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The main purpose of this paper is to study the effect of propylene glycol alginate sodium sulfite nanoparticles on myocardial injury in diabetic rats through Sirt1/HIF-1 α signal pathway. The effects of different doses of propylene glycol alginate sodium sulfite nanoparticles on the content of malondialdehyde, creatine kinase, nitric oxide, the activity of superoxide dismutase, lactate dehydrogenase and nitric oxide synthetase in the myocardial tissue of diabetic rats observed. The function indexes of HIF-1 α mitochondria and measured the expression of Sirt1/HIF-1 α pathway. The results show that compare with the diabetic model group, the blood glucose level of the rats in the propylene glycol alginate sodium sulfite nanoparticles treatment group was slightly low. The serum LDH, CK and MDA contents were significantly low, and the activity of SOD in the myocardium in the propylene glycol alginate sodium sulfite nanoparticles treatment group was significantly higher than that in the diabetic model group in the treatment group. The activity of NOS and the content of MDA and no were lower than that in the diabetic rats, the expression of Sirt1 and HIF-1α in myocardial tissue was increased. It suggested that propylene glycol alginate sodium sulfite nanoparticles alleviate myocardial damage in diabetic rats by regulating Sirt1/HIF-1α signal pathway, improving mitochondrial function and inhibiting oxidative stress.
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Diabetes Mellitus Experimental , Nanopartículas , Alginatos , Animales , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoxia , Miocardio , RatasRESUMEN
The present study aimed to investigate the protective effects and mechanisms of Didymin from Mentha spicata on non-alcoholic fatty liver disease (NAFLD) induced by dexamethasone and high-fat diet (DEX/HFD) in C57BL/6J mice. Briefly, mice were acclimated for 5 days and then subjected to DEX/HFD from days 5 to 28; meanwhile, the animals were treated with Didymin or Silibinin from days 12 to 28. Key indicators of NAFLD were then detected, including the pathological changes of liver tissues, serum biochemical indicators, inflammation, oxidative stress, apoptosis and lipid metabolism. Besides, the expressions of pivotal genes and proteins of the TLR4/NF-κB and PI3K/Akt pathways were examined to further elucidate the mechanisms of Didymin. The results demonstrated that Didymin significantly extenuated hepatocyte damage and lipid disorder. Moreover, Didymin markedly decreased hepatocyte apoptosis by regulating the expressions of B-cell lymphoma-2 (Bcl-2) family and the expressions of the caspase family. Further study elucidated that Didymin decreased the expressions of toll-like receptor 4 (TLR4), as well as the phosphorylation of inhibitor of nuclear factor kappa-B (IκB) and nuclear factor kappa-B p65 (NF-κB p65), suggesting the inhibition of Didymin on the TLR4/NF-κB pathway. Similarly, the PI3K/Akt pathway was also inhibited by Didymin, as evidenced by the decrease in the phosphorylation levels of PI3K and Akt. In summary, this study indicates that Didymin mitigates NAFLD by alleviating lipidosis and suppressing the TLR4/NF-κB and PI3K/Akt pathways, which may be a potential natural medicine for the treatment of NAFLD.
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Flavonoides/uso terapéutico , Glicósidos/uso terapéutico , FN-kappa B/metabolismo , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Dexametasona/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/genética , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Distribución Aleatoria , Receptor Toll-Like 4/genéticaRESUMEN
Endoplasmic reticulum stress (ERS), mutual crosstalk between autophagy and apoptosis-related signaling pathway, plays an important role in the process of acute liver injury (ALI). The present study was to investigate the effects and underlying mechanisms of Asiatic acid from Potentilla chinensis (AAPC) on ALI. The model of ALI in mice was induced by administration with Lipopolysaccharide/D-Galactosamine (LPS/D-GalN). The effects of AAPC on hepatic pathology and hepatocyte apoptosis were observed by hematoxylin-eosin (H&E) staining and TUNEL staining. Serum transaminases activities were measured using an automated biochemical analyzer. Moreover, ERS and autophagy were induced in LO2 cells, respectively. Cell cycle and apoptosis were analyzed using flow cytometry. In addition, ERS and autophagy-related pathways were detected in vivo and in vitro. The results showed that AAPC significantly ameliorated LPS/D-GalN-induced ALI in mice, as evidenced by the improvement of liver pathology and the decrease in serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities. Moreover, AAPC pre-treatment markedly inhibited thapsigargin-induced cell apoptosis, accompanied by cell cycle arrest at S/G1 phase in LO2 cells. AAPC notably inhibited the activation of the PERK/ATF6 and IRE1 pathway, alleviating the extent of ERS. Additionally, AAPC significantly promoted autophagy, as evidenced by the increase in the formation of autophagic vacuoles and the number of autophagosomes as well as the increased expressions of LC3II/I, Beclin-1, Atg5 and Atg7. In summary, our results indicate that AAPC significantly ameliorates ALI by inhibiting the ERS pathway and promoting hepatocyte autophagy.
