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@#Autophagy is a “self-devouring” biological process of the degradation of organelles and proteins by lysosomes in eukaryotic cells. In the past few years, some results revealed that autophagy played an important role in the regulation of vascular calcification. This review summarized the recent studies on autophagy in the process of vascular calcification, and discussed the effects of electrolyte imbalance, matrix vesicle release, oxidative stress, inflammatory reaction of vascular endothelial cells, and lipid metabolism in autophagy. The research progress of β-catenin/AMPK/CREB/Nrf2-ARE/Erα signal transduction pathways in autophagy induction was reviewed.
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Objective To investigate the hemodynamic changes in a tortuous coronary to elucidate the effects of tortuosity on coronary perfusion and wall shear stress (WSS). Methods A single tortuous and non-tortuous patient-specific left anterior descending (LAD) coronary artery cases were selected. Two LAD models with and without coronary tortuosity were reconstructed in Mimics software and then transferred to the ANSYS Fluent software for performing computational fluid dynamics (CFD) simulation. The hemodynamic characteristics of both the LAD models were compared. Results The vessel WSS of the tortuous coronary artery clearly decreased in the bend section where the maximum curvature was larger than 1 mm-1.Such a scenario could led to an inadequate blood supply in the downstream vessels. A low WSS (0-26 Pa) acted on the outer wall of the bend, whereas the inner wall of the bend had a high WSS (>100 Pa). The mean WSS of the non-tortuous and tortuous models was 10.79 Pa and 36.12 Pa, respectively. The overall WSS of the tortuous model was larger compared with that of the non-tortuous model. Conclusions Coronary tortuosity increased the overall WSS, which could delay the progress of coronary atherosclerosis.
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@#Objective To investivate the effects of VocaStim?-Master electrical stimulation and pharyngeal muscles training on sleep breathing parameters, clinical symptoms and cognitive functions in stroke patients with obstructive sleep apnea syndrome (OSAS). Methods From December 1st, 2014 to November 30th, 2017, 50 stroke patients complicated with OSAS were divided into control group (n = 25) and research group (n = 25). All the patients received routine medicine and rehabilitation, while the research group accepted VocaStim?-Master electrical stimulation and pharyngeal muscles training in addition, for four weeks. Their symptoms were observed, and tested with polysomnography (PSG) and Mini-Mental State Examination (MMSE) before and after treatment.Results After treatment, the clinical symptoms improved (P < 0.05), while apnea hypopnea index (AHI) (t > 2.270, P < 0.05)and oxygen desaturation index (t > 3.044, P < 0.01) decreased, and average oxygen saturation (SaO2) and lowest SaO2 increased (t > 3.095, P < 0.01), in the research group, compared with those before treatment and those in the control group (P < 0.05), the scores of MMSE increased (t > 2.859, P < 0.01). There was no significant difference of AHI, averge SaO2, lowest SaO2 and oxygen desaturation index during the period of treatment in the control group (P > 0.05), nor for the score of MMSE.Conclusion VocaStim?-Master electrical stimulation combined with pharyngeal muscles training could effectively ameliorate nocturnal sleep apnea symptom and improve cognitive functions in stroke patients complicated with OSAS.
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OBJECTIVE:To establish the method for the simultaneous determination of clopidogrel (CLO) and its active metabolites (CATM) and inactive metabolites (CCAM),and to conduct pharmacokinetic study. METHODS:The plasma sam-ple had been derivatized by 2-bromine-3′-methoxy acetophenone(MPB),and was precipitated by acetonitrile. Using carbam-azepine as internal standard,UPLC-MS/MS was adopted. The separation was performed on Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of water(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)using a gradient elution program at the flow rate of 0.50 ml/min. The ESI was equipped and quantitative analysis was operated in posi-tive ion and MRM mode. The mass transition ion-pairs were followed as m/z 322.1→211.8(CLO),m/z 504.1→155.0(the alkyl-ation derivatives of CATM,CATMD),m/z 308.3→198.0(CCAM),m/z 273.2→194.3(internal standard). RESULTS:The lin-ear calibration curves for CLO,CATMD and CCAM were obtained in the concentration range of 0.03-20.00 ng/ml,0.30-200.00 ng/ml and 10.00-10 000.00 ng/ml in plasma,respectively;intra-day and inter-day RSD for them were all less than 15%,and relative error(RE)ranged from -3.5% to 5.7%. Main pharmacokinetic parameters of CLO,CATMD and CCAM in 5 healthy volunteers after oral administration of CLO 300 mg were as follows:cmax were(7.89±5.46),(15.58±8.08),(8 023.33± 1 047.39)ng/ml;tmax were(1.25 ± 0.43),(1.25 ± 0.43),(1.67 ± 0.29)h;t1/2 were (2.31 ± 0.61),(0.64 ± 0.08),(6.53 ± 2.55)h;AUC0-t were(17.19±14.59),(21.39±9.58),(30 648.85±8 026.63)ng·h/ml. CONCLUSIONS:The established method is sensi-tive,rapid and convenient,which is suitable for pharmacokinetic study and plasma concentration determination of CLO and its metabolites.
