RESUMEN
Objective To observe the effect of Dangua Recipe (DR) on adiponectin receptor 2 (AdipoR2) expression in liver of apolipoprotein E knockout (ApoE⻹â») diabetic mice. Methods Eight- week-old ApoE⻹⻠mice were randomly divided into the model control group, the DR group, the pioglitazone group, and the combined treatment group. Besides, a C57 group was set up consisting of same age C57BL/ 6J mice. Streptozotocin (STZ) was injected to ApoE⻹⻠mice in the four groups to induce diabetic model, and they were intervened by corresponding drugs. After 12 weeks the effect of DF on glucose-lipid metabolism was observed. mRNA and protein expressions of AdipoR2 in liver were detected. Histomorphological changes of the liver were observed by hematoxylineosin ( HE) staining, red Ο fat dyeing, and Masson staining, respectively. Results Contents of fasting blood glucose (FBG) , total cholesterol (TC) , and low-density lipoprotein cholesterol (LDL-C) were reduced more significantly in the DR group than in the model group. DR could promote liver expression of AdipoR2 mRNA and protein expressions in ApoE⻹⻠mice, which was significantly higher than that of the model group (P <0. 01) , and better than that of pioglitazone (P <0. 05, P <0. 01). DR could improve ectopic fat deposition and fibrosis of liver cells in diabet- ic ApoE⻹⻠mice significantly, which was better than that of the pioglitazone group and the combined treatment group. Conclusion DR could significantly improve liver lipid metabolism , and reduce liver fat deposition and fibrosis, which might possibly be associated with promoting AdipoR2 expression in liver.
Asunto(s)
Apolipoproteínas E , Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Receptores de Adiponectina , Animales , Apolipoproteínas E/genética , Diabetes Mellitus Experimental/metabolismo , Medicamentos Herbarios Chinos/farmacología , Hígado , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Adiponectina/efectos de los fármacos , Receptores de Adiponectina/metabolismoRESUMEN
OBJECTIVE: To study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy. METHODS: Diabetic model was prepared by peritoneally injecting streptozotocin (STZ) to Apo E(-/-) mouse. Totally 32 modeled mice were stratified by body weight, and then divided into 4 groups referring to blood glucose levels from low to high by random digit table, i.e., the model group (MOD, fed with sterile water, at the daily dose of 15 mL/kg), the DGR group (fed with DGR at the daily dose of 15 mL/kg), the combination group (COM, fed with DGR at the daily dose of 15 mL/kg and pioglitazone at the daily dose of 4.3 mg/kg), and the pioglitazone group (PIO, at the daily dose of 4.3 mg/kg), 8 in each group. Another 8 normal glucose C57 mouse of the same age and strain were recruited as the control group. All interventions lasted for 12 weeks by gastrogavage. The fasting blood glucose (FBG), body weight, food intake, water intake, skin temperature, the length of tail, and the degree of fatty liver were monitored. The hemoglobin A1c (HbA1c), total cholesterol (TC), and LDL-C were determined. Endothelin-1 (ET-1) was determined by radioimmunoassay. Nitrogen monoxidum (NO) was determined by nitrate reductase. The kidney tissue VCAM-1 level was analyzed with ELISA. The expression of VCAM-1 mRNA in the kidney tissue was detected with real time quantitative PCR. RESULTS: Compared with the control group, the body weight and food intake decreased, water intake increased in all the other model groups (P < 0.05). Besides, the curve of blood glucose was higher in all the other model groups than in the control group (P < 0.01). Compared with the model group, the body weight increased; levels of HbAlc, TC, LDL-C, ET-1, and VCAM-1 were significantly lower; and skin temperature was higher in the DGR group (P < 0.05, P < 0.01). Compared with the PIO group, body weight, the increment of body weight, FBG, TC, and LDL-C were lower (P < 0.05, P < 0.01); food intake and water intake increased more and the tail length was longer in the DRG group (P < 0.01). There was no statistical difference in the level of NO among groups. The degree of fatty liver in the model group was significantly severer than that in the control group (P < 0.05). It was obviously alleviated in the DGR group (P < 0.05) when compared with the model group and the PIO group (P < 0.05, P < 0.01). But it was severer in the PIO group than in the model group (P < 0.01). The degree of fatty liver in the combination group ranged between that of the DGR group and the PIO group (P < 0.05). The level of VCAM-1 mRNA expression was significantly lower in the DGR group than in the model group, the PIO group, and the combination group (P < 0.05). CONCLUSIONS: DGR had effect in lowering blood glucose and blood lipids, and fighting against fatty liver of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis. DGR played an effective role in preventing and treating DM with angiopathy by comprehensively regulating glycolipid metabolism and promoting the vascular function.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Animales , Apolipoproteínas E/genética , Glucemia/metabolismo , Diabetes Mellitus Experimental/sangre , Angiopatías Diabéticas/tratamiento farmacológico , Lípidos/sangre , Masculino , Ratones , Ratones Noqueados , Pioglitazona , ARN Mensajero/genética , Distribución Aleatoria , Tiazolidinedionas/farmacología , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
