Objective： To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application. Methods： Immunohistochemical stainin...Objective： To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application. Methods： Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues. Results： The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal （P〈0.05）. Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation. Conclusion： Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
The neurovascular unit plays a critical role in maintaining brain structure,function,and homeostasis.Following ischemic stroke,dysfunction and dysregulation of this unit contribute to nerve-blood vessel uncoupling.Int...The neurovascular unit plays a critical role in maintaining brain structure,function,and homeostasis.Following ischemic stroke,dysfunction and dysregulation of this unit contribute to nerve-blood vessel uncoupling.Intermittent theta-burst stimulation is a repetitive transcranial magnetic stimulation that operates within the theta wave range and can either promote or inhibit cortical excitability.Previous studies have shown that intermittent theta wave stimulation has neuroprotective effects,but the underlying mechanisms remain unclear.In this study,mice subjected to middle cerebral artery occlusion/reperfusion were treated with intermittent theta-burst stimulation.The results showed that intermittent theta-burst stimulation significantly improved neurological function and motor recovery,reduced apoptosis in the peri-infarct region,and activated the PI3K/AKT/GSK3β/β-catenin signaling pathway.Additionally,intermittent theta-burst stimulation suppressed inflammation through the PI3K/AKT/GSK3βand NF-κB pathways.Notably,intermittent theta-burst stimulation strengthened A2 astrocyte-blood vessel coupling,and the effects of intermittent theta-burst stimulation were reversed by the PI3K inhibitor LY294002.These findings demonstrate that intermittent theta-burst stimulation promotes neurovascular unit remodeling and improves neurological outcomes by modulating microglia and astrocytes via the PI3K/AKT/GSK3βand NF-κB signaling pathways.展开更多
From the fruit of Rosa davidii Crep., eleven compounds were isolated and identified by spectral evidence, viz. 2 alpha, 3 beta, 19 beta -trihydroxyl-olean-12-en-28-oic acid (1), 2 alpha, 3 beta -dihydroxyl-urs-28 (13)...From the fruit of Rosa davidii Crep., eleven compounds were isolated and identified by spectral evidence, viz. 2 alpha, 3 beta, 19 beta -trihydroxyl-olean-12-en-28-oic acid (1), 2 alpha, 3 beta -dihydroxyl-urs-28 (13)-lactone (2), arjunic acid (3), euscaphic acid (4), 2 alpha, 3 beta -dihydroxyl-urs-12-en-28-oic acid (5), oleanolic acid (6), kaempferol (7), tiliroside (8), quercetin (9), daucosterol (10) and beta -sitosterol (11). Among them, 1 and 2 were new compounds.展开更多
Two new sterols, 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5,22-diene (1), 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5-ene (2), were isolated together with six known compounds, ergosta-5, 24(28)-dien-3 beta, 7...Two new sterols, 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5,22-diene (1), 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5-ene (2), were isolated together with six known compounds, ergosta-5, 24(28)-dien-3 beta, 7 alpha -diol (3), ergosta-5,24(28)-dien-3 beta, 7 beta, 16 beta -triol (4), beta -amyrone (5), beta -amyrin (6), 11 alpha, 12 alpha -epoxy-14-taraxeren-3-one (7), and 6-guaiene-4 alpha, 10 alpha -diol (8) from the EtOH extract of the bark of Amoora yunnanensis (H. L. Li) C. Y. Wu. Their structures were deduced on the basis of spectral data.展开更多
Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed a...Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice,and exploring the potential molecular mechanisms.Insulin resistance in mice was induced with a high fat diet for 16 weeks.Animals were then treated with three different doses of baicalin(100,200,and 400 mg·kg^(-1)·d^(-1)for 14 weeks.Fasting blood glucose,fasting serum insulin,glucose tolerance test(GTT),insulin tolerance test(ITT),and skeletal muscle lipid deposition were measured.Additionally,the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated.Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance.Moreover,insulin resistance was significantly reversed.Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle.The properties of baicalin were mediated,at least in part,by inhibition of the AMPK/ACC pathway,a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway,a key regulator of Glycogen synthesis.These data suggest that baicalin,at dose up to 400 mg·kg^(-1)·d^(-1),is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage,through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.展开更多
文摘Objective： To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application. Methods： Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues. Results： The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal （P〈0.05）. Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation. Conclusion： Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
基金supported by the National Key R&D Program of China,Nos.2021ZD0202805(to XX),2019YFA0709504(to XX)the National Natural Science Foundation of China,Nos.82172544(to YW),32471083(to XX),81972140(to JW),82272604(to HX),82102491(to SC)+1 种基金the Brain Science and Brain-Like Research Project of Shanghai Sixth People’s Hospital,No.ynnkxyb202410(to JZ)Shanghai Science and Technology Committee Sailing Program,No.23YF1403800(to LL).
文摘The neurovascular unit plays a critical role in maintaining brain structure,function,and homeostasis.Following ischemic stroke,dysfunction and dysregulation of this unit contribute to nerve-blood vessel uncoupling.Intermittent theta-burst stimulation is a repetitive transcranial magnetic stimulation that operates within the theta wave range and can either promote or inhibit cortical excitability.Previous studies have shown that intermittent theta wave stimulation has neuroprotective effects,but the underlying mechanisms remain unclear.In this study,mice subjected to middle cerebral artery occlusion/reperfusion were treated with intermittent theta-burst stimulation.The results showed that intermittent theta-burst stimulation significantly improved neurological function and motor recovery,reduced apoptosis in the peri-infarct region,and activated the PI3K/AKT/GSK3β/β-catenin signaling pathway.Additionally,intermittent theta-burst stimulation suppressed inflammation through the PI3K/AKT/GSK3βand NF-κB pathways.Notably,intermittent theta-burst stimulation strengthened A2 astrocyte-blood vessel coupling,and the effects of intermittent theta-burst stimulation were reversed by the PI3K inhibitor LY294002.These findings demonstrate that intermittent theta-burst stimulation promotes neurovascular unit remodeling and improves neurological outcomes by modulating microglia and astrocytes via the PI3K/AKT/GSK3βand NF-κB signaling pathways.
文摘Two new sterols, 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5,22-diene (1), 3 beta, 7 alpha, 16 beta -trihydroxy-stigmast-5-ene (2), were isolated together with six known compounds, ergosta-5, 24(28)-dien-3 beta, 7 alpha -diol (3), ergosta-5,24(28)-dien-3 beta, 7 beta, 16 beta -triol (4), beta -amyrone (5), beta -amyrin (6), 11 alpha, 12 alpha -epoxy-14-taraxeren-3-one (7), and 6-guaiene-4 alpha, 10 alpha -diol (8) from the EtOH extract of the bark of Amoora yunnanensis (H. L. Li) C. Y. Wu. Their structures were deduced on the basis of spectral data.
基金supported by a grant provided by Southeast University(No.9224007044)
文摘Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice,and exploring the potential molecular mechanisms.Insulin resistance in mice was induced with a high fat diet for 16 weeks.Animals were then treated with three different doses of baicalin(100,200,and 400 mg·kg^(-1)·d^(-1)for 14 weeks.Fasting blood glucose,fasting serum insulin,glucose tolerance test(GTT),insulin tolerance test(ITT),and skeletal muscle lipid deposition were measured.Additionally,the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated.Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance.Moreover,insulin resistance was significantly reversed.Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle.The properties of baicalin were mediated,at least in part,by inhibition of the AMPK/ACC pathway,a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway,a key regulator of Glycogen synthesis.These data suggest that baicalin,at dose up to 400 mg·kg^(-1)·d^(-1),is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage,through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.
