BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely use...BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus(MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.AIM To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU.METHODS Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis.RESULTS A total of 2853 proteins were identified, and these included 65 dysregulated(31 upregulated and 34 downregulated) proteins(fold change ratio ≥ 1.2). Gene Ontology(GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanismthrough which RWIS gives rise to SGU.CONCLUSION Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.展开更多
In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error cou...In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.展开更多
Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relations...Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.展开更多
Objective: To investigate effects of Cornus officinalis Total Glycosides (COTG) and Cornus Polysaccharide (CP) on myocardial protection and on expression of mitochondria biogenesis related gene of acute myocardial inf...Objective: To investigate effects of Cornus officinalis Total Glycosides (COTG) and Cornus Polysaccharide (CP) on myocardial protection and on expression of mitochondria biogenesis related gene of acute myocardial infarction (AMI) rats, Materials and Methods: Ninety-six SD rats of SPF level were randomly divided into 5 groups: sham operation group, model group, preventive treatment group, COTG treatment group, CP treatment group, and there were 12 cases in each one. By legating the left anterior descending branch of coronary artery method, acute myocardial infarction model was established. The rat of sham operation group and model group was intragastric administered with physiological saline;other groups were given with corresponding drugs. The cardiac function, the myocardial infarct area, the expression of mitochondrial biogenesis genes such as PGC-1α, PGC-1β, NRF-1mRNA and GSK-3β mRNA, GSK-3β Protein Expression were analyzed. Results: The results revealed that compared with model group, myocardial infarction size, LVDs, LVDd, LVESV, LVEDP, and -dp/dt decreased;LVSP increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05);LVEDV increased in preventive treatment group (p < 0.05), PGC 1 alpha, and PGC 1 beta;the NRF-1 mRNA expression increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with CP and COTG treatment group, PGClpha, beta PGC 1, the NRF-1 mRNA expression increased in preventive treatment group (p < 0.05). Compared with the sham operation group, GSK-3 beta mRNA and protein expression increased in model group, preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with model group, GSK-3 beta mRNA expression reduced in preventive treatment group, COTG treatment group, and CP treatment group (p Cornus officinalis total glycosides and Cornus polysaccharides can effectively protect myocardial mitochondria of acute myocardial infarction rats by activating GSK-3β signaling 展开更多
Objective： To investigate the neuroprotective effects of icariin on formaldehyde （FA）-treated human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. Methods： SH-SY5Y cells were divided into FA tre...Objective： To investigate the neuroprotective effects of icariin on formaldehyde （FA）-treated human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. Methods： SH-SY5Y cells were divided into FA treatment group, FA treatment group with icariin, and the control group. Cell viability, apoptosis, and morphological changes were determined by cell counting kit-8 （CCK 8）, flow cytometry, and confocal microscopy, respectively. The phosphorylation of Tau protein was examined by western blotting. Results： FA showed a half lethal dose （LD50） of 0.3 mmol/L in SH-SY5Y cells under the experimental conditions. Icariin （1-10 μ mol/L） prevented FA-induced cell death in SH-SY5Y cells in a dose-dependent manner, with the optimal effect observed at 5 μmol/L. After FA treatment, the absorbance in FA group was 1.31±0.05, while in the group of icariin （5μmol/L） was 1.63±0.05. Examination of cell morphology by confocal microscopy demonstrated that 5 μmol/L icariin significantly attenuated FA-induced cell injury （P〈0.05）. Additionally, icariin inhibited FA-induced cell apoptosis in SH-SY5Y cells. Results from western blotting showed that icariin suppressed FA-induced phosphorylation at Thr 181 and Ser 396 of Tau protein, while having no effect on the expression of the total Tau protein level. Furthermore, FA activated Tau kinase glycogen synthase kinase 3 beta （GSK-3β） by enhancement of Y216 phosphorylation, but icariin reduced Y216 phosphorylation and increased Ser 9 phosphorylation. Conclusion： Icariin protects SH-SY5Y cells from FA-induced injury possibly through the inhibition of GSK-3β -mediated Tau phosphoryiation.展开更多
基金Supported by National Natural Science Foundation of China,No.31501861Natural Science Foundation of Shandong Province,China,No.ZR2015CM013
文摘BACKGROUND Stress-induced gastric ulcer(SGU) is one of the most common visceral complications after trauma. Restraint water-immersion stress(RWIS) can cause serious gastrointestinal dysfunction and has been widely used to study the pathogenesis of SGU to identify medications that can cure the disease. The mediodorsal thalamic nucleus(MD) is the centre integrating visceral and physical activity and contributes to SGU induced by RWIS. Hence, the role of the MD during RWIS needs to be studied.AIM To screen for differentially expressed proteins in the MD of the RWIS rats to further elucidate molecular mechanisms of SGU.METHODS Male Wistar rats were selected randomly and divided into two groups, namely, a control group and an RWIS group. Gastric mucosal lesions of the sacrificed rats were measured using the erosion index and the proteomic profiles of the MD were generated through isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by Western blot analysis.RESULTS A total of 2853 proteins were identified, and these included 65 dysregulated(31 upregulated and 34 downregulated) proteins(fold change ratio ≥ 1.2). Gene Ontology(GO) analysis showed that most of the upregulated proteins are primarily related to cell division, whereas most of the downregulated proteins are related to neuron morphogenesis and neurotransmitter regulation. Ingenuity Pathway Analysis revealed that the dysregulated proteins are mainly involved in the neurological disease signalling pathways. Furthermore, our results indicated that glycogen synthase kinase-3 beta might be related to the central mechanismthrough which RWIS gives rise to SGU.CONCLUSION Quantitative proteomic analysis elucidated the molecular targets associated with the production of SGU and provides insights into the role of the MD. The underlying molecular mechanisms need to be further dissected.