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Objective To investigate induction effect of AGE on oxidative stress and type Ⅰ ,Ⅲcollagen synthesis in rat cardiac fibroblasts and interference effect of RGZ during the course. Methods Incubate rat cardiac fibroblasts with AGE of different concentration ,add RGZ to interfere for 48 h ,and then collect supernatant fluid .Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by SOD kit and MDA kit separately ,and type Ⅰ ,Ⅲ collagen contents were measured by ELISA. Results When incubating cardiac fibroblasts with RGZ and 200 mg/L AGE together for 48 h , with the rise of RGZ concentration(0.1 ,1 and 10 mol/L) ,SOD activity in the supernatant fluid of cultured cardiac fibroblasts gradually increased [(21.564 ± 1.614) ,(22.323 ± 1.260) ,(23.661 ± 1.562) vs (19.320 ± 0.896) nU/ml ,P<0.05 or P<0.01] ,MDA content gradually decreased [(1.325 ± 0.048) ,(1.279 ± 0.032) ,(1.229 ± 0.045 ) vs (1.629 ± 0.043 ) nmol/ml ,P< 0.01 ] and type Ⅰ ,Ⅲ collagen Contents gradually decreased [(79.17 ± 3.25) ,(60.42 ± 3.58) ,(42.71 ± 5.11) vs (85.54 ± 2.28) ng/ml ,P<0.01 ;(37.52 ± 3.43) ,(27.09 ± 4.75) ,(20.81 ± 3.26) vs (40.75 ± 2.70) ng/ml ,P<0.01] as compared with 200 mg/L AGE group. Conclusion AGE can induce oxidative stress in cardiac fibroblasts and increase type Ⅰ ,Ⅲ collagen contents .RGZ can inhibit oxidative stress in cardiac fibroblasts and synthesis and secretion of type Ⅰ ,Ⅲ collagen induced by AGE. This finding indicates that RGZ may play an important role in the prevention of diabetic myocardial fibrosis.
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Clinical internship is a key step for training qualified clinician. This article narrates the measures that the hospital have taken to improve administration of clinical internship and teaching quality on the aspect of clinical intern training, examination and quality control.
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Objective To investigate the effects of rosiglitazone on the proliferation,connective tissue growth factor and Smad expression in cultured cardiac fibroblasts induced by advanced glycosylation end-products (AGEs).Methods After being treated with various amounts of rosiglitazone,the cultured neonatal rat cardiac fibroblasts were incubated with AGEs.The status of cardiac fibroblasts proliferation and cell cycle were detected by 3-(4,5-dimethyhhiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTI) assay and flow cytometry.Furthermore,ELISA technique was applied to identify the level of TGF-β1.The protein expressions of CTGF and Smad in cardiac fibroblasts of neonatal SD rats were detected with Western blotting.Results The exposure of cardiac fibroblasts to AGEs at doses of 0-200 mg/L induced a dose-dependent increase in cell proliferation.At the concentration of rosiglitazooe (0.1,1,and 10 μmol/L),the cell proliferation was reduced compared with 200 mg/L AGEs group by O.823±0.072,0.785±0.060,0.601±0.081 vs 0.981±0.049,respectively (P < 0.05).The increased levels of TGF-β1 in supematants of cultured cardiac fibroblasts stimulated by AGEs were inhibited by rosiglitazone at the concentrations of 0.1,1,10μmol/L by 257.77±9.09,230.29±6.56,200.84±10.26 vs 300.68±8.56,respectively (vs 200 mg/L AGEs,P<0.01).Western blot indicated that pretreatment with rosiglitazone (0.1,1,and 10 μmol/L) inhibited CTGF protein production in a dose-dependent by 0.769±0.108,0.590±0.095,0.534±0.115 vs 1.021±0.113,respectively (vs 200 mg/L AGEs,P<0.01).It was also demonstrated that pretreatment with rosiglitazone (1 and 10 μmol/L) inhibited Smad2 protein production by 0.424±0.059,0.396±O.080 vs 0.572±0.073,respectively (vs 200 mg/L AGEs,P < 0.05 or P < 0.01).Meanwhile pretreatment with rosiglitazone (1 and 10 μmol/L) inhibited Smad4 protein production by 0.580±0.063,0.556±0.051 vs 0.672±0.059,respectively (vs 200 mg/L AGEs,P < 0.05 or P < 0.01).Conclusions The findings suggest that AGEs promote the proliferation of cardiac fibroblasts and stimulate the protein production of Smad and CTGF of cardiac fibroblasts.Rosiglitazone inhibits the above reaction.These results indicate that CTGF/Smad pathway may play an important role in the protective effect of rosiglitazone on myocardial fibrosis.
