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1.
Osteoporos Int ; 35(6): 1049-1059, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38459138

RESUMEN

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.


Asunto(s)
Densidad Ósea , Hueso Esponjoso , Húmero , Tomografía Computarizada por Rayos X , Humanos , Densidad Ósea/fisiología , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Reproducibilidad de los Resultados , Húmero/diagnóstico por imagen , Húmero/fisiología , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/fisiopatología , Hueso Esponjoso/fisiología , Algoritmos , Fantasmas de Imagen , Adulto , Osteoporosis/fisiopatología , Osteoporosis/diagnóstico por imagen , Anciano de 80 o más Años
2.
BMC Cardiovasc Disord ; 24(1): 33, 2024 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-38184555

RESUMEN

OBJECTIVE: To investigate the association between circulating secretoneurin (SN) and angiographic coronary collateralization in stable angina patients with chronic coronary total occlusion (CTO). METHODS: SN concentrations in serum were measured in 641 stable angina patients with CTO by radioimmunoassay. The status of coronary collaterals from the contra-lateral vessel was visually estimated using the Rentrop grading system, and was categorized into poor (grade 0 or 1) or good (grade 2 or 3) collateralization. RESULTS: Serum SN levels were significantly higher in patients with good coronary collaterals compared to those with poor collaterals (175.23 ± 52.09 pmol/L vs. 143.29 ± 42.01 pmol/L, P < 0.001). Serum SN increased stepwise across Rentrop score 0 to 3 (P < 0.001), and increasing SN tertiles were associated with higher proportion of good coronary collateralization (OR, 1.907; 95% CI, 1.558 ~ 2.335, P < 0.001). After adjustment for confounding variables, serum SN (per tertile) remained an independent factor for predicting good coronary collaterals (OR, 1.870; 95% CI, 1.515 ~ 2.309; P < 0.001). Moreover, the diagnostic value of serum SN (per tertile) was consistent after stratifying patients based on gender, age, body mass index, hypertension, diabetes, history of smoking, severity of coronary artery disease and kidney function (OR: 1.511 ~ 2.680, P interaction ≥ 0.327). CONCLUSION: Elevated circulating SN reflects good angiographic coronary collaterals in stable angina patients with CTO. The findings may provide insight into decision-making for these patients.


Asunto(s)
Angina Estable , Hipertensión , Neuropéptidos , Humanos , Angina Estable/diagnóstico por imagen , Corazón
3.
Int J Mol Sci ; 25(4)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38396816

RESUMEN

Focal adhesions (FAs) play a crucial role in cell spreading and adhesion, and their autophagic degradation is an emerging area of interest. This study investigates the role of Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) in regulating autophagy and FA stability in brain endothelial cells, shedding light on its potential implications for cerebrovascular diseases. Our research reveals a physical interaction between THSD1 and FAs. Depletion of THSD1 significantly reduces FA numbers, impairing cell spreading and adhesion. The loss of THSD1 also induces autophagy independently of changes in mTOR and AMPK activation, implying that THSD1 primarily governs FA dynamics rather than serving as a global regulator of nutrient and energy status. Mechanistically, THSD1 negatively regulates Beclin 1, a central autophagy regulator, at FAs through interactions with focal adhesion kinase (FAK). THSD1 inactivation diminishes FAK activity and relieves its inhibitory phosphorylation on Beclin 1. This, in turn, promotes the complex formation between Beclin 1 and ATG14, a critical event for the activation of the autophagy cascade. In summary, our findings identify THSD1 as a novel regulator of autophagy that degrades FAs in brain endothelial cells. This underscores the distinctive nature of THSD1-mediated, cargo-directed autophagy and its potential relevance to vascular diseases due to the loss of endothelial FAs. Investigating the underlying mechanisms of THSD1-mediated pathways holds promise for discovering novel therapeutic targets in vascular diseases.