Background: There is no doubt that both Hashimoto thyroiditis and Graves' disease are autoimmune thyroid diseases (AITDs), but the relationship between anti-nuclear antibody (ANA) and AITDs is poorly studied. The association between thyroid autoantibody levels and ANA positivity was evaluated to assess the role of ANA in AITDs. Methods: We conducted an analysis using data from 1,149,893 patients registered at our hospital and 53,021 patients registered in the National Health and Nutrition Examination Survey databases. We focused on patients with data for thyroid peroxidase antibody (TPOAb)/ANA, TPOAb/immunoglobulin G (IgG), thyroid-stimulating hormone (TSH) receptor antibody (TRAb)/ANA, TRAb/IgG, TSH/ANA, or TSH/IgG. Results: ANA positivity rates were 12.88% and 21.22% in TPOAb/ANA and TSH/ANA patients, respectively. In TPOAb/IgG and TSH/IgG data, high IgG levels (≥15 g/L) were detected in 2.23% and 4.06% of patients, respectively. There were significant differences in ANA positivity rates and high IgG proportions among patients with different TPOAb and TSH levels. TPOAb level was correlated with ANA positivity rate and high IgG proportion, and TSH level was correlated with ANA positivity rate. Regression analysis showed positive correlations between TPOAb levels and ANA positivity risk or high IgG risk, TSH levels and high IgG risk, and elevated TSH and ANA positivity risk. Of patients with TRAb/ANA data, 35.99% were ANA-positive, and 13.93% had TRAb levels ≥1.75IU/L; 18.96% of patients with TRAb/IgG data had high IgG levels, and 16.51% had TRAb levels ≥1.75IU/L. ANA positivity rate and high IgG proportion were not significantly different among different TRAb levels. TRAb levels, ANA positivity risk and high IgG risk were not correlated. Conclusion: ANA positivity and high IgG are related to Hashimoto thyroiditis but not Graves' disease, which implies distinct pathophysiological mechanisms underlying the AITDs.
Asunto(s)
Enfermedad de Graves , Enfermedad de Hashimoto , Humanos , Encuestas Nutricionales , Autoanticuerpos , Enfermedad de Graves/diagnóstico , Receptores de Tirotropina , Inmunoglobulina G , TirotropinaRESUMEN
OBJECTIVE: To explore the effects of Dangua Recipe (DGR) on glycolipid metabolism, serum reactive oxygen species (ROS) level, nuclear factor kappa B (NF-kappaB) positive expression and its mRNA expression level in the thoracic aorta of diabetic rats with atherosclerosis, thus revealing its partial mechanisms for intervening chronic diabetic complications. METHODS: Recruited 40 Goto-Kakisaki (GK) Wistar rats were fed with high fat forage containing metabolic inhibition Propylthiouracil, and peritoneally injected with endothelial NOS inhibitor N-nitro-L-arginine methyl ester to establish a high fat diabetes model with atherosclerosis. The modeled GK rats were stratified by body weight, and then, by blood glucose level from high to low, randomly divided into the DGR group (at the daily dose of 8 mL/kg), the metformin group (MET, at the daily dose of 150 mg/kg), the simvastatin group (SIM, at the daily dose of 2 mg/kg), and the model group (MOD, fed with pure water, at the daily dose of 8 mL/kg) according to the random number table, 10 in each group. Another 10 Wistar rats of the same ages and comparable body weight level were recruited as the normal control group. All the interventions lasted for 24 weeks by gastrogavage. The fasting blood glucose (FBG) and body weight were monitored. The HbA1c, TC, LDL-C, HDL-C, TG, serum ROS were determined. The aortic NF-kappaB level was analyzed with immunohistochemical assay. The expression of NF-kappaB (P65) mRNA in the aorta was detected with Real-time PCR. RESULTS: The body weight in the normal control group was eventually heavier than others (P < 0.01). There was no difference among the four groups of GK modeled rats (P > 0.05). The FBG in the four GK modeled groups were higher than that in the normal control group (P < 0.01, P < 0.05). There was no statistical difference in the blood glucose level at the first visit and at the baseline among the GK modeled groups (P > 0.05). The last FBG level was obviously lower in the MET and DGR groups than in the MOD group (P < 0.01) and the SIM group (P < 0.05). Twenty-four weeks after intervention, the level of FBG, HbA1c, TC, LDL-C, HDL-C, and NF-kappaB positive expression rate of the thoracic aorta of the four groups of GK modeled rats, and NF-kappaB mRNA expression in the thoracic aorta in the MOD group, the MET group, and the DGR group were significantly higher than those in the normal