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1.
Artículo en Inglés | MEDLINE | ID: mdl-34491893

RESUMEN

Cells of bacterial strains G9T and 7MK23T, isolated from forest soil samples collected from the Dinghushan Biosphere Reserve, Guangdong Province, PR China, were Gram-stain-negative, aerobic and rod-shaped. Strain G9T was motile with single polar flagellum and grew at 12-37 °C (optimum, 28 °C), pH 4.5-8.0 (optimum, pH 6.0-7.5) and in the presence of 0-3.5 % NaCl (optimum, 1.5%, w/v); while strain 7MK23T was non-motile and grew at 12-42 °C (optimum, 28-33 °C), pH 2.5-8.5 (optimum, pH 4.5-6.5) and NaCl levels of 0-1.0 % (optimum, 0-0.5 %, w/v). Phylogenetic analysis based on 16S rRNA gene sequences revealed that both isolates fell within the cluster of the genus Dyella. The closely related species (with a 16S rRNA gene sequence similarity >98.65%) of strain G9T were Dyella terrae JS14-6T (99.0 %), D. kyungheensis THG-B117T (98.8 %) and D. amyloliquefaciens DHC06T (98.7 %) while that of strain 7MK23T were D. mobilis DHON07T (99.2 %) and D. flava DHOC52T (99.1 %), but the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strains G9T, 7MK23T and the closely related Dyella species listed above were in the ranges of 77.5-83.8 % and 22.0-27.0 %, much lower than the species demarcation lines of 95.5 and 70 %, respectively. Phylogenomic analyses using UBCG and Phylophlan also supported that these two strains represent two novel species of Dyella. The major fatty acids of strain G9T were iso-C15 : 0, iso-C17 : 1 ω9c and iso-C17 : 0 while that of strain 7MK23T were iso-C15 : 0 and anteiso-C15 : 0. Ubiquinone-8 was the only respiratory quinone detected in both strains. The polar lipids of strain G9T consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and several unknown phospholipids, aminophospholipids, aminolipids and lipid while strain 7MK23T contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and several unknown phospholipids and aminophospholipids. The DNA G+C contents of strains G9T and 7MK23T were 64.7 and 63.4 mol%, respectively. On the basis of 16S rRNA gene sequence phylogenetic and phylogenomic analyses as well as phenotypic data obtained, we propose that strains G9T and 7MK23T represent two novel species of the genus Dyella, for which the names Dyella telluris sp. nov. (type strain G9T=KACC 21725T=GDMCC 1.2132T) and Dyella acidiphila sp. nov. (type strain 7MK23T=KCTC 62739T=GDMCC 1.1446T) are proposed.


Asunto(s)
Bosques , Gammaproteobacteria/clasificación , Filogenia , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Gammaproteobacteria/aislamiento & purificación , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
2.
Artículo en Inglés | MEDLINE | ID: mdl-33555242

RESUMEN

Three Gram-stain-negative, aerobic, motile and rod-shaped bacterial strains, 7Q-K02T, DHF22T and DHOM02T, were isolated from forest soil sampled at Dinghushan Biosphere Reserve, Guangdong Province, China. Strains 7Q-K02T, DHF22T and DHOM02T grew at 4-37, 4-42 and 12-37 °C, pH 3.0-8.5, 3.5-8.5 and 5.0-8.0, and in the presence of 0-3.0, 0-3.5 and 0-2.5 % (w/v) NaCl; with optima at 28-33, 28 and 28-33 °C, pH 3.5-6.5, 4.0-5.5 and 6.5-7.0, and 0-1.5, 0-1.5 and 0.5-1.5 % (w/v) NaCl, respectively. Strains 7Q-K02T and DHF22T have the highest 16S rRNA gene sequence similarities of 99.0 and 98.0 % to Paraburkholderia sacchari LMG 19450T and 97.7 % between themselves, while strain DHOM02T shares the highest similarity of 98.4 % to 'Burkholderia rinojensis' A396T followed by 98.3 % to Burkholderia plantarii ATCC 43733T. In the 16S rRNA gene sequence phylogram, strain 7Q-K02T formed a sister branch with Paraburkholderia sacchari, Paraburkholderia oxyphila and Paraburkholderia paradisi, and strain DHF22T was separated from all other species within the genus Paraburkholderia, while strain DHOM02T formed a separated clade with members of the genus Burkholderia. The DNA G+C contents of strains 7Q-K02T, DHF22T and DHOM02T wwe 64.3, 65.4 and 66.6 %, respectively. Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values of strains 7Q-K02T, DHF22T and closely related Paraburkholderia strains were in the ranges of 25.5-43.7 % and 81.5-91.3 %, respectively. While dDDH and ANI values between strain DHOM02T and Burkholderia strains with genome sequence data were in the ranges of 22.4-31.0 % and 78.2-86.1 %, respectively. These three strains have the same major respiratory quinone: ubiquinone-8. Strains 7Q-K02T, DHF22T and DHOM02T have C16 : 0, C17 : 0 cyclo, C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) as their major fatty acid compositions. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. On the basis of phenotypic, phylogenetic, genomic analyses and chemotaxonomic data, strains 7Q-K02T and DHF22T represent two novel species of the genus Paraburkholderia, for which the names Paraburkholderia acidiphila sp. nov. (type strain 7Q-K02T=CGMCC 1.15433T=KCTC 62472T=LMG 29209T) and Paraburkholderia acidisoli sp. nov. (type strain DHF22T=GDMCC 1.1448T=LMG 30262T) are proposed, while strain DHOM02T represents a novel species in the genus Burkholderia, for which the name Burkholderia guangdongensis sp. nov. (type strain DHOM02T=KCTC 42625T=LMG 28843T) is proposed. We also propose to transfer Burkholderia ultramafica to the genus Paraburkholderia as Paraburkholderia ultramafica comb. nov. based mainly on the results of phylogenomic analysis.

