[目的]研究鹿红方改善心肌梗死后心肌纤维化的作用机制。[方法]采用冠状动脉结扎法制备心肌梗死后心肌纤维化模型。将60只SD大鼠随机分配至假手术组、模型组、鹿红方组以及培哚普利组,干预4周后用心脏彩色多普勒超声检查测量心脏结构和...[目的]研究鹿红方改善心肌梗死后心肌纤维化的作用机制。[方法]采用冠状动脉结扎法制备心肌梗死后心肌纤维化模型。将60只SD大鼠随机分配至假手术组、模型组、鹿红方组以及培哚普利组,干预4周后用心脏彩色多普勒超声检查测量心脏结构和左室射血分数,苏木精-伊红(hematoxylin-eosin,HE)染色、Masson和天狼星红染色观察心脏组织纤维化病理改变,免疫印迹检测心脏信号转导及转录激活因子3(signal transducer and activator of transcription 3,STAT3)分泌情况,酶联免疫吸附分析(enzymelinked immunosorbent assay,ELISA)检测血清促纤维化因子结缔组织生长因子(connective tissue growth factor,CTGF)、血小板反应蛋白-1(thrombospondin-1,TSP-1)、基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)的水平。[结果]心脏彩色多普勒超声检查提示,与模型组比较,鹿红方和培哚普利干预均可抑制左室舒张末容积和左室舒张末内径的增大,而且使左室射血分数明显提升(P<0.05)。与培哚普利组比较,鹿红方组改善心室不良扩大与提高左室射血分数作用相近。HE染色结果显示,与模型组比较,鹿红方组和培哚普利组异常形态的心肌细胞数目明显减少,细胞间质肿胀减轻,炎症细胞浸润减少。Masson和天狼星红染色结果显示,与模型组比较,鹿红方组和培哚普利组干预均可减轻心肌纤维化病变程度。鹿红方组改善上述心肌病理改变和减轻心肌纤维化作用与培哚普利组相近。免疫印迹检测显示,与模型组比较,鹿红方和培哚普利干预均可增加心肌STAT3分泌(P<0.05),鹿红方组促进心肌分泌STAT3的作用与培哚普利组相近,差异无统计学意义(P>0.05)。ELISA结果显示,与模型组比较,鹿红方组与培哚普利组CTGF、TSP-1、TIMP-1水平显著降低(P<0.05),鹿红方组抑制CTGF、TSP-1和TIMP-1分泌作用与培哚普利组相近,差异无统计学意义(P>0.05)。[结论]鹿红方可显著抑制心肌梗死后心肌纤维化,其机制与上调STAT3水平,抑制促纤维化因子CTGF、TSP-1和TIMP-1分泌有关。展开更多
Neutron capture therapy with Sulfur-33, similar to boron neutron capture therapy with Boron-10, is effective in treating some types of tumors including ocular melanoma. The key point in sulfur neutron capture therapy ...Neutron capture therapy with Sulfur-33, similar to boron neutron capture therapy with Boron-10, is effective in treating some types of tumors including ocular melanoma. The key point in sulfur neutron capture therapy is whether the neutron beam flux and the resonance capture cross section of ^(33)S(n;α)^(30) Si reaction at 13.5 keV can achieve the requirements of radiotherapy. In this research,the authors investigated the production of 13.5 keV neutron production and moderation based on an accelerator neutron source. A lithium glass detector was used to measure the neutron flux produced via near threshold^7 Li(p,n)~7 Be reaction using the time-of-flight method. Furthermore, the moderation effects of different kinds of materials were investigated using Monte Carlo simulation.展开更多
Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the...Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium（RPE）derived retinoid isomerohydrolase（RPE65）to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine,porcine and rodent LCA2 models. The recombinant AAV2.h RPE65v2 adenoassociated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively,could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful,it will lead the way to additional gene therapy attempts to cure monogenic,inherited retinopathies.展开更多
Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)a...Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.展开更多
Alzheimer＇s disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment...Alzheimer＇s disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment, q-his innovative approach will lead to the identification of new targets for the preparation of new effective drugs. Peroxisome proliferator-activated receptors and their ligands are the ideal candidates to reach the necessary breakthrough to defeat this complicate disease.展开更多
Objective:To observe the lipid-lowering effect of different transdermal absorption enhancers applied to the herbal cake-partitioned moxibustion in hyperlipidemia model rabbits,and to explore the possible mechanism.Met...Objective:To observe the lipid-lowering effect of different transdermal absorption enhancers applied to the herbal cake-partitioned moxibustion in hyperlipidemia model rabbits,and to explore the possible mechanism.Methods:Forty New-Zea I a nd rabbits were ran domly divided into 5 groups using the ran dom nu mber table method,with 8 rats in each group.Rabbits in the blank group were fed routinely with normal diet;rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model.Rabbits in the blank and the model groups were not treated.After the model was prepared,rabbits in the non-transdermal absorption enhancer group received herbal cake-partitioned moxibustion without transdermal absorption enhancer;rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively.After 4 weeks of treatment,serum was collected for enzyme-linked immunosorbent assay(ELISA),and the liver tissues were isolated for imm uno histochemistry,qua ntitative polymerase chain reactio n(qPCR)and Western-blotting(WB)detecti on.Results:Serum ELISA results showed that leptin was significantly decreased in the model group compared with the blank group(P<0.05);compared with the model group,lepti n was significa ntly in creased in the non-tran sdermal absorpti on enhanee。