Asunto(s)
Adhesiones Focales , Trombospondinas , Enfermedades Vasculares , Humanos , Autofagia , Beclina-1/metabolismo , Células Endoteliales/metabolismo , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Adhesiones Focales/metabolismo , Fosforilación , Enfermedades Vasculares/metabolismo , Trombospondinas/metabolismo
4.
BMC Geriatr ; 23(1): 404, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-37400759

RESUMEN

BACKGROUND: Previous studies have shown that type 2 diabetes mellitus (T2DM) can cause sarcopenia; however, these conditions may have a bidirectional association. This study aimed to explore the longitudinal association between possible sarcopenia and new-onset T2DM. METHODS: We conducted a population-based cohort study using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). This study included participants aged ≥ 60 years who were free of diabetes during the baseline survey of CHARLS (2011 to 2012) and were followed up until 2018. Possible sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Cox proportional hazards regression models were used to evaluate the effect of possible sarcopenia on new-onset T2DM. RESULTS: In total, 3,707 individuals were enrolled in this study, with a median age of 66 years; the prevalence of possible sarcopenia was 45.1%. During the 7-year follow-up, 575 cases (15.5%) of incident diabetes were identified. Participants with possible sarcopenia were more likely to have new-onset T2DM than those without possible sarcopenia (hazard ratio: 1.27, 95% confidence interval: 1.07-1.50; p = 0.006). In subgroup analysis, we found a significant association between possible sarcopenia and T2DM in individuals aged < 75 years or with a BMI < 24 kg/m². However, this association was not significant in individuals aged ≥ 75 years or with a BMI ≥ 24 kg/m². CONCLUSIONS: Possible sarcopenia is associated with an increased risk of new-onset T2DM in older adults, especially in individuals who are not overweight and aged 75 years or younger.


Asunto(s)
Diabetes Mellitus Tipo 2 , Sarcopenia , Humanos , Anciano , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Estudios de Cohortes , Estudios Longitudinales , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Sarcopenia/complicaciones , Jubilación , China/epidemiología , Factores de Riesgo
5.
Plant Foods Hum Nutr ; 78(2): 439-444, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37351712

RESUMEN

Mung bean is a kind of legume commonly eaten by human. In the present study, a HPLC method for analyzing of two C-glycoside flavonoids, isovitexin and vitexin, in Mung bean was developed. Results showed that the flavonoids are mainly existed in Mung bean coat (MBC), while kernel contains very trace. The extraction of C-glycoside flavonoids from MBC was optimized. MBC extracts with isovitexin and vitexin contents of 29.0 ± 0.28% and 35.8 ± 0.19% were obtained with yield of 1.6 ± 0.21%. MBC extracts exhibited inhibitory activities on pancreatic lipase and α-glucosidase with IC50 values of 0.147 mg/ml and 0.226 mg/ml, respectively. The inhibitory kinetics revealed that MBC extracts showed mixed-type inhibition on these enzymes. Fluorescence quenching titration confirmed the binding of MBC extracts with the enzyme proteins. In vivo study revealed that pre-administration with MBC extracts significantly reduced the triglyceride absorption. Furthermore, it also improved postprandial hyperglycemia in rats through the inhibition of α-glucosidase.


Asunto(s)
Fabaceae , Vigna , Ratas , Humanos , Animales , Flavonoides/farmacología , Flavonoides/química , Lipasa , alfa-Glucosidasas/metabolismo , Vigna/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fabaceae/química
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(10): 1034-1039, 2023 Oct 15.
Artículo en Zh | MEDLINE | ID: mdl-37905760

RESUMEN

OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS: For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.


Asunto(s)
Miastenia Gravis , Tacrolimus , Humanos , Niño , Prednisona/efectos adversos , Tacrolimus/efectos adversos , Estudios Retrospectivos , Actividades Cotidianas , Inmunosupresores/efectos adversos , Miastenia Gravis/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Ácido Micofenólico/efectos adversos
7.
BMC Nephrol ; 22(1): 66, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33622294