control group (P < 0.01, P < 0.05). The TG level, serum ROS in the MET, DGR, and SIM groups, and the NF-kappaB mRNA expression level in the thoracic aorta in the SIM group were significantly lower than those in the normal control group (P < 0.01, P < 0.05). The levels of FBG, TC, LDL-C, serum ROS, NF-kappaB mRNA expression level in the thoracic aorta in three drug intervention groups, and NF-kappaB positive expression rate in the DGR and MET groups, and the levels of HbA1c, TG in the DGR group were significantly lower than those in the MOD group (P < 0.01, P < 0.05). The level of FBG in the MET and DGR groups were lower than that in the SIM group (P < 0.05). The level of NF-kappaB mRNA expression in the thoracic aorta of the SIM and DGR groups, and the levels of TC and LDL-C in the DGR group were significantly lower than those in the MET group (P < 0.01). CONCLUSION: DGR played a role in preventing and treating chronic diabetic complications by comprehensively regulating blood glucose and serum lipids, as well as down-regulating oxidative stress.
Asunto(s)
Aterosclerosis/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Metabolismo de los Lípidos , Estrés Oxidativo , Fitoterapia , Animales , Aorta Torácica/metabolismo , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Glucemia/análisis , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/metabolismo , Modelos Animales de Enfermedad , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/sangreRESUMEN
OBJECTIVE: To explore the mechanisms of Dangua Recipe (DGR) in improving glycolipid metabolism based on transcriptomics. METHODS: Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table, including a conventional diet group (Group A), a DGR group (Group B, high-calorie diet + 20.5 g DGR), and a high-calorie fodder model group (Group C). After 12 weeks of intervention, the liver tissue of rats was taken. Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy, and then gene or protein validation of liver tissue were performed. Nicotinamide phosphoribosyl transferase (Nampt) and phosphoenolpyruvate carboxykinase (PEPCK) proteins in liver tissues were detected by enzyme linked immunosorbent assay, fatty acid synthase (FASN) protein was detected by Western blot, and fatty acid binding protein 5 (FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction. Furthermore, the functional verification was performed on the diabetic model rats by Nampt blocker (GEN-617) injected in vivo. Hemoglobin A1c (HbA1c), plasma total cholesterol and triglycerides were detected. RESULTS: Totally, 257 differential-dominant genes of Group A vs. Group C and 392 differential-dominant genes of Group B vs. Group C were found. Moreover, 11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs. Group C and Group C vs. Group B were confirmed. The liver tissue target validation showed that Nampt, FASN, PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome. The in vivo functional tests showed that GEN-617 increased body weight, HbA1c, triglyceride and total cholesterol levels in the diabetic rats (P<;0.05 or P<;0.01); while all the above-mentioned levels (except triglyceride) were decreased significantly by GEN-617 combined with DGR intervention (P<;0.05 or P<;0.01). CONCLUSION: Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.
Asunto(s)
Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Enfermedades Metabólicas , Animales , Glucolípidos , Hígado , Ratas , Ratas Sprague-Dawley , Transcriptoma/genéticaRESUMEN
Traditional glucose-lowering chemical agents, including various types of insulin and insulin secretagogues, insulin sensitizers, gliptins, etc., are based on diabetic pathogenesis of insulin resistance (IR) and islet insufficiency. Numerous evidence-based medical studies have shown that these traditional hypoglycemic chemical agents do not provide cardiovascular benefit to patients with type 2 diabetes mellitus (T2DM) and may even increase the risk of all-cause mortality. Based on research evidence published to date, these studies show that overload of energy could increase the incidence and prevalence of T2DM, and reduction in the heat load can significantly reduce the incidence of T2DM. Therefore, the essence of T2DM is heat overload, meaning heat overload is the etiology of obese T2DM. At the same time, results of numerous studies show that heat overloading is the cause of IR. IR and islet dysfunction are protective factors in intervening with heat overload. These drugs, which are based on the mechanisms of IR and islet insufficiency, increase caloric reserve and cause or worsen obesity, which is equivalent to exacerbating the basic etiology and the cardiovascular risk factor of T2DM. Thus, a reasonable strategy for prevention and treatment of obese T2DM appears to promote the negative balance of calories and the elimination of caloric reserves. Chinese herbal medicines can promote negative balance of heat in many aspects, which can bring new hope for prevention and treatment of T2DM.