the laurocapram and the borneol groups(all P<0.05);compared with the non-transdermal absorption enhancer group,leptin was significantly increased in the laurocapram group and the borneol group(both P<0.05);there was no significant differenee in leptin between the laurocapram and the borneol groups(P>0.05).The qPCR results of rabbit liver tissues showed that the mRNA expressions of leptin,Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STOT3)in the model group were significantly lower than those in the blank group(all P<0.05);compared with the model group,the mRNA expressions of leptin,leptin receptor(LR),JAK2 and S1AT3 in the non-transdermal absorptio n enhan cer,the laurocapram and the born eol groups were significantly in creased(all P<0.05);compared with the non-transdermal absorption enhancer group,the mRNA expressions of leptin,LR,JAK2 and S77VT3 in the laurocapram and the bor neol groups were sign ificantly in creased(all P<0.05);compared with the laurocapram group,the mRNA expressi ons of lepti n,LR,JAK2 and SW3 in the bor neol group were significa ntly in creased(P<0.05).The trend of immun ohistochemistry and WB detecti on results was basically con siste nt with the qPCR assay results.The immuno histochemistry and WB detection results of phosphorylated JAK2(phospho-JAK2)and phosphorylated S7AT3(phospho-STAT3)were basically consistent with those of JAK2 and S7AT3.Conclusion:The molecular expression of Leptin/JAK"S7AT3 pathway in the hyperlipidemia model rabbits was decreased.The molecular expression of Leptin/JAK0STCT3 pathway was significantly increased after the herbal cake-partitioned moxibustion.The application of laurocapram and borneol,as transdermal absorption enhancers,in the herbal cake-partitioned moxibustion could more obviously up-regulate the factors of the Leptin/JAK^SIAT3 lipid-regulating pathway than the herbal cake-partitioned moxibustion alone.展开更多
文摘[目的]研究鹿红方改善心肌梗死后心肌纤维化的作用机制。[方法]采用冠状动脉结扎法制备心肌梗死后心肌纤维化模型。将60只SD大鼠随机分配至假手术组、模型组、鹿红方组以及培哚普利组,干预4周后用心脏彩色多普勒超声检查测量心脏结构和左室射血分数,苏木精-伊红(hematoxylin-eosin,HE)染色、Masson和天狼星红染色观察心脏组织纤维化病理改变,免疫印迹检测心脏信号转导及转录激活因子3(signal transducer and activator of transcription 3,STAT3)分泌情况,酶联免疫吸附分析(enzymelinked immunosorbent assay,ELISA)检测血清促纤维化因子结缔组织生长因子(connective tissue growth factor,CTGF)、血小板反应蛋白-1(thrombospondin-1,TSP-1)、基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)的水平。[结果]心脏彩色多普勒超声检查提示,与模型组比较,鹿红方和培哚普利干预均可抑制左室舒张末容积和左室舒张末内径的增大,而且使左室射血分数明显提升(P<0.05)。与培哚普利组比较,鹿红方组改善心室不良扩大与提高左室射血分数作用相近。HE染色结果显示,与模型组比较,鹿红方组和培哚普利组异常形态的心肌细胞数目明显减少,细胞间质肿胀减轻,炎症细胞浸润减少。Masson和天狼星红染色结果显示,与模型组比较,鹿红方组和培哚普利组干预均可减轻心肌纤维化病变程度。鹿红方组改善上述心肌病理改变和减轻心肌纤维化作用与培哚普利组相近。免疫印迹检测显示,与模型组比较,鹿红方和培哚普利干预均可增加心肌STAT3分泌(P<0.05),鹿红方组促进心肌分泌STAT3的作用与培哚普利组相近,差异无统计学意义(P>0.05)。ELISA结果显示,与模型组比较,鹿红方组与培哚普利组CTGF、TSP-1、TIMP-1水平显著降低(P<0.05),鹿红方组抑制CTGF、TSP-1和TIMP-1分泌作用与培哚普利组相近,差异无统计学意义(P>0.05)。[结论]鹿红方可显著抑制心肌梗死后心肌纤维化,其机制与上调STAT3水平,抑制促纤维化因子CTGF、TSP-1和TIMP-1分泌有关。
文摘Neutron capture therapy with Sulfur-33, similar to boron neutron capture therapy with Boron-10, is effective in treating some types of tumors including ocular melanoma. The key point in sulfur neutron capture therapy is whether the neutron beam flux and the resonance capture cross section of ^(33)S(n;α)^(30) Si reaction at 13.5 keV can achieve the requirements of radiotherapy. In this research,the authors investigated the production of 13.5 keV neutron production and moderation based on an accelerator neutron source. A lithium glass detector was used to measure the neutron flux produced via near threshold^7 Li(p,n)~7 Be reaction using the time-of-flight method. Furthermore, the moderation effects of different kinds of materials were investigated using Monte Carlo simulation.
