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen secretion.Besides,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating them.As a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.
基金supported by National Natural Science Foundation of China(31600816)Natural Science Foundation of Jiangsu Province(BK20150599)State Key Laboratory for Mechanical Behavior of Materials of Xi’an Jiaotong University(20161804).
文摘The purpose of this article was to explore the effects of gold nanoparticles(GNPs)and silver nano-particles(SNPs)with different cytotoxicities on human dermal fibroblasts(HDFs)at the metabolic level.First,~20 nm of GNPs and SNPs were prepared,and their effects on the proliferation of HDFs were evaluated.Then,a metabolomics technique was used to analyse the effects of GNPs and SNPs on the expression profiles of metabolites in HDFs after 4,8 and 24h of treatment.Furthermore,the key metabolites and key metabolic pathways involved in the interaction of GNPs and SNPs with HDFs were identified through expression pattern analysis and metabolic pathway analysis of differentially expressed metabolites and were finally verified by experiments.The results of the cytotoxicity experiments showed that there was no cytotoxicity after the treatment of GNPs for 72 h,while the cytotoxicity of the SNPs reached grade 1 after 72 h.By using metabolomics analysis,29,30 and 27 metabolites were shown to be differentially expressed in HDFs after GNP treatment,while SNPs induced the differential expression of 13,33 and 22 metabolites after 4,8 and 24h of treatment,respectively.Six and four candidate key metabolites in the GNP and SNP groups were identified by expression pattern analysis and metabolic pathway analysis,respec-tively.The key metabolic pathways in the GNP and SNP groups were identified as the glutathione metabolic pathway(the key metabolite of which was glutathione)and the citrate cycle pathway(the key metabolite of which was malic acid).Based on the experiments used to verify the key metabolites and key metabolic pathways,it was found that the increase in glutathione after GNP treatment might trigger an oxidative stress protection mechanism and thus avoid cytotoxicity.After exposure to SNPs,the citric acid content was increased,mainly through the citrate cycle path-way,thereby inhibiting the synthesis of malic acid to affect the formation of ATP and finally leading to cytotoxicity.
文摘Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.
基金the National Natural Science Foundation of China, No. 81600617
文摘BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.
文摘Objective: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. Design: Retrospective and observational case series. Methods: We reviewed 41 patients (41 eyes) suffering exposure of orbital implants from Jan. 2000 to June 2006. The study group patients with mild exposure received com-bined treatment with bFGF and antibiotic drops, and while the control group patients with mild exposure were treated with anti-biotic drops only. The study group patients with moderate and severe exposure received combined treatment with bFGF and antibiotic drops, and after 2 months they were subjected to amniotic membrane transplantation, while the control group patients with moderate and severe exposure underwent amniotic membrane transplantation after using antibiotic drops. Observation of the growth of conjunctival epithelium and comparison of the healing rate of the two groups. Results: The healing rates of the mild, moderate and severe exposure study group were 100% and 92.3%. The healing rates of the mild, moderate and severe exposure control group were 55.6% and 66.7% respectively. The difference of the healing rates of the mild exposure study group and the control group was significant (P=0.033). And the difference of the healing rates of the moderate and severe exposure study group and the control group was not significant (P=0.167). Conclusion: bFGF may promote obviously the healing of orbital implant exposure, particularly it can be the first choice for the treatment of mild degree exposure. For the moderate and severe cases, it can be administered before surgical repair to enhance neovascularization and will tend to increase the success rate of surgical repair.