3.
Med Sci Monit ; 24: 7577-7584, 2018 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-30352988

RESUMEN

BACKGROUND Protective effects of reduced beta 2 glycoprotein I (Rb2GPI) against vascular injury of diabetes mellitus have been extensively investigated. However, the effects of Rb2GPI on liver injury in diabetic animals have not been reported. MATERIAL AND METHODS A diabetic rat model of was produced by systemic injection of streptozotocin (STZ). Rats were divided into a normal control group, a model group, and an Rb2GPI treatment group (N=6 in each group). After treatments, blood serum and liver tissue were collected to test the protection of Rb2GPI. AMP-activated protein kinase (AMPK) was detected by immunohistochemistry and Western blotting. RESULTS Our results revealed that Rß2GPI reduced blood glucose, serum creatinine, and urea nitrogen levels, as well as serum inflammation cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α and C-reactive protein in the diabetic rats. Importantly, Rß2GPI prevented liver injury in the diabetic rats as confirmed by hematoxylin-eosin (H&E) staining, alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase. Reactive oxygen species (ROS) were promoted by diabetic modeling and were attenuated by Rß2GPI administration. Moreover, Rß2GPI significantly reduced liver catalase, malondialdehyde, and superoxide dismutase levels in the diabetic rats. Rß2GPI reduced liver glycolipid storage in STZ diabetic rats. Both immunohistochemistry and Western blotting demonstrated that Rß2GPI promoted AMPK phosphorylation in the diabetic rats. CONCLUSIONS Our data proved that Rß2GPI prevented liver injury in diabetic rats, likely through activating the AMPK signaling pathway.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , beta 2 Glicoproteína I/metabolismo , beta 2 Glicoproteína I/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Glucemia/análisis , Proteína C-Reactiva/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Creatinina/análisis , Creatinina/sangre , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Modelos Animales de Enfermedad , Interleucina-6/metabolismo , Hígado/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Fosforilación , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Estreptozocina/farmacología , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
4.
J Diabetes ; 10(6): 478-486, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28303680

RESUMEN

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) has been recognized as an important player in macrophage cholesterol trafficking and inflammation, and may promote the development of atherosclerosis. To further elucidate the role of A-FABP in atherosclerosis in diabetes, we investigated the relationship between serum A-FABP concentrations and peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). METHODS: In all, 488 inpatients with T2DM were enrolled in the study (254 men, 234 women; mean (±SD) age 57.3 ± 13.0 years). The severity of peripheral arterial stenosis was assessed by ultrasound examination. Serum A-FABP concentrations were determined by ELISA. RESULTS: Serum A-FABP concentrations were significantly higher in patients with than without PAD (8.0 ± 3.3 vs 6.2 ± 1.6 ng/mL, respectively; P < 0.05). Interestingly, there was an obvious gender-related difference in PAD patients with T2DM, with the stenosis rate being higher for female than male T2DM patients in the third A-FABP tertile. Logistic regression analysis revealed that serum A-FABP concentrations were an independent risk factor for PAD in female T2DM patients (odds ratio 1.890, 95% confidence interval 1.041-3.432; P = 0.036), but not in male T2DM patients. Correlation analyses revealed that A-FABP concentrations were correlated with body mass index (BMI), diastolic blood pressure, urinary microalbumin, and serum creatinine in male patients, and with BMI, duration of T2DM, fasting blood glucose, and serum creatinine in female patients. CONCLUSIONS: Serum A-FABP concentrations are closely associated with PAD in Chinese women with T2DM. The study findings suggest that A-FABP may be a more specific marker of PAD in diabetic women than men.


