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Objective To explore the association between PI3K polymorphisms in insulin signal transduction pathway and Alzheimer's disease (AD)risk.Methods There were three groups,including 112 cases for AD +T2D group,231 cases for only AD group,and 231 cases for healthy controls group.The polymorphisms in PI3K gene was sequenced by PCR and the concentration of PI3K in serum was tested by enzyme -linked immunosorbent assay (ELISA).Results Overall,there was significantly statistical difference in PI3K rs3730087 polymorphism among three groups (χ2 =20.99,P =0.000 3).The CC frequency of PI3K rs3730087 polymorphism in AD with T2D group and AD control group was significantly higher than that in the healthy control group.The PI3K protein level of differ-ent genotype was statistically significant (F =27.450,P <0.000 1).As for CC genotypes of PI3K rs3730087 poly-morphism,the PI3K protein level was statistically different among these three groups (F =8.096,P =0.000 6).Moreover,the PI3K protein level of the three groups was different (F =9.034,P =0.000 1),which in both AD group was lower as compared with healthy control group.Conclusion The study suggested that CC genotype of PI3K rs3730087 polymorphism in insulin signaling transduction pathway might be a risk factor for AD with T2D and it also affects the expression level of PI3K protein.However,the polymorphism is not shown to be exclusive in AD patients with T2D.
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Objective To explore the related risk factors and control measures for senium patients with type 2 diabetes and to provide basis for making control and prevention measures.Methods A retrospective case-control study was conducted.548 cases of type 2 diabetes patients in our hospital were selected as case group and other 640 cases of normal people who accepted physical examination in our hospital were selected as control group.Results Exposure rates of smoking,drinking,obesity,hypertension,hypedipidemia and family history in case group were obviously higher than those of control group(P ＜0.05).Conclusion Smoking,drinking,obesity,hypertension,hyperlipidemia and family history were risk factors of type 2 diabetes.Comprehensive intervention measures related to the risk factors,such as maintaining a good way life,were importantto prevent and control type 2 diabetes.
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Objective To investigate possible neural mechanism of anisometropic amblyopia by analysing the whole brain volume changes both in grey matter and white matter using optimized voxel-based morphometry (VBM).Methods Twelve anisometropic amblyopia patients and 12 age,gender and handedness matched healthy volunteers underwent 3-dimensional (3D) fast spoiled gradient echo (FSPGR)sequence scanning on 1.5 Tesla MR system.Raw data was processed and analyzed using statistical parametric mapping (SPM)5.ResultsCompared to healthy controls,the grey matter exhibiting significantly decreased volume in patients included right cuneus,bilateral occipital gyrus,right middle frontal gyrus,left middle temporal gyrus,right superior temporal gyrus,right precuneus,and middle part of right cingulate gyrus ( clusters ＞ 10).The grey matter showing increased volume in patients included right cerebellum,right parahippocampal gyrus,left precentral gyrus,and left superior frontal gyrus (clusters ＞ 10).The white matter volume in bilateral optic radiation and internal capsule,especially right optic radiation,decreased significantly in patient group (clusters ＞ 10 ).No white matter showed significantly increased volume in patient group.ConclusionVBM can be used to investigate the changes of grey matter volume and white matter volume in the whole brain of anisometropic amblyopia children,it provides a method to illustrate the presumed neuro-mechanism from a morphologic point of view.
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Primary cell culture, techniques of gene transfection, gelatin zymography, and Western blot were used to investigate the effect of hypoxia on the secretion of MMP-2 and MMP-9 in pulmonary artery endothelial cells (PAEC) and smooth muscle cells (PASMC), and the role of HIF-1. Our results showed that (1) after exposure to hypoxia for 24 h, the protein content and activity of MMP-2 in the PAEC medium as well as these of MMP-2 and MMP-9 in PASMC medium (P<0.01) decreased significantly in contrast to those in normoxic group (P<0.05); (2) after transfection of wild type EPO3'-enhancer, a HIF-1 decoy, the content and activity of MMP-2 and MMP-9 in hypoxic mediums became higher than those in normoxic group (P<0.01), while transfection of mutant EPO3'-enhancer didn't affect the hypoxia-induced down-regulation. It is concluded that hypoxia could inhibit the secretion and activity of MMP-2 and MMP-9 in PAEC and PASMC, which could be mitigated by the transfection of EPO3'-enhancer and that HIF-1 pathway might contribute to hypoxia-induced down-regulation of MMP-2 and MMP-9.