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Objective To explore the effect of advanced glycosylation end products (AGEs) on expression of connective tissue growth factor (CTGF) in cultured rat vascular smooth muscle cells (VSMCs) and the mechanism of accelerated atherosclerosis in diabetes. Methods VSMCs were isolated and cultured from the thoracic aorta of rat. Reverse transcription polymerase chain reaction (RT-PCR) and Western immunoblot analysis were used to detect the expression level of CTGF mRNA and protein. Results The expression of CTGF mRNA and protein were increased by AGE-BSA in the time- and dose-dependent manners(P<0.05). Conclusions AGEs may increase the expression activity of CTGF in cultured vascular smooth muscle cells.
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The effect of rosiglitazone and advanced glycation end products (AGEs) on the expression of fractalkine in cultured human renal mesangial cells (HRMC) were investigated. Rosiglitazone inhibits the upregulation of fractalkine induced by AGEs in HRMC.
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Objective To observe the effect of advanced glycosylation end products(AGEs) on gene expression of connective tissue growth factor(CTGF) in NIH Swiss mouse embryo fibroblasts(NIH/3T3),and to assess the intervention actions of aminoguanidine(AG) and puerarin(Pue) on CTGF mRNA expression in NIH/3T3.Methods AGEs were synthesized by coincubation of BSA with glucose.The AGEs content was measured by fluorescence spectroscopy.NIH/3T3 cells were treated with AGEs(prepared with 20,50,80 mmol?L-1 glucose) for 24 h.The NIH/3T3 cells were treated with AGEs(prepared with 50 mmol?L-1 glucose) for 0,6,12,24 and 48 h.The intervention actions of AG and Pue with different concentration(0.25,0.5,1.0 and 1.5 g?L-1) were evaluated.The CTGF mRNA expression in NIH/3T3 was determined by RT-PCR.Results Compared with BSA control,the CTGF mRNA expression levels in NIH/3T3 were increased by treatment with AGEs(prepared with 20,50,80 mmol?L-1 glucose) for 24 h(P
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An intensive practice scheme,integrating clinical practicing education with continuing medieal education after graduation was introduced to Provide a new mode of teaching activities and management of clinical practice.
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<p><b>OBJECTIVE</b>To determine whether advanced glycosylation end products modified bovine serum albumin (AGEs-BSA) affects endothelial cell lateral junction protein, platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the presence or absence of inflammatory mediators.</p><p><b>METHODS</b>Cultured human umbilical vein endothelial cells (HUVECs) were exposed to AGEs-BSA for 6, 12, 24, and 36 hours, and exposed to AGEs-BSA glycosylated with different concentrations of glucose, tumor necrosis factor-alpha (TNF-alpha), interferon (IFN-gamma), TNF-alpha + IFN-gamma and AGEs-BSA + TNF-alpha for 24 hours, respectively. Expression of PECAM-1 mRNA was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) with beta-actin as an internal standard, and sequencing of RT-PCR products was performed to confirm the specificity of amplification for PECAM-1 gene. The endothelial cell surface expression of PECAM-1 was determined by flow cytometry (FCM).</p><p><b>RESULTS</b>There were no significant changes in the expression of PECAM-1 mRNA and protein when the cells were exposed to AGEs-BSA with different concentrations or periods (P > 0.05). However, PECAM-1 expression was reduced in the cells treated with TNF-alpha, IFN-gamma, TNF-alpha + IFN-gamma and AGEs-BSA + TNF-alpha. The level of PECAM-1 treated with AGEs-BSA + TNF-alpha was lower than that of TNF-alpha treated alone (P < 0.01).</p><p><b>CONCLUSIONS</b>AGEs-BSA had no effect on the expression of PECAM-1 mRNA and protein in cultured HUVEC. With the presence of inflammatory mediator TNF-alpha, AGEs-BSA decreased the level of PECAM-1, which might reduce the adhesion interaction between adjacent endothelial cells, enhance the permeability of endothelial cells, and might be implicated in the endothelial dysfunction and pathogenesis of atherosclerosis in patients with diabetes mellitus. The significance of this phenomenon in intracellular signal transduction remains to be determined.</p>
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Humans , Cells, Cultured , Endothelial Cells , Chemistry , Glycation End Products, Advanced , Pharmacology , Interferon-gamma , Pharmacology , Platelet Endothelial Cell Adhesion Molecule-1 , Serum Albumin, Bovine , Pharmacology , Tumor Necrosis Factor-alpha , Pharmacology , Umbilical VeinsABSTRACT
AIM: To observe the effect of ?-glucosindase inhibitor, acarbose on the aortic collagen nonenzymatic glycosylation in streptozotocin-induced diabetic rats . METHODS: The treated group (DM+A) was given acarbose (1 mg?kg -1 ). The aortic collagen and its AGEs concentration were measured at the scheduled periods (1, 3 and 6 months ). RESULTS: During the observed period , the aortic collagen and its AGEs concentration were higher than that of control group in a time-dependent manner (P
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The formation of advanced glycosylation end products (AGEs) is enhanced in diabetes mellitus, closely associated with diabetic vascular complication. In this review, biochemical properties and structures of AGEs,AGEs receptors and binding proteins ,pathogenic properties of AGEs,deposition and turnover of AGEs, inhibitors of AGEs were summarized.