Asunto(s)
Adipocitos/metabolismo , Biomarcadores/análisis , Diabetes Mellitus Tipo 2/fisiopatología , Proteínas de Unión a Ácidos Grasos/sangre , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/diagnóstico , Adipocitos/patología , Adulto , Grupo de Ascendencia Continental Asiática , Glucemia/análisis , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Hemoglobina A Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/etiología , Pronóstico , Factores de Riesgo , Factores Sexuales
5.
Am J Transl Res ; 9(9): 3935-3949, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28979671

RESUMEN

High serum beta 2 glycoprotein I (ß2GPI) is associated with complications of type 2 diabetes mellitus (DM), and especially microvascular disorders. In contrast, reduced ß2GPI (Rß2GPI) can prevent diabetic vascular injury. This study aimed to investigate the protective function of Rß2GPI in DM vascular disorders, and to assess the under lying mechanisms. High glucose-induced injury in human umbilical vein endothelial cells (HUVECs) was used to model hyperglycemia. Alow concentration of Rß2GPI (0.5 µM), but not ß2GPI, mitigated high glucose-induced cell injury. High glucose decreased miR-21 expression and Akt phosphorylation at 6 h, but facilitated their expression at 48 h. Moreover, high glucose decreased phosphatase and tensin homolog deleted on chromosome ten(PTEN) expression at 6 h, but facilitatedits expression at 48 h. Importantly, by promoting miR-21 expression, Rß2GPI mitigated high glucose-induced PTEN expression, reduced Akt phosphorylation and nitric oxide synthase activity, and increased cyclooxygenase-2 activity and cell loss. Similar to Rß2GPI, an miR-21 mimic (1 pM) and PTEN inhibition (1 µM bpV, or PTEN silencing) exerted protective action, while an Akt signaling pathway inhibitor (LY294002, 1 µM) aborted the effect of Rß2GPI on high glucose-induced cell injury. Finally, Rß2GPI inhibited high glucose-induced apoptosis via a mitochondria-dependent pathway. These data reveal that Rß2GPI exerts protective action in high glucose-induced HUVEC injury. The mechanism is related to the miR-21-PTEN-Akt pathway and mitochondria-dependent apoptosis. This study provides in vitro data supporting the therapeutic effect of Rß2GPI in diabetic vascular injury.

6.
Mol Med Rep ; 16(4): 4208-4214, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28731130

RESUMEN

Reduced ß2 glycoprotein I (ß2GPI) has been demonstrated to exhibit a beneficial effect in diabetic atherosclerosis and retinal neovascularization. However, the effect of reduced ß2GPI on vascular disorders in diabetic mellitus (DM) remains to be elucidated. The present study established a high glucose­induced injury model using human umbilical cords veins (HUVECs) and evaluated the protective effects of reduced ß2GPI against the injury. The data demonstrated that a low concentration of reduced ß2GPI (0.5 µM) mitigated high glucose­induced cell loss, decreased nitric oxide (NO) production and resulted in calcium overloading. Mechanically, reduced ß2GPI additionally reversed high glucose­induced phosphatase and tensin homolog (PTEN) accumulation, decrease of protein kinase B phosphorylation and nitric oxide synthase activity, and increase of cyclooxygenase­2 activity. It was further confirmed that PTEN inhibitor­bpV (1 µM) exhibited similar effects to those resulting from reduced ß2GPI. Overall, the data revealed that reduced ß2GPI exerts protective effects from glucose­induced injury in HUVECs, potentially via decreasing PTEN levels. The present study suggests reduced ß2GPI may act as a novel therapeutic strategy for the treatment of vascular disorders in DM.


Asunto(s)
Glucosa/toxicidad , Células Endoteliales de la Vena Umbilical Humana/patología , beta 2 Glicoproteína I/farmacología , Adulto , Calcio/metabolismo , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Femenino , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Espacio Intracelular/metabolismo , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Oxidación-Reducción , Fosfohidrolasa PTEN/metabolismo , Adulto Joven
7.
Med Sci Monit ; 23: 2715-2720, 2017 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-28578377

RESUMEN

BACKGROUND Subclinical hypothyroidism (SCH) is typically featured by elevated serum concentration of thyroid-stimulating hormone (TSH). This study aimed to determine the relationship between TSH levels and microvascular complications in type 2 diabetes patients. MATERIAL AND METHODS A total of 860 type 2 diabetes patients were enrolled in this cross-sectional study. Subjects were evaluated for anthropometric measurements, thyroid function, diabetic retinopathy, and diabetic kidney disease. TSH was divided into 3 levels: 0.27-2.49 mU/l, 2.5-4.2 mU/l, and >4.2 mU/l. RESULTS Among the participants, 76 subjects (8.8%) were diagnosed with subclinical hypothyroidism (SCH) (male: 6.6% and female: 11.8%). The prevalence of diabetic retinopathy did not differ among the groups (P=0.259). Of the 860 type 2 diabetic subjects, we further excluded invalid or missing data. Therefore, 800 and 860 subjects were included in our study of diabetic retinopathy (DR) and diabetic kidney disease (DKD), respectively. The frequencies of microalbuminuria and macroalbuminuria differed significantly among the different groups. The frequency of DKD was significantly different among the 3 groups (P=0.001) and was higher in subjects with higher TSH levels. After an adjustment for confounding variables, TSH levels were significantly associated with DKD (P<0.001). When compared with subjects with TSH 0.27-2.49 mU/l, the frequency of DKD was higher in subjects with TSH >4.20 mU/l (OR 1.531, 95% CI 1.174-1.997) and with TSH 2.50-4.20 mU/l (OR 1.579, 95% CI 1.098-2.270). However, TSH levels was not significantly correlated with DR (P=0.126). CONCLUSIONS Type 2 diabetic patients with higher TSH values had a higher prevalence of DKD.