文摘Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium（RPE）derived retinoid isomerohydrolase（RPE65）to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine,porcine and rodent LCA2 models. The recombinant AAV2.h RPE65v2 adenoassociated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively,could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful,it will lead the way to additional gene therapy attempts to cure monogenic,inherited retinopathies.
基金Supported by The National Institutes of Health,NO.DK080812
文摘Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.
基金supported by Intervento cofinanziato dal Fondo di Sviluppo e Coesione 2007-2013–APQ Ricerca Regione Puglia "Programma regionale a sostegno della specializzazione intelligente e della sostenibilitàsociale ed ambientale-FutureInResearch".Project ID:I2PCTF6
文摘Alzheimer＇s disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment, q-his innovative approach will lead to the identification of new targets for the preparation of new effective drugs. Peroxisome proliferator-activated receptors and their ligands are the ideal candidates to reach the necessary breakthrough to defeat this complicate disease.
文摘Objective:To observe the lipid-lowering effect of different transdermal absorption enhancers applied to the herbal cake-partitioned moxibustion in hyperlipidemia model rabbits,and to explore the possible mechanism.Methods:Forty New-Zea I a nd rabbits were ran domly divided into 5 groups using the ran dom nu mber table method,with 8 rats in each group.Rabbits in the blank group were fed routinely with normal diet;rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model.Rabbits in the blank and the model groups were not treated.After the model was prepared,rabbits in the non-transdermal absorption enhancer group received herbal cake-partitioned moxibustion without transdermal absorption enhancer;rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively.After 4 weeks of treatment,serum was collected for enzyme-linked immunosorbent assay(ELISA),and the liver tissues were isolated for imm uno histochemistry,qua ntitative polymerase chain reactio n(qPCR)and Western-blotting(WB)detecti on.Results:Serum ELISA results showed that leptin was significantly decreased in the model group compared with the blank group(P<0.05);compared with the model group,lepti n was significa ntly in creased in the non-tran sdermal absorpti on enhanee。the laurocapram and the borneol groups(all P<0.05);compared with the non-transdermal absorption enhancer group,leptin was significantly increased in the laurocapram group and the borneol group(both P<0.05);there was no significant differenee in leptin between the laurocapram and the borneol groups(P>0.05).The qPCR results of rabbit liver tissues showed that the mRNA expressions of leptin,Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STOT3)in the model group were significantly lower than those in the blank group(all P<0.05);compared with the model group,the mRNA expressions of leptin,leptin receptor(LR),JAK2 and S1AT3 in the non-transdermal absorptio n enhan cer,the laurocapram and the born eol groups were significantly in creased(all P<0.05);compared with the non-transdermal absorption enhancer group,the mRNA expressions of leptin,LR,JAK2 and S77VT3 in the laurocapram and the bor neol groups were sign ificantly in creased(all P<0.05);compared with the laurocapram group,the mRNA expressi ons of lepti n,LR,JAK2 and SW3 in the bor neol group were significa ntly in creased(P<0.05).The trend of immun ohistochemistry and WB detecti on results was basically con siste nt with the qPCR assay results.The immuno histochemistry and WB detection results of phosphorylated JAK2(phospho-JAK2)and phosphorylated S7AT3(phospho-STAT3)were basically consistent with those of JAK2 and S7AT3.Conclusion:The molecular expression of Leptin/JAK"S7AT3 pathway in the hyperlipidemia model rabbits was decreased.The molecular expression of Leptin/JAK0STCT3 pathway was significantly increased after the herbal cake-partitioned moxibustion.The application of laurocapram and borneol,as transdermal absorption enhancers,in the herbal cake-partitioned moxibustion could more obviously up-regulate the factors of the Leptin/JAK^SIAT3 lipid-regulating pathway than the herbal cake-partitioned moxibustion alone.