RESUMEN

BACKGROUND: Sulfation of tyrosine, yielding O-sulfotyrosine, is a common but fixed post-translational modification in eukaryotes. Patients with increased circulating O-sulfotyrosine levels experience a faster decline in renal function with progression to end-stage renal disease (ESRD). In the present study, we measured serum O-sulfotyrosine levels in individuals with chronic kidney disease (CKD) and acute kidney injury (AKI) to explore its ability to differentiate AKI from CKD. METHODS: A total of 135 patients (20 with AKI and 115 with CKD) were recruited prospectively for liquid chromatography-mass spectrometry assessment of circulating O-sulfotyrosine. We also studied C57BL/6 mice with CKD after 5/6 nephrectomy (Nx). Blood samples were drawn from the tail vein on Day 1, 3, 5, 7, 14, 30, 60, and 90 after CKD. Serum separation and characterization of creatinine, blood urea nitrogen (BUN), and O-sulfotyrosine was performed. Thus, the time-concentration curves of the O-sulfotyrosine level demonstrate the variation of kidney dysfunction. RESULTS: The serum levels of O-sulfotyrosine were markedly increased in patients with CKD compared with AKI. Median O-sulfotyrosine levels in CKD patients versus AKI, respectively, were as follows:243.61 ng/mL(interquartile range [IQR] = 171.90-553.86) versus 126.55 ng/mL (IQR = 48.19-185.03, P = 0.004). In patients with CKD, O-sulfotyrosine levels were positively correlated with creatinine, BUN, and Cystatin C (r = 0.63, P < 0.001; r = 0.49, P < 0.001; r = 0.61, P < 0.001, respectively) by the multivariate linear regression analysis (ß = 0.71, P < 0.001; ß = 0.40, P = 0.002; ß = 0.73, P < 0.001, respectively). However, this association was not statistically significant in patients with AKI (r = - 0.17, P = 0.472; r = 0.11, P = 0.655; r = 0.09, P = 0.716, respectively). The receiver operating characteristic (ROC) analysis illustrated that the area under the curve was 0.80 (95% confidence interval [CI] 0.71-0.89; P < 0.001) and the optimal cut-off value of serum O-sulfotyrosine suggesting AKI was < 147.40 ng/mL with a sensitivity and specificity of 80.90 and 70.00% respectively. In animal experiments, serum levels of O-sulfotyrosine in mice were elevated on Day 7 after 5/6 nephrectomy (14.89 ± 1.05 vs. 8.88 ± 2.62 ng/mL, P < 0.001) until Day 90 (32.65 ± 5.59 vs. 8.88 ± 2.62 ng/mL, P < 0.001). CONCLUSION: Serum O-sulfotyrosine levels were observed correlated with degrading renal function and in CKD patients substantially higher than those in AKI patients. Thus serum O-sulfotyrosine facilitated the differential diagnosis of AKI from CKD.


Asunto(s)
Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Tirosina/análogos & derivados , Anciano , Animales , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Tirosina/sangre
8.
J Cell Physiol ; 235(5): 4655-4666, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31637713

RESUMEN

Podosomes and tight junctions (TJs) are subcellular compartments that both exist in endothelial cells and localize at cell surfaces. In contrast to the well-characterized role of TJs in maintaining cerebrovascular integrity, the specific function of endothelial podosomes remains unknown. Intriguingly, we discovered cross-talk between podosomes and TJs in human brain endothelial cells. Tight junction scaffold proteins ZO-1 and ZO-2 localize at podosomes in response to phorbol-12-myristate-13-acetate treatment. We found that both ZO proteins are essential for podosome formation and function. Rather than being derived from new protein synthesis, podosomal ZO-1 and ZO-2 are relocated from a pre-existing pool found at the peripheral plasma membrane with enhanced physical interaction with cortactin, a known protein marker for podosomes. Sequestration of ZO proteins in podosomes weakens tight junction complex formation, leading to increased endothelial cell permeability. This effect can be further attenuated by podosome inhibitor PP2. Altogether, our data revealed a novel cellular function of podosomes, specifically, their ability to negatively regulate tight junction and endothelial barrier integrity, which have been linked to a variety of cerebrovascular diseases.