Asunto(s)
Complicaciones de la Diabetes/sangre , Diabetes Mellitus Tipo 2/sangre , Microvasos/patología , Tirotropina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia
8.
Am J Transl Res ; 8(6): 2650-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27398148

RESUMEN

Type 2 diabetes mellitus induced atherosclerosis (DA) is regarded as a major cause of disability and death in diabetic patients. The early prediction of atherosclerosis in patients DM is necessary. Therefore, we aimed to identify special plasma microRNAs that can serve as a novel non-invasive screening signature of DA patients with atherosclerosis and test its specificity and sensitivity in the early diagnosis of DA. In total, we obtained plasma samples from 285 diabetic atherosclerosis patients and matched diabetic retinopathy (DR) patients, diabetic nephropathy (DN) patients, diabetes mellitus without complication (DM) and healthy controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). Three miRNAs were significantly increased in patients with DA compared with other groups after the multiple stages. The areas under the receiver operating characteristic (AUC) curves of the validated three-plasma miRNAs signature in DA comparing with NC were 0.881, 0.709 and 0.842 while the merged was 0.940 while DA comparing with DM was 0.879, 0.663, 0.731 and the merged was 0.928. The three miRNA could also distinguish DA from DN with an AUC of 0.894, 0.782, 0.910 and 0.963 (merged) as well as from DR with an AUC of 0.876, 0.815, 0.850 and 0.925 (merged). In conclusion, these data provide evidence that plasma miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of DA. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of DA from DR, DN, DM patients.

9.
Zhonghua Nan Ke Xue ; 20(6): 490-4, 2014 Jun.
Artículo en Chino | MEDLINE | ID: mdl-25029851

RESUMEN

OBJECTIVE: To observe the changes of the mechanical pain threshold in the rat model of autoimmune prostatitis, explore the mechanism of autoimmune prostatitis pain and offer some animal experimental evidence for the drug therapy of the condition. METHODS: Twenty male Wistar rats weighing 180 - 220 g were divided into a model and a control group. The autoimmune prostatitis model was established by subcutaneous injection of an extract of male rat prostate glands (RPG) at 60 mg/ml in Freund's complete adjuvant (FCA) and pertussis-diphtheria-tetanus vaccine at 0 and 30 days, respectively. Mechanical tactile hyperalgesia was measured once a week using Von Frey Filaments from the beginning of the study. At 8 weeks after modeling, the rats were sacrificed and the prostate tissues harvested for observation of histomorphological changes by HE staining. RESULTS: HE staining revealed different degrees of benign prostatitis in the model rats. Compared with the controls, the mechanical pain threshold in the model rats was significantly decreased with the increased time of modeling, from (65.52 +/- 6.27) g at 0 week to (23.67 +/- 4.09) g at 8 weeks (P < 0.01). Statistically significant differences were found in the variation trend at different time points between the two groups (P < 0.01). CONCLUSION: Autoimmune prostatitis models were successfully established in rats and hyperalgesia was induced after modeling.


Asunto(s)
Enfermedades Autoinmunes/fisiopatología , Umbral del Dolor/fisiología , Prostatitis/fisiopatología , Animales , Modelos Animales de Enfermedad , Masculino , Prostatitis/inmunología , Ratas , Ratas Wistar
10.
Diabetol Metab Syndr ; 6: 69, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24917890

RESUMEN

BACKGROUND: The oral DPP-4 inhibitors are new incretin-based therapies for treatment of type 2 diabetes. To assess the efficacy and safety of three DPP-4 inhibitors (Saxagliptin, Sitagliptin and Vildagliptin) as add-on therapy to dual combination of traditional oral hypoglycemic agents in Chinese type 2 diabetes patients. METHODS: In this 24-week, randomized, open-label, parallel clinical trial, we enrolled inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ≥7.5% to ≤10%) patients with type 2 diabetes, who were treated by dual combination of metformin and another traditional oral hypoglycemic agent (glimepiride, acarbose or pioglitazone). 207 patients had been randomized to add-on 5 mg saxagliptin group or 100 mg sitagliptin once daily group, or 50 mg vildagliptin twice daily group for 24 weeks. HbA1c, fasting and postprandial blood glucose (FBG and P2hBG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated. RESULT: After 24 weeks, HbA1c, FBG, and P2hBG of each group were significantly decreased. (saxagliptin vs vildagliptin vs sitagliptin: HbA1c: -1.2% vs -1.3% vs -1.1%; FBG: -1.8 mmol/l vs -2.4 mmol/l vs -1.5 mmol/l; P2hBG: -3.4 mmol/l vs -3.7 mmol/l vs -3.2 mmol/l). The changes of HbA1c and P2hBG among the three groups had no significance. However, vildagliptin-added group showed the greatest reduction (p < 0.001), while, sitagliptin-added group showed the lowest reduction (p < 0.001) in terms of FPG changes. Proportions of patients achieving HbA1c < 7% at the end were similar in three groups (saxagliptin 59%, vildagliptin 65%, sitagliptin 59%). Mild hypoglycemia was commonly reported among the three groups (saxagliptin 6%, vildagliptin 2%, sitagliptin 3%). No significant between-group difference was shown in other AEs. CONCLUSION: The three gliptins showed almost similar glycemic control and incidence of adverse events. However, for FBG control, saxagliptin demonstrated superiority to sitagliptin, while, inferiority to vildagliptin.