Asunto(s)
Restricción Calórica/métodos , Diabetes Mellitus Tipo 2/terapia , Medicamentos Herbarios Chinos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Obesidad/terapia , HumanosRESUMEN
The encapsulation or coating of conductive materials is an effective strategy to increase the electrochemical ion-storage performance of some promising electrode materials such as transition metal oxides and sulfides, which are low-cost and have high capacity, but their practical applications are hindered by their intrinsically low conductivity and large volume changes during cycling; however, to date, the effect of the thickness of conductive layers on the ion-storage performance has been rarely studied. In this study, taking nanoscale polypyrrole (PPY)-coated FeS2 as an example, the effect of the critical thickness of the conductive PPY coating on the lithium-ion storage performance of (PPY)-coated FeS2 as a cathode of rechargeable lithium-ion batteries (LIBs) was investigated. Via a facile vapor-phase polymerization method, uniform PPY coatings with the thickness of 1-18 nm on microsized FeS2 particles were prepared. It was found that the critical thickness of PPY was 5 nm, at which the PPY-coated FeS2 cathode exhibited remarkablely superior high-rate capability (808, 583, 543, 511, and 489 mA h g-1 at 0.1, 1, 2, 5 and 10 A g-1, respectively) and long-term stability (504 mA h g-1 at 1.0 A g-1 after 500 cycles) as compared to those with other coating thicknesses owing to the acheivement of optimal electrical conductivity and ion diffusion efficiency. Thus, this study provides an insight into the critical thickess of a surface-functionalized coating of active materials and opens a new avenue for the futher enhancement of the performance of energy storage deivces.
RESUMEN
Hyperglycemia significantly increases the risk of cardiovascular disease (CVD) in diabetics. However, it has been shown by a series of large scale international studies that intensive lowering of blood glucose levels not only has very limited benefits against cardiovascular problems in patients, but may even be harmful to patients at a high risk for CVD and/or poor long-term control of blood glucose levels. Therefore, Western medicine is faced with a paradox. One way to solve this may be administration of Chinese herbal medicines that not only regulate blood glucose, blood fat levels and blood pressure, but also act on multiple targets. These medicines can eliminate cytotoxicity of high glucose through anti-inflammatory and anti-oxidant methods, regulation of cytokines and multiple signaling molecules, and maintenance of cell vitality and the cell cycle, etc. This allows hyperglycemic conditions to exist in a healthy manner, which is called "harmless hyperglycemia" Furthermore, these cardiovascular benefits go beyond lowering blood glucose levels. The mechanisms of action not only avoid cardiovascular injury caused by intensive lowering of blood glucose levels, but also decrease the cardiovascular dangers posed by hyperglycemia.
