There is still no effective therapy for muscle atrophy.It found that miR-194 was significantlydownregulated in muscle atrophy model.miR-194 could promote muscle differentiation,and also inhibit ubiquitin ligases.miR-1...There is still no effective therapy for muscle atrophy.It found that miR-194 was significantlydownregulated in muscle atrophy model.miR-194 could promote muscle differentiation,and also inhibit ubiquitin ligases.miR-194 loaded in gelatin nanosphere were injected into the muscle atrophy model to realize controlled release.展开更多
OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical fo...OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical for regulating the balance between protein synthesis and degradation during disuse/inactivity-induced muscle atrophy.The present study aimed to investigate whether natural product Icaritin(ICT)required PI3K/Akt signaling to exert counteractive effect on skeletal muscle atrophy following mechanical unloading.METHODS Two oral dosages of ICT(80and 120mg·kg-1·d-1)were administrated daily to adult male rats with or without daily injection of PI3K/Akt signaling inhibitor wortmannin(15μg·kg-1·d-1)during 28-d hindlimb suspension(HS).Ex vivo muscle functional testing,histological and immunohistochemical analysis were performed to determine the changes of soleus muscle function,mean muscle fiber cross-sectional area(CSA)and fiber type distribution.Western blot and real-time PCR analysis were also performed to evaluate the protein or mRNA expression of the markers involved in PI3K/Akt signaling pathway.RESULTS After 28-d HS,soleus muscle underwent profound muscle atrophy(-52.7% muscle mass vs.pre-HS baseline).The high dose ICT treatment significantly attenuated the decreases in soleus muscle mass(+22.6% vs.HS),muscle fiber CSA(+52.8% vs.HS),as well as the muscle functional testing parameters during the unloading.Molecularly,the high dose ICT treatment significantly attenuated the decreases in protein synthesis markers at protein levels(phosphorylation of Akt and its downstream proteins)during the unloading,whereas the increases in protein degradation markers at mRNA(atrogin-1and MuRF-1)and protein(nuclear FOXO1 and FOXO3a)levels during the unloading were significantly attenuated by the high dose ICT treatment.The low dose ICT treatment moderately attenuated the above changes induced by the unloading.Mechanistically,Wortmannin could abolish the above effects of ICT.CONCLUSION ICT requires participation of PI3K/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading in a dose-dependent manner.展开更多
Introduction Liver cirrhosis generally occurs with the hemodynamic changes during the portal vein hypertension and finally leads to the atrophy of the right lobe of the liver and hepatic failure<sup>[1]</sup&...Introduction Liver cirrhosis generally occurs with the hemodynamic changes during the portal vein hypertension and finally leads to the atrophy of the right lobe of the liver and hepatic failure<sup>[1]</sup>.According to the hemodynamic changes,a hypothesis has been proposed that the liver volume is related to the istribution of blood from the splenic vein（SV）that involves nutrition from spleen and pancreas<sup>[2,3]</sup>.The objective of the present paper is to simulate the blood flow in real models of portal vein hypertension and validate the hypothesis using computational fluid dynamics（CFD）method.Methods This study includes 2 patients with liver cirrhosis and a set of 4 normal subjects.展开更多
Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further su...Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further sup- port this link displaying deficits in working memory, learning, and memory performance. The risk factors for dia- betic cognitive dysfunction include vascular disease, hypoglycemia, hyperlipidemia, adiposity, lifestyle factors, and genetic factors. Using neuronimage technologies, diabetic patients with cognitive dysfunction shows whole brain atrophy, gray matter atrophy, hippocampal atrophy, and amygdala atrophy, increased ventricular volume and white matter volume, brain infarcts, impaired network integrity, microstructural abnormality, reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis mechanisms of type 2 diabetes with cognitive dys- function involve hyperglycemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apop- tosis, impaired neurogenesis, impaired blood-brain barrier, and disorder neurotransmitters. Some antidiabetic drugs and Traditional Chinese Medicine partly improve diabetic cognitive dysfunction, but more clinical investigations are demanded to verify their efficiencies and novel drugs are urgent need to develop. Large clinical studies will provide further evidences of risks factors and biomarkers for diabetic cognitive dysfunction. Both novel disease animal mod- els and advanced neuronimage technologies will help to investigate the exact pathogenesis mechanisms and to devel- op better therapeutic interventions and treatment.展开更多
文摘There is still no effective therapy for muscle atrophy.It found that miR-194 was significantlydownregulated in muscle atrophy model.miR-194 could promote muscle differentiation,and also inhibit ubiquitin ligases.miR-194 loaded in gelatin nanosphere were injected into the muscle atrophy model to realize controlled release.