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Autofagia/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hígado/efectos de los fármacos , Triterpenos Pentacíclicos/farmacología , Animales , Apoptosis/efectos de los fármacos , Proteínas Relacionadas con la Autofagia/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Galactosamina , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Lipopolisacáridos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BLRESUMEN
Endoplasmic reticulum stress (ERS) is induced by accumulation of misfolded proteins, playing a pivotal role during the processes of non-alcoholic fatty liver disease (NAFLD). The present study was to investigate the effect of Asiatic acid from Potentilla chinensis (AAPC) on liver cell lipid metabolism, exploring the underlying mechanism of AAPC against NAFLD. In vivo, the animal NAFLD model was induced by feeding rats with high fat diet (HFD) for 18â¯weeks, and meanwhile the rats were treated with AAPC from weeks 8 to 18; In vitro experiment, the effect of AAPC on dyslipidemia induced by oleic acid (OA) in hepatic cells (HepG2) was evaluated. The results showed that AAPC significantly decreased lipidosis in rats and in HepG2 cells; it notably alleviated hepatocyte damage and lipid disturbance in rats. Moreover, the cell experiments showed that AAPC strongly inhibited HepG2 cell proliferation. It markedly decreased hepatocyte lipogenesis by regulating the key lipid metabolism-related factors, such as sterol regulatory element-binding protein 1c (SREBP-1c), encoding carboxylase, liver X Receptor Rα (LXRα), fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). The further study elucidated that AAPC treatment significantly alleviated inflammatory response by inhibiting the nuclear factor-kappa B (NF-kB) pathway. Moreover, AAPC significantly alleviated hepatocyte apoptosis and lipid metabolism disorder through reducing the extent of ERS. In conclusion, our study demonstrates that AAPC significantly ameliorates NAFLD by inhibiting the ERS pathway and lipid deposition, which may be a potential natural medicine for the treatment of NAFLD.
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Hepatocitos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Triterpenos Pentacíclicos/uso terapéutico , Animales , Células Cultivadas , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hepatocitos/fisiología , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Potentilla/inmunología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Carotid atherosclerosis (CA) and carotid plaque (CP) are highly correlated with cardiovascular disease. We aimed to determine the prevalence of CA and CP and their relationship with 10-year risks of stroke and coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM).We studied 1584 T2DM patients aged 20 years and older. CA and CP were detected using ultrasonography. Ten-year stroke and CHD risk were determined using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine.The prevalence of CA and CP increased gradually with age. Men had a higher prevalence of CA than women (CA: 58.18% vs 51.54%, Pâ<â.01). The 10-year CHD risk (27.9% vs 15.4%, Pâ<â.001) and stroke risk (15.2% vs 5.70%, Pâ<â.001) were higher in patients with CA than that of those without CA. Compared with patients without CA, the odds ratios (ORs) of CHD in CA and CP group were 4.47 and 10.78 for men, and 4.19 and 5.20 for women, respectively; in the case of stroke, the OR in CA and CP group were 8.83 and 12.07 for men, and 4.35 and 4.90 for women, respectively (Pâ<â.001 for all). Multivariate binary logistic regression analysis showed that CA was an independent risk factor for CHD [ORâ=â2.66, 95% confidence interval (95% CI), 2.05-3.46, Pâ<â.001] and stroke (ORâ=â3.11, 95% CI, 2.38-4.07, Pâ<â.001).CA and CP were prevalent in patients with T2DM and positively correlated with 10-year CHD and stroke risk. CA was an independent risk factor for 10-year CHD risk.