11.
Diabetol Metab Syndr ; 6(1): 41, 2014 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-24650537

RESUMEN

BACKGROUND: To observe the efficacy and safety of adding glimepiride to established insulin therapy in poorly controlled type 2 diabetes (T2D) and to assess the relationship of changes in the serum high-molecular weight (HMW) adiponectin levels and glycemic control after glimepiride treatment. METHODS: Fifty-six subjects with poorly controlled insulin-treated T2D were randomly assigned to either the glimepiride-added group (the group A, n = 29) or the insulin-increasing group (the group B, n = 27) while continuing current insulin-based therapy. Glycosylated hemoglobin (HbA1c) value, daily insulin dose, body weight, waist circumference, plasma lipid concentration, serum HMW adiponectin level and the number of hypoglycemic events were evaluated before and after treatment. RESULTS: At the end of study, insulin doses were significantly reduced, and the mean HbA1c, fasting blood glucose (FBG) and 2-hour postprandial blood glucose (P2BG) were improved greater in the group A compared with the group B. The serum HMW adiponectin levels were significantly increased in the group A compared with the group B. Most importantly, we found that changes in HbA1c were inversely correlated with changes in serum HMW adiponectin in the group A (r = -0.452, p = 0.02). CONCLUSIONS: Adding glimepiride to current insulin treatment led to better improvement in glycemic control with a significant smaller daily insulin dose, and the increases in the serum HMW adiponectin levels may directly contribute to improvement glycemic control.

12.
Cardiovasc Diabetol ; 13: 36, 2014 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-24498905

RESUMEN

BACKGROUND AND AIMS: Liraglutide treatment can improve glycemic control with a concomitant weight loss, but the underlying mechanism on weight loss is not completely understood. Cardiac natriuretic peptides (NPs) can resist body fat accumulation through increasing adipocytes lypolysis. In this study, we tested the hypothesis that liraglutide-induced weight loss was associated with increased plasma NPs concentrations. METHODS: Thirty-one outpatients with type 2 diabetes (T2D) treated with metformin and other oral antidiabetic drugs except for thiazolidinediones (TZDs) were subcutaneously administered with liraglutide for 12 weeks. Body composition, abdominal visceral adipose tissue areas (VAT) and subcutaneous adipose tissue areas (SAT) were assessed at pre- and post-treatment by dual-energy X-ray absorptiometry (DXA) scanning and abdominal computerized tomography (CT). Plasma atrial natriuretic peptides (ANP) and B-type ventricular natriuretic peptides (BNP) concentrations were tested by commercial ELISA Kit quantitatively. RESULTS: Following 12-week liraglutide treatment, body weight, waist circumference, total fat and lean mass, fat percentage, SAT and VAT areas were significantly reduced from baseline. Concurrently, plasma ANP and BNP levels were significantly increased following 12-week liraglutide treatment. There were significant correlations between the reductions in body compositions and the increases in both plasma ANP and BNP levels. CONCLUSIONS: There were significant correlations between increases in both plasma ANP and BNP levels and changes in liraglutide-induced body composition. Our data implied that increases in plasma NPs may add a novel dimension to explain how liraglutide induces weight loss.


Asunto(s)
Factor Natriurético Atrial/sangre , Composición Corporal/fisiología , Diabetes Mellitus Tipo 2/sangre , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido Natriurético Encefálico/sangre , Obesidad/sangre , Adulto , Biomarcadores/sangre , Composición Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Péptido 1 Similar al Glucagón/farmacología , Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Liraglutida , Masculino , Persona de Mediana Edad , Péptidos Natriuréticos/sangre , Obesidad/tratamiento farmacológico , Estudios Prospectivos
13.
Zhong Yao Cai ; 37(12): 2216-8, 2014 Dec.
Artículo en Chino | MEDLINE | ID: mdl-26080507

RESUMEN

OBJECTIVE: To study the chemical constituents of Oldenlandia diffusa. METHODS: The chemical constituents were isolated and purified by silica gel and Sephadex LH-20 column chromatography as well as recrystallization method, and their structures were elucidated on the basis of physical and spectral analyses. RESULTS: Nine compounds were isolated and their structures were identified as quercetin (1), kaempferol (2), scopoletin (3), 2-hydroxy-3-methylanthraquinone (4), 2-hydroxy-l-methoxyanthraquinone (5), α-linolenic acid (6), vanillic acid (7), p-hydroxyphenylethanol (8) and, ß-sitosterol (9). CONCLUSION: Compound 6 is obtained from this genus for the first time. Compounds 7 and 8 are obtained from this plant for the first time.