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Calcium oscillation may regulate gene transcription in a frequency-decoding manner during agonist stimulation,which provides an indicator of transcription level in cells. To determine whether persistent exposure to hypoxia may sensitize or blunt cell response to histamine, the effects of 24 h subacute mild hypoxia on histamine-stimulated calcium oscillation frequency were examined in pulmonary artery endothelial cells (PAECs). The results are: (1) 24 h subacute mild hypoxia significantly increased the histamine-stimulated calcium oscillation frequency in PAECs. The averaged frequency of calcium oscillation in posthypoxic PAECs was significantly higher than that in normoxic ones. (2) NADPH oxidase inhibitor, diphenylene iodonium chloride (DPI, 10 μmol/L), abolished histamine-stimulated calcium oscillations both in normoxic and posthypoxic PAECs. (3) Xanthine oxidase inhibitor, oxypurinol (100 μmol/L), did not affect the calcium oscillation kequency in normoxic PAECs. However, it significantly decreased the elevation of calcium oscillation frequency in posthypoxic PAECs. These results demonstrated that, during pulmonary disease related to persistent hypoxia,PAECs become more sensitive to histamine. During histamine stimulation, NADPH oxidase plays a critical role in generating calcium oscillations, while xanthine oxidase may contribute to, at least in part, the increase of calcium oscillation frequency in posthypoxic PAECs.
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Objective To investigate the relationship between protein phosphatase inhibition, tau hyperphosphorylation and neuronal death seen in Alzheimer disease (AD). Methods Co culture of protein phosphatase inhibitor okadaic acid (OA) and neuroblastoma cells (SH SY5Y), by agarose gel electrophoresis to detect DNA fragmentation, and in situ hybridization by TdT mediated biotin labeled dNTP nick end labeling (TUNEL) to further detect the cell apoptosis. Results Incubation of SY5Y cells with 10 nmol/L OA for 24 or 48 hours led to the appearance of DNA fragmentation and a remarkable increase of positive cells from 2 16%?0 94% to 18 05%?3 57% ( P
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AIM: To study the effect of herbal compound poria prescription (CPP) on proliferation and differentiation in primary rat preadipocytes, and to explore the mechanism of this process. METHODS: Primary cultured rat preadipocyte proliferation was determined by cell counting and MTT spectrophotometry. Cell differentiation was determined by Oil Red O staining, and the expression of PPAR? mRNA was determined by RT-PCR. RESULTS: CPP inhibited the proliferation and differentiation of primary rat preadipocytes in a dose-dependent manner, and it also inhibited the expression of PPAR? mRNA. CONCLUSION: CPP inhibits the proliferation of primary rat preadipocytes and inhibits the preadipocyte differentiation by suppressing the expression of PPAR? mRNA.
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AIM: To investigate the effect of exercise stress on chronic cigarette smoking-induced downregulation of expression of large-conductance calcium-activated potassium channel (BK_(Ca)) and voltage-dependent delayed rectifier potassium channel (Kv1.5) in rat bronchial smooth muscle cells. METHODS: Rats were divided into 3 groups: normal control, smoking control and smoking plus exercise training group. The alteration of airway responsiveness and plasma cortisol level were detected, and potassium channel expression and pathological changes in lung tissue were determined with HE staining, immunohistochemistry, in situ hybridization and Western blot techniques. RESULTS: (1) Cigarette smoking induced an increase in airway responsiveness, smoking plus exercise lead to a decrease in airway responsiveness in contrast to smoking control group; (2) Plasma level of cortisol determined immediately after exercise was higher than that determined before exercise; (3) HE staining showed that there was severe chronic pulmonary inflammatory response in smoking control group, which was slight in the smoking plus exercise group; (4) The protein and mRNA expression of BK_(Ca) in cigarette smoking group were less than that in control group in BSMC, the mRNA expression of BK_(Ca) in exercise group were higher than that in smoking group; (5) The protein and mRNA expression of Kv1.5 in smoking group were less than that in control group in BSMC, and expression of Kv1.5 in exercise group was higher than that in smoking group in bronchioli. CONCLUSION: Proper exercise training can increase the expression of potassium channel BK_(Ca) and Kv1.5, and increase the cortisol secretion, which may contribute to the decreasing of airway hyperresponsiveness induced by cigarette smoking. [
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AIM AND METHODS: Using Ca 2+ -sensitive fluorescent probe Fura-2,we measured the changes of _i in cultured rat pulmonary artery endothelial cells (PAEC) and porcine pulmonary artery smooth muscle cells (PASMC) from normoxic (NC group) or chronic hypoxic group (CH group) when they were exposed to acute hypoxia. RESULTS: The increase in _i in 6th passage of PASMC caused by acute hypoxia in CH group was significantly lower than that in the same passage of NC group (P