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Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas , Enfermedad Coronaria/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Accidente Cerebrovascular , Adulto , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/epidemiología , China/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Prospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Estadística como Asunto , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Ultrasonografía/métodos , Ultrasonografía/estadística & datos numéricosRESUMEN
We aimed to determine the relationship between lower extremity peripheral arterial disease (PAD), 10-year coronary heart disease (CHD), and stroke risks in patients with type 2 diabetes (T2DM) using the UKPDS risk engine. We enrolled 1178 hospitalized T2DM patients. The patients were divided into a lower extremity PAD group (ankle-brachial index ≤ 0.9 or >1.4; 88 patients, 7.5%) and a non-PAD group (ankle-brachial index > 0.9 and ≤1.4; 1090 patients, 92.5%). Age; duration of diabetes; systolic blood pressure; the hypertension rate; the use of hypertension drugs, ACEI /ARB, statins; CHD risk; fatal CHD risk; stroke risk; and fatal stroke risk were significantly higher in the PAD group than in the non-PAD group (P < 0.05 for all). Logistic stepwise regression analysis indicated that ABI was an independent predictor of 10-year CHD and stroke risks in T2DM patients. Compared with those in the T2DM non-PAD group, the odds ratios (ORs) for CHD and stroke risk were 3.6 (95% confidence interval (CI), 2.2-6.0; P < 0.001) and 6.9 (95% CI, 4.0-11.8; P < 0.001) in those with lower extremity PAD, respectively. In conclusion, lower extremity PAD increased coronary heart disease and stroke risks in T2DM.
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BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD). However, the association between CKD and CVD risk in patients with type 2 diabetes mellitus (T2DM) in China has not yet been well investigated. This study aimed to determine the association of CKD with the risks of coronary heart disease (CHD) and stroke in a Chinese population with T2DM. METHODS: A total of 1401 inpatients with T2DM at the Second Affiliated Hospital of Zhejiang University School of Medicine between April 2008 and November 2013 were included in this study. The CKD-Epidemiology Collaboration equation for Asians was used to classify CKD. The UK Prospective Diabetes Study risk engine was used to estimate the risks of CHD and stroke. RESULTS: CHD risk was significantly increased with CKD stage (20.1%, 24.8%, and 34.3% in T2DM patients with no CKD, CKD Stage 1-2, and Stage 3-5, respectively; P < 0.001 for all). The stroke risk was also increased with CKD stage (8.6%, 12.7%, and 25.4% in T2DM patients with no CKD, CKD Stage 1-2, and Stage 3-5, respectively; P < 0.001 for all). Compared with no-CKD group, the odds ratios (OR s) for high CHD risk were 1.7 (P < 0.001) in the CKD Stage 1-2 group and 3.5 (P < 0.001) in the CKD Stage 3-5 group. The corresponding OR s for high stroke risk were 1.9 (P < 0.001) and 8.2 (P < 0.001), respectively. CONCLUSION: In patients with T2DM, advanced CKD stage was associated with the increased risks of CHD and stroke.