Asunto(s)
Oldenlandia/química , Fitoquímicos/química , Antraquinonas/química , Antraquinonas/aislamiento & purificación , Quempferoles/química , Quempferoles/aislamiento & purificación , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/química , Alcohol Feniletílico/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Quercetina/química , Quercetina/aislamiento & purificación , Escopoletina/química , Escopoletina/aislamiento & purificación , Sitoesteroles/química , Sitoesteroles/aislamiento & purificación , Ácido Vanílico/química , Ácido Vanílico/aislamiento & purificación , Ácido alfa-Linolénico/química , Ácido alfa-Linolénico/aislamiento & purificación
14.
Cardiovasc Diabetol ; 11: 142, 2012 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23153177

RESUMEN

OBJECTIVE: To assess the efficacy and safety of adding liraglutide to established insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and abdominal obesity compared with increasing insulin dose. METHODS: A 12-week, randomized, parallel-group study was carried out. A total of 84 patients completed the trial who had been randomly assigned to either the liraglutide-added group or the insulin-increasing group while continuing current insulin based treatment. Insulin dose was reduced by 0-30% upon the initiation of liraglutide. Insulin doses were subsequently adjusted to optimized glycemic control. Glycosylated hemoglobin (HbA1c) values, blood glucose, total daily insulin dose, body weight, waist circumference, and the number of hypoglycemic events and adverse events were evaluated. RESULTS: At the end of study, the mean reduction in HbA1c between the liraglutide-added group and the insulin-increasing group was not significantly different (1.9% vs. 1.77%, p>0.05). However, the percentage of subjects reaching the composite endpoint of HbA1c ≤ 7.0% with no weight gain and no hypoglycemia, was significantly higher in the liraglutide-added group than in the insulin-increasing group (67% vs. 19%, p<0.001). Add-on liraglutide treatment significantly reduced mean body weight (5.62 kg, p<0.01), waist circumference (5.70 cm, p<0.01), body mass index (BMI) (1.93 kg/m2, p<0.01) and daily total insulin dose (dropped by 66%) during 12-week treatment period, while all of these significantly increased with insulin increasing treatment. Add-on liraglutide treated patients had lower rate of hypoglycemic events and greater insulin and oral antidiabetic drugs discontinuation. Gastrointestinal disorders were the most common adverse events in the liraglutide added treatment, but were transient. CONCLUSIONS: Addition of liraglutide to abdominally obese, insulin-treated patients led to improvement in glycemic control similar to that achieved by increasing insulin dosage, but with a lower daily dose of insulin and fewer hypoglycemic events. Adding liraglutide to insulin also induced a significant reduction in body weight and waist circumference. Liraglutide combined with insulin may be the best treatment option for poorly controlled type 2 diabetes and abdominal obesity.


Asunto(s)
Grupo de Ascendencia Continental Asiática , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Obesidad Abdominal/etnología , Adulto , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , China/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etnología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/efectos adversos , Hemoglobina A Glucada/metabolismo , Humanos , Hipoglucemia/sangre , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Liraglutida , Masculino , Persona de Mediana Edad , Obesidad Abdominal/sangre , Obesidad Abdominal/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Circunferencia de la Cintura , Aumento de Peso/efectos de los fármacos
15.
Metab Eng ; 14(1): 1-8, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22178744

RESUMEN

Yeast flocculation is an important trait in the brewing industry as well as in ethanol production, through which biomass can be recovered by cost-effective sedimentation. However, mass transfer limitation may affect yeast growth and ethanol fermentation if the flocculation occurs earlier before fermentation is completed. In this article, a novel type of cell-cell flocculation induced by trehalose-6-phosphate synthase 1 (TPS1) promoter was presented. The linear cassette HO-P(TPS1)-FLO1(SPSC01)-KanMX4-HO was constructed to transform the non-flocculating industrial yeast S. cerevisiae 4126 by chromosome integration to obtain a new flocculating yeast strain, ZLH01, whose flocculation was induced by ethanol produced during fermentation. The experimental results illustrated that flocculation of ZLH01 was triggered by 3% (v/v) ethanol and enhanced as ethanol concentration increased till complete flocculation was achieved at ethanol concentration of 8% (v/v). Real time PCR analysis confirmed that the expression of FLO1(SPSC01) was dependent on ethanol concentration. The growth and ethanol fermentation of ZLH01 were improved significantly, compared with the constitutive flocculating yeast BHL01 engineered with the same FLO gene but directed by the constitutive 3-phosphoglycerate kinase promoter PGK1, particularly under high temperature conditions. These characteristics make the engineered yeast more suitable for ethanol production from industrial substrates under high gravity and temperature conditions. In addition, this strategy offers advantage in inducing differential expression of other genes for metabolic engineering applications of S. cerevisiae.