基金The project supported by National Natural Science Foundation of China(81201406)Direct Grant for Research,The Chinese University of Hong Kong(4054138)
文摘OBJECTIVE Skeletal muscle undergoes rapid and profound atrophy in response to decreased mechanical loading,e.g.,limb immobilization and bed rest.Phosphatidylinositol 3 kinase(PI3K)/Akt signaling pathway is critical for regulating the balance between protein synthesis and degradation during disuse/inactivity-induced muscle atrophy.The present study aimed to investigate whether natural product Icaritin(ICT)required PI3K/Akt signaling to exert counteractive effect on skeletal muscle atrophy following mechanical unloading.METHODS Two oral dosages of ICT(80and 120mg·kg-1·d-1)were administrated daily to adult male rats with or without daily injection of PI3K/Akt signaling inhibitor wortmannin(15μg·kg-1·d-1)during 28-d hindlimb suspension(HS).Ex vivo muscle functional testing,histological and immunohistochemical analysis were performed to determine the changes of soleus muscle function,mean muscle fiber cross-sectional area(CSA)and fiber type distribution.Western blot and real-time PCR analysis were also performed to evaluate the protein or mRNA expression of the markers involved in PI3K/Akt signaling pathway.RESULTS After 28-d HS,soleus muscle underwent profound muscle atrophy(-52.7% muscle mass vs.pre-HS baseline).The high dose ICT treatment significantly attenuated the decreases in soleus muscle mass(+22.6% vs.HS),muscle fiber CSA(+52.8% vs.HS),as well as the muscle functional testing parameters during the unloading.Molecularly,the high dose ICT treatment significantly attenuated the decreases in protein synthesis markers at protein levels(phosphorylation of Akt and its downstream proteins)during the unloading,whereas the increases in protein degradation markers at mRNA(atrogin-1and MuRF-1)and protein(nuclear FOXO1 and FOXO3a)levels during the unloading were significantly attenuated by the high dose ICT treatment.The low dose ICT treatment moderately attenuated the above changes induced by the unloading.Mechanistically,Wortmannin could abolish the above effects of ICT.CONCLUSION ICT requires participation of PI3K/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading in a dose-dependent manner.
基金supported by National Science Foundation of China(51176152)Specialized Research Fund for the Doctoral Program of Higher Education(20120201110070)the Fundamental Research Funds for the Central University(xjj2012115)
文摘Introduction Liver cirrhosis generally occurs with the hemodynamic changes during the portal vein hypertension and finally leads to the atrophy of the right lobe of the liver and hepatic failure<sup>[1]</sup>.According to the hemodynamic changes,a hypothesis has been proposed that the liver volume is related to the istribution of blood from the splenic vein（SV）that involves nutrition from spleen and pancreas<sup>[2,3]</sup>.The objective of the present paper is to simulate the blood flow in real models of portal vein hypertension and validate the hypothesis using computational fluid dynamics（CFD）method.Methods This study includes 2 patients with liver cirrhosis and a set of 4 normal subjects.
文摘Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further sup- port this link displaying deficits in working memory, learning, and memory performance. The risk factors for dia- betic cognitive dysfunction include vascular disease, hypoglycemia, hyperlipidemia, adiposity, lifestyle factors, and genetic factors. Using neuronimage technologies, diabetic patients with cognitive dysfunction shows whole brain atrophy, gray matter atrophy, hippocampal atrophy, and amygdala atrophy, increased ventricular volume and white matter volume, brain infarcts, impaired network integrity, microstructural abnormality, reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis mechanisms of type 2 diabetes with cognitive dys- function involve hyperglycemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apop- tosis, impaired neurogenesis, impaired blood-brain barrier, and disorder neurotransmitters. Some antidiabetic drugs and Traditional Chinese Medicine partly improve diabetic cognitive dysfunction, but more clinical investigations are demanded to verify their efficiencies and novel drugs are urgent need to develop. Large clinical studies will provide further evidences of risks factors and biomarkers for diabetic cognitive dysfunction. Both novel disease animal mod- els and advanced neuronimage technologies will help to investigate the exact pathogenesis mechanisms and to devel- op better therapeutic interventions and treatment.