Asunto(s)
Encéfalo/irrigación sanguínea , Células Endoteliales/metabolismo , Podosomas/metabolismo , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Proteína de la Zonula Occludens-2/metabolismo , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Humanos , Permeabilidad , Podosomas/efectos de los fármacos , Multimerización de Proteína , Transporte de Proteínas , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/farmacología , Uniones Estrechas/efectos de los fármacos , Proteína de la Zonula Occludens-1/genética , Proteína de la Zonula Occludens-2/genética
9.
Cardiovasc Diabetol ; 19(1): 131, 2020 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-32878604

RESUMEN

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to poor cardiovascular outcomes after ST-segment elevation myocardial infarction (STEMI). Left ventricular adverse remodeling (LVAR) triggered upon myocardial infarction is recognized as the predominant pathological process in the development of heart failure. In the present study, we sought to investigate whether visit-to-visit fasting plasma glucose (FPG) variability is a potential predictor of LVAR in T2DM patients after STEMI. METHODS: From January 2014 to December 2018 in Ruijin Hospital, T2DM patients with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for ~ 12 months. The changes in left ventricular geometric and functional parameters between baseline and 12-month follow-up were assessed by echocardiography. The incidence of LVAR, defined as 20% increase in indexed left ventricular end-diastolic volume (LVEDV), and its relationship with visit-to-visit FPG variability were analyzed. Multivariate regression models were constructed to test the predictive value of FPG variability for post-infarction LVAR. RESULTS: A total of 437 patients with type 2 diabetes and STEMI were included in the final analysis. During a mean follow-up of 12.4 ± 1.1 months, the incidence of LVAR was 20.6% and mean enlargement of indexed LVEDV was 3.31 ± 14.4 mL/m2, which was significantly increased in patients with higher coefficient variance (CV) of FPG (P = 0.002) irrespective of baseline glycemic levels. In multivariate analysis, FPG variability was independently associated with incidence of post-infarction LVAR after adjustment for traditional risk factors, baseline HbA1c as well as mean FPG during follow-up (OR: 3.021 [95% CI 1.081-8.764] for highest vs. lowest tertile of CV of FPG). Assessing FPG variability by other two measures, including standard deviation (SD) and variability independent of the mean (VIM), yielded similar findings. CONCLUSIONS: This study suggests that visit-to-visit FPG variability is an independent predictor of incidence of LVAR in T2DM patients with STEMI. Trial registration Trials number, NCT02089360; registered on March 17,2014.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/terapia , Función Ventricular Izquierda , Remodelación Ventricular , Anciano , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Ayuno/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
10.
Cardiovasc Diabetol ; 19(1): 59, 2020 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-32393276

RESUMEN

BACKGROUND: To assess the prognostic role of coronary collaterals in patients with type 2 diabetes mellitus (T2DM) after successful percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS: Coronary collateralization was graded according to Rentrop scoring system in 198 type 2 diabetic patients and 335 non-diabetics with stable angina undergoing PCI for at least one CTO lesion. Left ventricular ejection fraction (LVEF) was determined and major adverse cardio-cerebral events (MACCE) were recorded during follow-up. RESULTS: Poor collateralization was more common in patients with T2DM than in non-diabetics (40% vs 29%, p = 0.008). At 13.5 ± 4.1 months, the rate of composite MACCE (17.3% vs 27.6%, p = 0.034) and repeat revascularization (15.2% vs 25.5%, p = 0.026) was lower and the increase in LVEF (3.10% vs 1.80%, p = 0.024) was greater in patients with good collaterals than in those with poor collaterals for non-diabetic group. The associations were in the same direction for T2DM group (35% vs 44%; 30% vs 36%; 2.14% vs 1.65%, respectively) with a higher all-cause mortality in diabetic patients with poor collaterals (p = 0.034). Multivariable Cox proportional hazards analysis showed that coronary collateralization was an independent factor for time to MACCE (HR 2.155,95% CI 1.290-3.599, p = 0.003) and repeat revascularization (HR 2.326, 95% CI 1.357-3.986, p = 0.002) in non-diabetic patients, but did not enter the model in those with T2DM. CONCLUSIONS: T2DM is associated with reduced coronary collateralization. The effects of the status of coronary collateralization on long-term clinical outcomes and left ventricular function appear to be similar in size in type 2 diabetic patients and non-diabetics after successful recanalization of CTO.