文摘背景:增生性瘢痕是以成纤维细胞过度增殖、表皮增厚和角质层功能不良为特征的皮肤纤维化疾病,目前其具体发病机制仍不清楚。目的:基于生物信息学筛选增生性瘢痕相关数据集的核心(Hub)基因及重要信号通路,再用细胞实验加以验证,预测对其可能有治疗作用的小分子药物。方法:从基因表达综合数据库搜索增生性瘢痕相关的数据集,通过R软件筛选差异表达基因,对差异表达基因进行基因本体论和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Gnomes,KEGG)富集分析,使用String在线平台构建差异表达基因的蛋白质相互作用网络,然后分别利用Cytoscape软件中的Cytohubba和MCODE插件筛选出蛋白质相互作用网络中的关键基因和核心模块,进一步将上述关键基因和构成核心模块的基因求交集得到Hub基因,通过荧光定量PCR验证Hub基因mRNA在人增生性瘢痕与正常皮肤表皮干细胞中的表达差异,并利用人类蛋白图谱中组织学数据验证Hub基因编码蛋白在2种组织中表达量和分布的差异,最后用connectivity map数据库预测针对增生性瘢痕的潜在作用药物。结果与结论:①筛选出的差异表达基因中上调基因102个、下调基因702个,基因本体论和KEGG分析结果显示,富集的信号通路及生物学过程主要涉及紧密连接、花生四烯酸代谢、细胞外基质受体交互、表皮发育和角质化等;②取交集得到8个Hub基因与调控胆固醇代谢的甲羟戊酸途径密切相关,分别是HMGCS1、DHCR7、MSMO1、FDPS、MVK、HMGCR、MVD和ACAT2;③荧光定量PCR结果显示,相比正常皮肤组,增生性瘢痕组HMGCS1、DHCR7、MSMO1、FDPS、HMGCR、MVD和ACAT2 mRNA的表达均显著下降(P<0.05),而MVK mRNA的表达无明显变化(P>0.05);④除MVK外,其余Hub基因编码蛋白在正常皮肤组织中表达水平均高于增生性瘢痕组织(P<0.05);⑤评分排列前10的候选药物包括蛋白激酶A抑制剂(H-89)、丝氨酸蛋白酶抑制剂(Dabigatran-Etexilate)、FLT3抑制剂(舒尼替尼)等,其中白藜芦醇和β-谷甾醇均为植物来源;⑥提示与甲羟戊酸代谢途径密切相关的Hub基因可能通过调控脂质代谢影响表皮结构与功能,这可能是增生性瘢痕的重要发病机制之一,此次研究筛选的小分子化合物可作为治疗增生性瘢痕的候选药物。
文摘成纤维细胞生长因子23(fibroblast growth factor 23,FGF23)是骨细胞和成骨细胞来源的一种内分泌型信号蛋白,可通过成纤维细胞生长因子受体/α-Klotho复合物调节体内的血清磷酸盐和1,25-二羟维生素D水平,维持体内磷酸盐动态平衡。由于FGF23对骨矿物质稳态发挥了关键作用,其对慢性肾脏病的矿物质和骨代谢异常(chronic kidney disease-mineral and bone disorder,CKD-MBD)的影响及作用机制受到了研究人员的广泛关注。研究证实,FGF23通过直接或间接途径参与了骨矿物质的形成和骨代谢,对骨微结构和骨密度的改变有重要影响。目前,围绕FGF23进行治疗CKD-MBD的新药研究进展缓慢。中药因其治疗CKD-MBD疗效确切且价格低廉,已在临床广泛应用。近年来,研究人员对中药靶向调控FGF23治疗CKD-MBD进行了深入研究。笔者整理及分析了国内外近年来的相关文献,阐释了FGF23在CKD-MBD中的作用,并综述了中药靶向调控FGF23治疗CKD-MBD的研究进展,以期为临床应用中药治疗CKD-MBD提供新思路和理论基础。
文摘Fibroblast growth factor 21(FGF21)has been identified as an important regulator of carbohydrate and lipid metabolism,which plays an important role for metabolic regulation,particularly under conditions of energy deprivation or stress conditions.Dairy cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early lactation.It has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of lactation.This finding suggests that FGF21 might exert similar functions in dairy cows than in other species,such as mice or humans.However,the role of FGF21 in dairy cows has been less investigated so far.Following a brief summary of the previous findings about the function of FGF21 in humans and mice,the present review aims to present the current state of knowledge about the role of FGF21 in dairy cows.The first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy cows.In the second part,the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is addressed.In the third part,findings of exogenous FGF21 application on metabolism in dairy cows are reported.Finally,the potential relevance of FGF21 in dairy cows is discussed.It is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy cows.However,further studies are needed for a better understanding of the functions of FGF21 in dairy cows.