Asunto(s)
Etanol/metabolismo , Regulación Fúngica de la Expresión Génica/genética , Glucosiltransferasas/genética , Ingeniería Metabólica , Saccharomyces cerevisiae , Relación Dosis-Respuesta a Droga , Etanol/farmacología , Floculación , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Glucosiltransferasas/metabolismo , Fosfoglicerato Quinasa/genética , Fosfoglicerato Quinasa/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Solventes/metabolismo , Solventes/farmacología
16.
Chin Med J (Engl) ; 122(21): 2580-6, 2009 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-19951573

RESUMEN

BACKGROUND: Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease. This study aimed to test whether the antioxidant alpha-lipoic acid (alpha-LA) could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. METHODS: A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin (STZ) 45 mg/kg. Experimental animals were randomly assigned to 3 groups: normal control (NC), diabetes (DM) and DM treated with alpha-LA (alpha-LA). The latter group was administered with alpha-LA (100 mg/kg ip per day), the remainder received the same volume vehicle. At weeks 4, 8, and 12 after the onset of diabetes, cardiac apoptosis was examined by TUNEL assay. Cardiomyopathy was evaluated by assessment of cardiac structure and function. Oxidative damage was evaluated by the content of malondialdehyde (MDA), reduced glutathione (GSH) and the activity of manganese superoxide diamutase (Mn-SOD) in the myocardial mitochondria. Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blotting. RESULTS: At 4, 8, and 12 weeks after the onset of diabetes, significant reductions in TUNEL-positive cells, caspase-9,-3 expression, and mitochondrial cytochrome c release were observed in the alpha-LA group compared to the DM group. In the DM group, the content of MDA in the myocardial mitochondria was significantly increased, and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD. They were significantly improved by alpha-LA treatment. HE staining displayed structural abnormalities in diabetic hearts, while alpha-LA reversed this structural derangement. The index of cardiac function (+/-dp/dtmax) in the diabetes group was aggravated progressively from 4 weeks to 12 weeks, but alpha-LA delayed deterioration of cardiac function (P < 0.05). CONCLUSIONS: Our findings indicate that the antioxidant alpha-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy. The ability of alpha-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria.


Asunto(s)
Apoptosis/efectos de los fármacos , Cardiomiopatías/tratamiento farmacológico , Mitocondrias Cardíacas/metabolismo , Miocardio/citología , Ácido Tióctico/uso terapéutico , Animales , Caspasa 3/análisis , Caspasa 9/análisis , Glutatión/metabolismo , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Masculino , Malondialdehído/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Ácido Tióctico/farmacología
17.
Genes Cells ; 14(2): 261-70, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19170771

RESUMEN

Oxidative base damage leads to alteration of genomic information and is implicated as a cause of aging and carcinogenesis. To combat oxidative damage to DNA, cells contain several DNA glycosylases including OGG1, NTH1 and the Nei-like proteins, NEIL1 and NEIL2. A third Nei-like protein, NEIL3, is composed of an amino-terminal Nei-like domain and an unknown carboxy-terminal domain. In contrast to the other well-described DNA glycosylases, the DNA glycosylase activity and in vivo repair function of NEIL3 remains unclear. We show here that the structural modeling of the putative NEIL3 glycosylase domain (1-290) fits well to the known Escherichia coli Fpg crystal structure. In spite of the structural similarity, the recombinant NEIL3 and NEIL3(1-290) proteins do not cleave any of several test oligonucleotides containing a single modified base. Within the substrates, we detected AP lyase activity for single-stranded (ss) DNA but double-stranded (ds) DNA. The activity is abrogated completely in mutants with an amino-terminal deletion and at the zinc-finger motif. Surprisingly, NEIL3 partially rescues an E. coli nth nei mutant from hydrogen peroxide sensitivity. Taken together, repair of certain base damage including base loss in ssDNA may be mediated by NEIL3.