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AIM: To explore the effects of 5-HT and electrolytes on the airway remodeling in guinea pigs with bronchial asthma.METHODS: 70 guinea pigs were divided into 7 groups: control group,model group,continued model group,5-HT group,anti-5-HT group,high Mg~(2+) group,low Mg~(2+) group.Remodeling model was established with ovalbumin.RESULTS: ① In model group,5-HT of serum and thickness of airway walls were significantly increased compared with control group(P
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AIM: To investigate the possible role of prostaglandin, NO and potassium channel in the adaptive blunting of hypoxic pulmonary vasoconstriction (HPV) in the high altitude animal (pika). METHODS: The effect of L-NAME, indomethacin and 4-AP on the response of isolated lung strips of pika and Wistar rats instead of pulmonary artery to acute hypoxia were studied. RESULTS: (1) After inhibition of prostaglandins by indomethacin, the percentage increase in hypoxic constriction in lung tissue strip of pikas was greater than that in Wistar rats[(64.7?50.9)% vs (19.7?14.1)%], P
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AIM: To investigate the expression of FIZZ1/RELM? in lung tissue of chronic cigarette smoking rat,and to determine the relationship between airway inflammation and airway hyperresponsiveness.METHODS: Made rat model of chronic cigarette smoking was used.The expression of FIZZ1/RELM? in lung tissue was determined by immuno-histochemistry and in situ hybridization.RESULTS: In control rats,FIZZ1/RELM? protein and mRNA expressions were observed at low levels.In cigarette smoking rats,FIZZ1/RELM? expression increased in all the cells especially in bronchial smooth muscle cells,vascular wall cells and alveolar epithelial cells.CONCLUSION: FIZZ1/RELM? is a secreted peptide specifically expressed in lung.Cigarette smoking induces its upregulation,which possibly contributes to cigarette smoking-induced airway hyperresponsiveness.
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Roles of sympathicus, sensory neuropeptides (SNP), metabolites of cyclooxygenase, metabolites of lipoxygenase, endothelium derived relaxing factor (EDRF), reactive oxygen (ROS) and potassium channels (PC) in the hypoxic pulmonary vasoconstriction (HPV) and hypoxic cerebral vasodilation (HCVD) were studied in intact rats, rabbits and dogs. Results were as follows: during hypoxia, the excitation of sympathicus results in a constriction of both pulmonary and cerebral vessels; SNP, EDRF and the opening of 4-AP sensitive PC caused the dilation of both of them; metabolites of lipoxygenase mediated HPV and HCVD, whereas metabolites of cyclooxygenase were their modulators; hypoxia induced blockade of the ATP sensitive PC mediated HPV, but had no effect on HCVD; reduction of O_2~+ in the lung might potentiate HPV, but had no effect on HCVD. It is suggested that the alteration of lipoxygenase metabolites, ROS and ATP sensitive PC are factors accounting for the difference in response of pulmonary and cerebral vassels to hypoxia.
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AIM: To investigate the effect of compoun d poria prescription (CPP), a Chinese medicine, on weight, blood glucose, blood fa t and microcirculation in nutrition obesity rats and attempt to look for a new a pproach for obesity prevention and cure. METHODS: 30 Wistar rats were divided into normal food raised gro up (group A), high energy food raised group (group B), and high energy food comb ined with CPP raised group (group C). The changes of weight, blood glucose, bloo d lipid and microcirculation were detected, respectively. RESULTS: After CPP treatment in experimental obesity rats, the a v erage weight reduced from (313.00?17.29) g to (217.50?17.50) g (P
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the normal control group (Pthe continued asthma model group (P
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AIM:To investigate the role of potassium channel expression alteration in chronic cigarette smoking-induced increase in pulmonary vascular responsiveness,the effect of chronic cigarette smoking on large-conductance calcium-activated potassium channel(BKCa) and voltage-dependent delayed rectifier potassium channel(Kv1.5) expression in rat pulmonary smooth muscle cells were investigated in vivo.METHODS: HE staining,immuno-histochemistry and in situ hybridization techniques were used.RESULTS:(1) Chronic cigarette smoking downregulates the protein and mRNA expression of BKCa in pulmonary arterial smooth muscles.(2) Chronic cigarette smoking downregulated the protein and mRNA expression of Kv1.5 in pulmonary arterial smooth muscles.(3) In big artery,BKCa decreased more makedly than Kv1.5,but in small artery,both of them decreased equally.CONCLUSION: Chronic cigarette smoking downregulates the levels of BKCa and Kv1.5 in rat pulmonary arterial smooth muscle cells in vivo,which maybe contribute to the mechanism of cigarette smoking-induced increase in pulmonary vascular responsiveness.