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Enfermedad Coronaria/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Insuficiencia Renal Crónica/epidemiología , Accidente Cerebrovascular/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Albuminuria/orina , China , Enfermedad Coronaria/etiología , Enfermedad Coronaria/orina , Creatinina/orina , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/orina , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/orina , Adulto JovenRESUMEN
<p><b>OBJECTIVE</b>To assess the impact of metabolic syndrome(MS) on Framingham risk score(FRS) in patients with type 2 diabetes mellitus (T2DM).</p><p><b>METHODS</b>The anthropometric and biochemical data of 1708 patients with T2DM admitted in hospital from May 2008 to April 2013 were retrospectively analyzed, including 902 males and 806 females with a mean age of 57.1±11.8 years (20-79 years). Diagnosis of MS was made according to the criteria of the Adult Treatment Panel Ⅲ Criteria modified for Asians.</p><p><b>RESULTS</b>Compared to non-MS/T2DM patients, MS/T2DM patients had higher waist circumference, body weight, body mass index, systolic and diastolic blood pressure, fasting C peptide, total cholesterol, triglyceride, and LDL-C (P<0.05), while lower HDL-C (P<0.01). Both FRS [13.0(10.0, 15.0) vs 11.0(9.0, 13.0) in male,15.0(12.0, 18.0) vs 12.0(6.0, 14.8) in female,P<0.01)] and 10-year cardiovascular risk [12.0%(6.0%, 20.0%) vs 8.0%(5.0%,12.0%) in male,3.0%(1.0%, 6.0%) vs 1.0%(0.0%, 2.8%) in female,P<0.01] were higher in MS/T2DM patients than those in non-MS/T2DM patients.Both FRS and 10-year cardiovascular risk were increased with the components of MS.</p><p><b>CONCLUSION</b>T2DM patients with MS have more cardiovascular risk factors, higher FRS and 10-year cardiovascular risk.</p>
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Silver-Russell syndrome (SRS) is a rare genetic disorder with non-specific manifestations and severity, so that the clinical diagnosis of SRS remains difficult. We reported a 23-year-old female patient with SRS characterized with short body stature, asymmetry, obesity, fifth finger clinodactyly and dislocation of hip. The patient had a past history of lengthening operation on the right lower limb at the age of 10. Chromosome analysis revealed (46, XX). The patient was admitted due to severe asymmetry in low extremities caused by right-side obesity. After successful orthopedic surgery in the right hips and thighs the symptoms of patient were relieved.
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Síndrome de Silver-Russell , Femenino , Humanos , Adulto JovenRESUMEN
The association of CYP11B2 gene polymorphisms with the risk of primary aldosteronism (PA) was controversial in previous studies. Here we selected two commonly studied CYP11B2 alleles: T-344C, A2718G to explore their associations with PA risk by meta-analyses of published case-control studies. Six electronic databases were searched for relevant studies up to November 2012. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random or fixed effects model. Seven studies (621 cases and 1027 controls) on T-344C polymorphism, three studies (327 cases and 336 controls) on A2718G polymorphism were finally included. Then significant association was observed between T-344C polymorphism and idiopathic hyperaldosteronism (IHA) under three genetic models (CC vs. TT, OR=0.544, 95% CI=0.324~0.914; CT vs. TT, OR=0.554, 95% CI=0.406~0.757; CC+CT vs. TT, OR=0.542, 95% CI=0.402~0.731). But patients with aldosterone-producing adenoma had no significant association with T-344C polymorphism under all genetic models except CT vs. TT model. Concerning A2718G polymorphism, a decreased PA risk was observed only under GG+GA vs AA model. But this association disappeared after removing the studies not in Hardy-Weinberg equilibrium. The evidence accumulated suggested that -344C allele may be associated with decreased risk of IHA and there was still no enough evidence to indicate the association of A2718G polymorphism with PA risk.
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Citocromo P-450 CYP11B2/genética , Hiperaldosteronismo/genética , Estudios de Casos y Controles , Estudios de Asociación Genética/estadística & datos numéricos , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Hiperaldosteronismo/epidemiología , Polimorfismo de Nucleótido SimpleRESUMEN
The substitution effects on the geometry and the electronic structure of the ferrocene are systematically and comparatively studied using the density functional theory. It is found that -NH(2) and -OH substituents exert different influence on the geometry from -CH(3), -SiH(3), -PH(2), and -SH substituents. The topological analysis shows that all the C-C bonds in a-g are typical opened-shell interactions while the Fe-C bonds are typical closed-shell interactions. NBO analysis indicates that the cooperated interaction of d --> pi* and feedback pi --> d + 4s enhances the Fe-ligand interaction. The energy partitioning analysis demonstrates that the substituents with the second row elements lead to stronger iron-ligand interactions than those with the third row elements. The molecular electrostatic potential predicts that the electrophiles are expected to attack preferably the N, O, P, or S atoms in Fer-NH(2), Fer-OH, Fer-PH(2), and Fer-SH, and attack the ring C atoms in Fer-SiH(3) and Fer-CH(3). In turn, the nucleophiles are supposed to interact predominantly by attacking the hydrogen atoms. The simulated theoretical excitation spectra show that the maximum absorption peaks are red-shifted when the substituents going from second row elements to the third row elements.