Asunto(s)
ADN de Cadena Simple/metabolismo , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Escherichia coli/genética , Estrés Oxidativo/genética , Secuencia de Aminoácidos , Animales , ADN Glicosilasas/química , ADN Glicosilasas/genética , ADN Glicosilasas/metabolismo , ADN-(Sitio Apurínico o Apirimidínico) Liasa/química , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , ADN-Formamidopirimidina Glicosilasa/química , Resistencia a Medicamentos/genética , Escherichia coli/enzimología , Escherichia coli/metabolismo , Escherichia coli/fisiología , Proteínas de Escherichia coli/química , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Datos de Secuencia Molecular , N-Glicosil Hidrolasas/química , N-Glicosil Hidrolasas/genética , N-Glicosil Hidrolasas/metabolismo , Organismos Modificados Genéticamente , Oxidantes/farmacología , Unión Proteica , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Especificidad por Sustrato
18.
Mutagenesis ; 23(5): 407-13, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18524757

RESUMEN

Uracil arises in DNA from spontaneous deamination of cytosine and through incorporation of dUMP by DNA polymerase during DNA replication. Excision of uracil by the action of uracil-DNA glycosylase (Ung) initiates the base excision repair pathway to counter the promutagenic base modification. In this study, we cloned a cDNA-encoding Caenorhabditis elegans homologue (CeUng-1) of Escherichia coli Ung. There was 49% identity in amino acid sequence between E.coli Ung and CeUng-1. Purified CeUng-1 removed uracil from both U:G and U:A base pairs in DNA. It also removed uracil from single-stranded oligonucleotide substrate less efficiently than double-stranded oligonucleotide. The CeUng-1 activity was inhibited by Bacillus subtilis Ung inhibitor, indicating that CeUng-1 is a member of the family-1 Ung group. The mutation in the ung-1 gene did not affect development, fertility and lifespan in C.elegans, suggesting the existence of backup enzyme. However, we could not detect residual uracil excision activity in the extract derived from the ung-1 mutant. The present experiments also showed that the ung-1 mutant of C.elegans was more resistant to NaHSO(3)-inducing cytosine deamination than wild-type strain.


Asunto(s)
Caenorhabditis elegans/enzimología , Uracil-ADN Glicosidasa/metabolismo , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Clonación Molecular , Secuencia Conservada , Citosina/metabolismo , Desaminación , Datos de Secuencia Molecular , Mutación , Estructura Terciaria de Proteína , Sulfitos/toxicidad , Uracil-ADN Glicosidasa/genética
19.
J Radiat Res ; 48(5): 417-24, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17641464

RESUMEN

Bacteria and eukaryotes possess redundant enzymes that recognize and remove oxidatively damaged bases from DNA through base excision repair. DNA glycosylases remove damaged bases to initiate the base excision repair. The exocyclic methyl group of thymine does not escape oxidative damage to produce 5-formyluracil (5-foU) and 5-hydroxymethyluracil (5-hmU). 5-foU is a potentially mutagenic lesion. A homolog of E. coli endonuclease III (SpNth1) had been identified and characterized in Schizosaccharomyces pombe. In this study, we found that SpNth1 recognizes and removes 5-foU and 5-hmU from DNA with similar efficiency. The specific activities for the removal of 5-foU and 5-hmU were comparable with that for thymine glycol. The expression of SpNth1 reduced the hydrogen peroxide toxicity and the frequency of spontaneous mutations in E. coli nth nei mutant. It was also revealed that SpNth1 had DNA glycosylase activity for removing 8-oxo-7,8-dihydroguanine (8-oxoG) from 8-oxoG/G and 8-oxoG/A mispairs. These results indicated that SpNth1 has a broad substrate specificity and is involved in the base excision repair of 8-oxoG and thymine residues oxidized in the methyl group in S. pombe.


Asunto(s)
ADN Glicosilasas/genética , ADN Glicosilasas/metabolismo , Reparación del ADN/fisiología , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Complejos Multienzimáticos/genética , Complejos Multienzimáticos/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Metilación de ADN , Guanina/química , Guanina/metabolismo , Oxidación-Reducción , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Schizosaccharomyces/enzimología , Schizosaccharomyces/genética , Timina/química , Timina/metabolismo
20.
Mutagenesis ; 22(3): 183-8, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17267816

RESUMEN

DNA polymerase beta (Pol beta) is important for the base excision repair (BER) pathway. Overexpression of Pol beta is frequently found in cancer cells and is thought to be associated with tumorigenesis. In this study, we examined BER fidelity in extracts derived from a human lymphoblastoid cell line that over expresses Pol beta compared to normal control cells. Using an in vitro mutagenesis assay, we found an increased rate of frameshift mutations arising during DNA repair in whole-cell extracts derived from the Pol beta-overexpressing cells. We demonstrate that the addition of excess Pol beta to a control cell extract enhances the mutagenic potential of the extract. Furthermore, using cell extracts and purified Pol beta, we demonstrate that the mechanism of frameshift formation involves slippage of Pol beta during the one-nucleotide gap-filling step of BER and that this slippage is fixed by strand-displacement synthesis stimulated by an excess of Pol beta.


Asunto(s)
ADN Polimerasa beta/farmacología , Reparación del ADN/fisiología , Mutación del Sistema de Lectura/efectos de los fármacos , Secuencia de Bases , Western Blotting , Línea Celular Tumoral , ADN Polimerasa beta/metabolismo , Replicación del ADN/fisiología , Escherichia coli , Mutación del Sistema de Lectura/fisiología , Regulación Enzimológica de la Expresión Génica/fisiología , Humanos , Datos de Secuencia Molecular , Oligonucleótidos
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