Asunto(s)
Circulación Colateral , Circulación Coronaria , Oclusión Coronaria/terapia , Diabetes Mellitus Tipo 2/fisiopatología , Intervención Coronaria Percutánea , Anciano , Enfermedad Crónica , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/mortalidad , Oclusión Coronaria/fisiopatología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Estudios Prospectivos , Recuperación de la Función , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Función Ventricular Izquierda
11.
Cardiovasc Diabetol ; 19(1): 133, 2020 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-32887588

RESUMEN

BACKGROUND: Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation. METHODS: We consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR. RESULTS: From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P < 0.001), and this trend was more prominent in patients with optimal glycemic control (HbA1c ≤ 7%) in the baseline. In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI 1.14-7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing HbA1c variability by SD or VIM yielded similar findings. CONCLUSIONS: This study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation. Trial registration NCT02089360: NCT.


Asunto(s)
Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/terapia , Reestenosis Coronaria/epidemiología , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/metabolismo , Intervención Coronaria Percutánea/instrumentación , Anciano , Biomarcadores/sangre , China/epidemiología , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Reestenosis Coronaria/diagnóstico por imagen , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Stents , Factores de Tiempo , Resultado del Tratamiento
12.
Hepatol Res ; 50(1): 110-120, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31661588

RESUMEN

AIM: Our previous transcriptome sequencing analysis detected that retinol dehydrogenase 16 (RDH16) was dramatically downregulated in hepatocellular carcinoma (HCC). RDH16 belongs to the short-chain dehydrogenases/reductases super family, and its role in HCC remains unknown. This study aimed to investigate the expression and function of RDH16 in HCC. METHODS: The mRNA and protein level of RDH16 in HCC samples were detected by quantitative real-time polymerase chain reaction and immunohistochemistry analyses, respectively. The role of RDH16 in HCC was determined by in vitro and in vivo functional studies. RESULTS: Downregulation of RDH16 has been detected in approximately 90% of primary HCCs, which was significantly associated with high serum alpha-fetoprotein level, tumor size, microsatellite formation, thrombus, and poor overall survival of HCC patients. Compared with non-tumor tissues, higher density of methylation was identified in HCC samples. In addition, RDH16 increases the level of retinoic acid and blocks the de novo synthesis of fatty acid in HCC cells. Functional study shows that ectopic expression of RDH16 in HCC cells suppresses cell growth, clonogenicity, and cell motility. CONCLUSIONS: RDH16 might be a prognostic biomarker and intervention point for new therapeutic strategies in HCC.

13.
Lipids Health Dis ; 19(1): 246, 2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33256742

RESUMEN

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12944-020-01416-2.

14.
Cardiovasc Diabetol ; 18(1): 160, 2019 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-31733658

RESUMEN

BACKGROUND: Controversies exist regarding the optimal blood pressure (BP) level that is safe and provides cardiovascular protection in patients with type 2 diabetes mellitus (T2DM) and coexistent coronary artery disease. Several new glucose-lowering agents have been found to lower BP as well, making the interaction between BP and T2DM even more complex. METHODS: With the reference to recent literature, this review article describes the potential mechanisms of increased risk of hypertension in T2DM and outlines the possible optimal BP levels based upon recommendations on the management of hypertension by the current guidelines, in combination with our research findings, for type 2 diabetic patients with coronary artery disease. RESULTS: The development of hypertension in T2DM involves multiple processes, including enhanced sympathetic output, inappropriate activation of renin-angiotensin- aldosterone system, endothelial dysfunction induced through insulin resistance, and abnormal sodium handling by the kidney. Both AGE-RAGE axis and adipokine dysregulation activate intracellular signaling pathways, increase oxidative stress, and aggravate vascular inflammation. Pancreatic ß-cell specific microRNAs are implicated in gene expression and diabetic complications. Non-pharmacological intervention with lifestyle changes improves BP control, and anti-hypertensive medications with ACEI/ARB, calcium antagonists, ß-blockers, diuretics and new hypoglycemic agent SGLT2 inhibitors are effective to decrease mortality and prevent major adverse cardiovascular events. For hypertensive patients with T2DM and stable coronary artery disease, control of BP < 130/80 mmHg but not < 120/70 mmHg is reasonable, whereas for those with chronic total occlusion or acute coronary syndromes, an ideal BP target may be somewhat higher (< 140/90 mmHg). Caution is advised with aggressive lowering of diastolic BP to a critical threshold (< 60 mmHg). CONCLUSIONS: Hypertension and T2DM share certain similar aspects of pathophysiology, and BP control should be individualized to minimize adverse events and maximize benefits especially for patients with T2DM and coronary artery disease.