基金the National Natural Science Foundation of China,No.30870876the Natural Science Foundation of Guangdong Province,No.815101700100005+2 种基金the Science and Technology Program of Guangdong Province,No.2005B60302004,2008B030301371,2009B030801368the Traditional Chinese Medicineand Combination of Traditional Chinese and Western Medicine Program of Guangzhou,No.2008A52the Medical and Health Scientific Research Program of Guangzhou,No.2009-YB-167
文摘In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.
基金partly supported by the National Natural Science Foundation of China,No.81370448,81570725
文摘Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.
文摘Objective: To investigate effects of Cornus officinalis Total Glycosides (COTG) and Cornus Polysaccharide (CP) on myocardial protection and on expression of mitochondria biogenesis related gene of acute myocardial infarction (AMI) rats, Materials and Methods: Ninety-six SD rats of SPF level were randomly divided into 5 groups: sham operation group, model group, preventive treatment group, COTG treatment group, CP treatment group, and there were 12 cases in each one. By legating the left anterior descending branch of coronary artery method, acute myocardial infarction model was established. The rat of sham operation group and model group was intragastric administered with physiological saline;other groups were given with corresponding drugs. The cardiac function, the myocardial infarct area, the expression of mitochondrial biogenesis genes such as PGC-1α, PGC-1β, NRF-1mRNA and GSK-3β mRNA, GSK-3β Protein Expression were analyzed. Results: The results revealed that compared with model group, myocardial infarction size, LVDs, LVDd, LVESV, LVEDP, and -dp/dt decreased;LVSP increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05);LVEDV increased in preventive treatment group (p < 0.05), PGC 1 alpha, and PGC 1 beta;the NRF-1 mRNA expression increased in preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with CP and COTG treatment group, PGClpha, beta PGC 1, the NRF-1 mRNA expression increased in preventive treatment group (p < 0.05). Compared with the sham operation group, GSK-3 beta mRNA and protein expression increased in model group, preventive treatment group, COTG treatment group, and CP treatment group (p < 0.05). Compared with model group, GSK-3 beta mRNA expression reduced in preventive treatment group, COTG treatment group, and CP treatment group (p Cornus officinalis total glycosides and Cornus polysaccharides can effectively protect myocardial mitochondria of acute myocardial infarction rats by activating GSK-3β signaling
基金Supported by the National Natural Science Foundation of China(No.81102683 and No.81173369)the Doctoral Fellowships of Ministry of Education of China(No.20120001110105 and No.20110001120055)Beijing Natural Science Foundation(No.7132210)
文摘Objective： To investigate the neuroprotective effects of icariin on formaldehyde （FA）-treated human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. Methods： SH-SY5Y cells were divided into FA treatment group, FA treatment group with icariin, and the control group. Cell viability, apoptosis, and morphological changes were determined by cell counting kit-8 （CCK 8）, flow cytometry, and confocal microscopy, respectively. The phosphorylation of Tau protein was examined by western blotting. Results： FA showed a half lethal dose （LD50） of 0.3 mmol/L in SH-SY5Y cells under the experimental conditions. Icariin （1-10 μ mol/L） prevented FA-induced cell death in SH-SY5Y cells in a dose-dependent manner, with the optimal effect observed at 5 μmol/L. After FA treatment, the absorbance in FA group was 1.31±0.05, while in the group of icariin （5μmol/L） was 1.63±0.05. Examination of cell morphology by confocal microscopy demonstrated that 5 μmol/L icariin significantly attenuated FA-induced cell injury （P〈0.05）. Additionally, icariin inhibited FA-induced cell apoptosis in SH-SY5Y cells. Results from western blotting showed that icariin suppressed FA-induced phosphorylation at Thr 181 and Ser 396 of Tau protein, while having no effect on the expression of the total Tau protein level. Furthermore, FA activated Tau kinase glycogen synthase kinase 3 beta （GSK-3β） by enhancement of Y216 phosphorylation, but icariin reduced Y216 phosphorylation and increased Ser 9 phosphorylation. Conclusion： Icariin protects SH-SY5Y cells from FA-induced injury possibly through the inhibition of GSK-3β -mediated Tau phosphoryiation.