Asunto(s)
Glucemia/análisis , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus/sangre , Medicamentos Herbarios Chinos/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/etiologíaRESUMEN
OBJECTIVE: To investigate the effect of Dan-gua Fang on adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism. METHODS: Forty 13-week-old diabetic Goto-Kakizaki (GK) rats were randomly divided into model, Dan-gua Fang, metformin and simvastatin groups (n=10 for each), and fed high-fat diet ad libitum. Ten Wistar rats were used as normal group and fed normal diet. After 24 weeks, liver expression of AMPKα mRNA was assessed by real-time PCR. AMPKα and phospho-AMPKα protein expression in liver was evaluated by Western blot. Liver histomorphology was carried out after hematoxylin-eosin staining, and blood glucose (BG), glycosylated hemoglobin A1c (HbA1c), food intake and body weight recorded. RESULTS: Similar AMPKα mRNA levels were found in the Dan-gua Fang group and normal group, slightly higher than the values obtained for the remaining groups (P<0.05). AMPKα protein expression in the Dan-gua Fang group animals was similar to other diabetic rats, whereas phospho-AMPKα (Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group (P<0.05), respectively. However, phosphor-AMPKα/AMPKα ratios were similar in all groups. Dan-gua Fang reduced fasting blood glucose with similar strength to metformin, and was superior in reducing cholesterol, triglycerides, high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin. Dan-gua Fang decreases plasma alanine aminotransferase (ALT) significantly. CONCLUSION: Dan-gua Fang, while treating phlegm-stasis, could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet, and effectively protect liver histomorphology and function. This may be partly explained by increased AMPK expression in liver. Therefore, Dan-gua Fang might be an ideal drug for comprehensive intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/enzimología , Medicamentos Herbarios Chinos/uso terapéutico , Glucolípidos/metabolismo , Hígado/enzimología , Proteínas Quinasas Activadas por AMP/genética , Animales , Glucemia/metabolismo , Peso Corporal , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/metabolismo , Conducta Alimentaria , Hígado/patología , Masculino , Fosforilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de TiempoRESUMEN
The Duhuo Jisheng Decoction (DHJSD), a traditional Chinese medicine (TCM), has been widely used to treat osteoarthritis (OA). However, the mechanisms of action of the DHJSD have not been clearly elucidated. In the present study, the compounds in the DHJSD were characterized by three computational methods; the ligand clustering, chemical space distribution and network construction and analysis methods. The compounds that formed the medical composition of the DHJSD were divided into 10 clusters and possessed a broad diversity in chemical space distribution. The compounds also had the same coverage of chemical space as the OA drug/druglike compounds from DrugBank. In addition, multiple active compounds were identified as able to target multiple proteins in the drugtarget association networks (DT networks). A certain number of key compounds in the DT networks have been previously reported in the literature. The present study also constructed drugdrug association networks (DD networks) and classified the DHJSD compounds into five clusters. The clusters represented multiple diverse combinations binding to the OA targets. These results suggested that the DHJSD had drug and leadlike compounds with potential synergy and polypharmacology against OA.
Asunto(s)
Osteoartritis/metabolismo , Análisis por Conglomerados , Bases de Datos Factuales , Interacciones Farmacológicas , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Medicina Tradicional China , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Programas InformáticosRESUMEN
The herb pair comprising Salvia miltiorrhiza (SM) and Panax notoginseng (PN) has been used as a classical formula for cardiovascular diseases (CVDs) in China and in western countries. However, the pharmacology of SM and PN in this herb pair has not been fully elucidated. The aim of this study was to compare the mechanisms of SM and PN at the molecular level for the treatment of CVDs. We used a systems pharmacology approach, integrating ligand clustering, chemical space, docking simulation and network analysis, to investigate these two herbal medicines. The compounds in SM were attached to clusters 2, 3, 5, 6, 8 and 9, while the compounds in PN were attached to clusters 1, 2, 4, 5, 6, 7, 8 and 10. The distributions of chemical space between the compounds from SM and PN were discrete, with the existence of small portions of overlap, and the majority of the compounds did not violate 'Lipinski's rule of five'. Docking indicated that the average number of targets correlated with each compound in SM and PN were 5.0 and 3.6, respectively. The minority nodes in the SM and PN drug-target networks possessed common values of betweenness centrality, closeness centrality, topological coefficients and shortest path length. Furthermore, network analyses revealed that SM and PN exerted different modes of action between compounds and targets. These results suggest that the method of computational pharmacology is able to intuitively trace out the similarities and differences of two herbs and their interaction with targets from the molecular level, and that the combination of two herbs may extend their activities in different potential multidrug combination therapies for CVDs.