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OBJECTIVE: To explore the changes of serum sex hormone-binding globulin (SHBG) and sex hormone levels in type 2 diabetes and to explore the correlation of SHBG with blood glucose, BMI, insulin sensitivity and the intervention of pioglitazone. METHODS: Eighty-five cases with type 2 diabetes (38 women) and 59 normal controls (27 women) were recruited randomly in the study. Among all patients 48 underwent pioglitazone intervention. All women were postmenopausal. Fasting serum samples were taken separately. SHBG were measured with IRMA, and estrogen (E2), testosterone (T), fasting insulin (FINS ) were detected with RIA. Body weight, fasting blood glucose (FBG), blood lipids,BMI, HOMA-IS were measured and calculated as well. LN [1/ (FBG x FINS)] was used as insulin sensitivity index (ISI). RESULT: Patient groups had lower serum SHBG levels than control groups of both sexes (women, P<0.01; men, P<0.05). T/SHBG are higher in women patient group compared with control (P<0.01). Spearman analysis showed that in women patient group,serum SHBG was correlated with FBG, FINS and ISI (r(s)=-0.372 P<0.05; 0.332 P<0.05; 0.445 P<0.01). While in men patient group,BMI was negatively correlated with serum SHBG and total T (r(s)= 0.329 P<0.05 and-0.424 P<0.01). Significant improvements of blood glucose and lipids were demonstrated in patients after 12-week pioglitazone intervention compared with baseline values, while serum SHBG, sex hormones and ISI had not significantly changed. CONCLUSION: Reduced serum SHBG of patients with type 2 diabetes might be related to insulin resistance to some extent.
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Diabetes Mellitus Tipo 2/sangre , Globulina de Unión a Hormona Sexual/análisis , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Hormonas Esteroides Gonadales/sangre , Humanos , Masculino , Persona de Mediana Edad , Pioglitazona , Tiazolidinedionas/uso terapéuticoRESUMEN
BACKGROUND & OBJECTIVE: The research in recent years has demonstrated that vascular endothelial growth factor-C (VEGF-C) is expressed in certain malignant tumor cells, and up to now VEGF-C is the only growth factor specific for lymphangiogenesis. The relationship between the VEGF-C expression in malignant tumor tissues and lymphatic metastasis is still scarcely reported. This study was designed to compare the VEGF-C expression in human esophageal squamous carcinoma and glioma, and then to analyze the relationship between the VEGF-C expression and tumor lymphatic metastasis. METHODS: The expression of VEGF-C antigen was detected with immunohistochemical method in 72 human esophageal squamous carcinomas (29 cases with lymph node metastasis,43 cases without lymph node metastasis) and 23 human gliomas (diagnosed pathologically as astrocytoma in grades I to IV), followed by the further analysis on the relationship between VEGF-C expression and clinicopathological parameters. RESULTS: The expression of VEGF-C antigen was not found in any gliomas, while the positive VEGF-C expression rate achieved 38.88%(28/72) in the human squamous carcinoma, with 62.07%(18/29) in the cases with lymph node metastasis, 23.26%(10/43) in the cases without lymph node metastasis, 58.82% (20/34) in the T2 and T3 of invasion depth cases, and 21.05%(8/38)in the T1 of invasion depth cases. CONCLUSION: The expression of VEGF-C antigen was significantly associated with lymph node metastasis and invasion depth in esophageal squamous carcinoma. VEGF-C may act as a key factor in the facilitation of lymphatic metastasis in esophageal squamous carcinoma.