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There is overwhelming evidence for an involvement of reactive oxygen species(ROS) in the pathogenesis of atherosclerosis(AS) in diabetes mellitus(DM). For many years, knowledge on the contribution to diabetic complications and vascular disease induced by advanced glycation end-products(AGEs)has been rising. During the development of atherosclerosis, AGEs and ROS might have interaction. In this article, we provided four angles of view to discuss the role of ROS in the pathogenesis of atherosclerosis: the chemistry of ROS, the effect of vascular targets of ROS on activity of AGEs, the role of ROS in the pathogenesis of atherogenesis by AGEs, the same effect of ROS and AGEs-transcriptional regulation. [
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The changes of[Ca~(2+)]and metabolism of lipid in human monocyte-macrophages as inter- acted with glycosylated LDL(glc-LDL)were observed.The intracellular[Ca~(2+)]was higher than that of LDL(P
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AIM: To investigate the effect of L-arginine(L-arg) on the production of collagens of human mesangial cells. METHODS: Radioimmunoassay, hydroxyproline colorimetric assay and reverse transcription polymerase chain reaction (RT-PCR) were used to determine procollagen Ⅲ, total collagen level in the supernatant and expression of collagen Ⅳ mRNA in human mesangial cells. RESULTS: L-arg significantly inhibited the production of procollagenⅢ, total collagen in the supernatants ( P
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This study was designed to investigate the effects of calcium antagonists and glucosylated LDL on intracellular lipid metabolism . The human serum LDL was isolated by density gradient ultracentri-fugation and glucosylated by incubation with glucose. The content of intracellular cholsterol was determined by enzymatic method which is simple, convenient and satisfactory. It was found that the contents of cholesterol in cultured human fibroblasts incubated with verapamil and(or)glucosylated LDL were higher than those incubat- ed with control LDL or without verapamil. The results suggested that calcium antagonists and glucosylation of LDL might affect in-tracellular lipid metabolism and play a role in atherosclerosis.
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In order to investigate the action of calcium antagonists on metabolism of intracellular macromolecules, The authors observed the effects of verapamil on the incor-poration of 〔 3H 〕 TdR, 〔 3H 〕 UR and 〔 3H 〕 Leu into human fibroblasts. The inhibitory effects on DNA and RNA synthesis were concentration dependent, ID50 was l2.3mg/L and 22mg/L, respectively. The inhibitory effect on the synthesis of protein was weak.
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Objective To study the effects of puerarin on advanced glycation end products (AGEs) and expression of monocyte chemoattractant protein-1 (MCP-1) in diabetic rats. Methods The rats were randomly divided into normal control rats (CON rats), diabetic rats (DM rats), diabetic rats treated with aminoguanidine (AG rats), and diabetic rats treated with puerarin (PU rats). The diabetic rat model was induced by streptozotocin. The serum levels of AGEs and MCP-1 were quantified by fluorescence spectroscopy and ELISA respectively. Tissue sections with PAS staining and electronic microscopy were used for observation of the pathologic changes in renal tissues. Immunohistochemistry was applied to detect the expression of MCP-1 protein in renal cortex. Results Serum levels of AGEs and MCP-1 in DM rats were higher than those in PU rats and AG rats (both P