RESUMEN
OBJECTIVE: To study the toxicity features of high glucose on the endothelial cell cycle and the influence of Dan Gua-Fang, a Chinese herbal compound prescription, on the reproductive cycle of vascular endothelial cells cultivated under a high glucose condition; to reveal the partial mechanisms of Dan Gua-Fang in the prevention and treatment of endothelial injury caused by hyperglycemia in diabetes mellitus (DM); and offer a reference for dealing with the vascular complications of DM patients with long-term high blood glucose. METHODS: Based on the previous 3-(4,5)-dimethylthiahiazo (z-y1)-3-5-diphenytetrazoliumromide (MTT) experiment, under different medium concentrations of glucose and Dangua liquor, the endothelial cells of vein-304 (ECV-304) were divided into 6 groups as follows: standard culture group (Group A, 5.56 mmol/L glucose); 1/300 herb-standard group (Group B); high glucose culture group (Group C, 16.67 mmol/L glucose); 1/150 herb-high glucose group (Group D); 1/300 herb-high glucose group (Group E); and 1/600 herb-high glucose group (Group F). The cell cycle was assayed using flow cytometry after cells were cultivated for 36, 72 and 108 h, respectively. RESULTS: (1) The percentage of cells in the G0/G1 phase was significantly increased in Group C compared with that in Group A (P<0.05), while the percentage of S-phase (S%) cells in Group C was significantly reduced compared with Group A (P<0.05); the latter difference was dynamically related to the length of growing time of the endothelial cells in a high glucose environment. (2) The S% cells in Group A was decreased by 30.25% (from 40.23% to 28.06%) from 36 h to 72 h, and 12.33% (from 28.06% to 24.60%) from 72 h to 108 h; while in Group C, the corresponding decreases were 23.05% and 21.87%, respectively. The difference of S% cells between the two groups reached statistical significance at 108 h (P<0.05). (3) The percentage difference of cells in the G2/M phase between Group C and Group A was statistically significant at 72 h (P<0.01). (4) 1/300 Dan Gua-Fang completely reversed the harmful effect caused by 16.67 mmol/L high glucose on the cell cycle; moreover it did not disturb the cell cycle when the cell was cultivated in a glucose concentration of 5.56 mmol/L. CONCLUSIONS: High glucose produces an independent impact on the cell cycle. Persistent blocking of the cell cycle and its arrest at the G0/G1 phase are toxic effects of high glucose on the endothelial cell cycle. The corresponding variation of the arrest appears in the S phase. 1/300 Dan Gua-Fang completely eliminates the blockage of high glucose on the endothelial cell cycle.
Asunto(s)
Ciclo Celular/efectos de los fármacos , Citoprotección/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Células Endoteliales/efectos de los fármacos , Glucosa/efectos adversos , Ciclo Celular/fisiología , Células Cultivadas , Medios de Cultivo/farmacología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Células Endoteliales/fisiología , Citometría de Flujo , HumanosRESUMEN
Chemical investigation of Semen Persicae has led to the isolation of decane (1), triolein (2), nonacosanoic acid (3), oleic acid ethyl ester (4), palmitic acid (5), oleic acid (6) and 15,16-dihydroxy-9Z,12Z-octadecadienoic acid 2,3-dihydroxypropyl ester (7). Amongst these, compound 7 is a new lipid. Their structures were elucidated by chemical and extensive spectral analysis. Their anticoagulative activities were also evaluated in vitro, which showed that petroleum ether extract and compounds 5-6 could significantly prolong thrombin time while methanol extract could obviously inhibit platelet aggregation.
Asunto(s)
Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Fibrinolíticos/aislamiento & purificación , Fibrinolíticos/farmacología , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Prunus/química , Semillas/química , Alcanos/aislamiento & purificación , Animales , Plaquetas/efectos de los fármacos , Medicamentos Herbarios Chinos/análisis , Ácidos Grasos Insaturados/aislamiento & purificación , Fibrinolíticos/análisis , Masculino , Estructura Molecular , Nefelometría y Turbidimetría , Ácidos Oléicos/aislamiento & purificación , Ácido Palmítico/aislamiento & purificación , Inhibidores de Agregación Plaquetaria/análisis , Conejos , Tiempo de Trombina , Trioleína/aislamiento & purificaciónRESUMEN
OBJECTIVE: To evaluate the impact of surface modification on the DNA-binding ability of nano-hydroxyapatite (nHA). METHODS: Chemical co-precipitation-hydrothermal synthesis was utilized to prepare the nHA particles, and polyethylenimine (PEI) was used for surface modification of the nHA. Transmission electron microscopic (TEM) observation and zeta potential detection of the nHA were carried out before and after surface modification. The abilities of the nanoparticles, at different pH values and different concentrations, for DNA-binding and DNA protection against nuclease digestion were assessed before and after surface modification by electrophoresis. RESULTS: TEM observation showed a short rod-like morphology of PEI-modified nHA with uniform particle size and good dispersion; the nHA without the modification tended to aggregate with poor dispersion. With a positive zeta potential, the PEI-modified nHA showed an obviously enhanced ability of DNA binding at different pH values and concentrations, with strong capacity to protect the DNA against Dnase I digestion. At the concentration of 250 µg/ml and a pH value of 7.0, the nHA-PEI showed an optimal efficiency of DNA-binding and DNA protection. CONCLUSION: nHA with surface modification by PEI can serve as an effective vector for DNA binding and transfer.