Asunto(s)
Antihipertensivos/uso terapéutico , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Enfermedad de la Arteria Coronaria/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Humanos , Hipertensión/sangre , Hipertensión/epidemiología , Hipertensión/fisiopatología , Factores de Riesgo , Resultado del Tratamiento
15.
Cardiovasc Diabetol ; 18(1): 100, 2019 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-31391045

RESUMEN

BACKGROUND: Adverse cardiac remodeling after ST-segment elevation myocardial infarction (STEMI) is a major cause for poor cardiovascular outcomes such as heart failure. The predisposing factors and underlying mechanisms remain not fully understood. This study investigates the association of insulin resistance and dysglycemia with left ventricular (LV) remodeling after STEMI in non-diabetic patients. METHODS: A total of 485 non-diabetic subjects with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for 12 months. Relation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and glucose levels to changes in echocardiography parameters was studied. RESULTS: Left ventricular dilation was detected in 49.1% of subjects at 12-month follow-up after STEMI, and was more severe in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and high HOMA-IR levels. HOMA-IR remained correlated to changes in LV dimensions after adjusting for confounding risk factors. Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI. A significant interaction term was present between HOMA-IR and IGT in the model (P = 0.001). CONCLUSIONS: Our study reveals that insulin resistance and dysglycemia are prevalent in non-diabetic patients with STEMI and are predictors of the post-infarction LV dilation. Trial registration Trials number, NCT02089360; registered on March 17, 2014.


Asunto(s)
Glucemia/metabolismo , Intolerancia a la Glucosa/sangre , Resistencia a la Insulina , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/terapia , Función Ventricular Izquierda , Remodelación Ventricular , Biomarcadores/sangre , China/epidemiología , Intolerancia a la Glucosa/diagnóstico , Intolerancia a la Glucosa/epidemiología , Humanos , Intervención Coronaria Percutánea/efectos adversos , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
16.
Cardiovasc Diabetol ; 18(1): 82, 2019 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-31234867

RESUMEN

BACKGROUND: We investigated whether or to what extent the interaction of lipoprotein (a) [Lp(a)] with cholesterol-containing lipids was associated with angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion. METHODS: Serum levels of Lp(a), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglyceride were determined and non-HDL-C was calculated in 706 type 2 diabetic and 578 non-diabetic patients with stable coronary artery disease and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary collateralization (Rentrop score of 2 or 3). RESULTS: For diabetic and non-diabetic patients, Lp(a), total cholesterol, LDL-C, and non-HDL-C levels were higher in patients with poor coronary collateralization than in those with good collateralization, whereas HDL-C and triglyceride levels were similar. After adjustment for potential confounding factors, tertiles of Lp(a), total cholesterol, LDL-C and non-HDL-C remained independent determinants for poor collateralization. A significant interaction between Lp(a) and total cholesterol, LDL-C or non-HDL-C was observed in diabetic patients (all P interaction < 0.001) but not in non-diabetics. At high tertile of total cholesterol (≥ 5.35 mmol/L), LDL-C (≥ 3.36 mmol/L) and non-HDL-C (≥ 4.38 mmol/L), diabetic patients with high tertile of Lp(a) (≥ 30.23 mg/dL) had an increased risk of poor collateralization compared with those with low tertile of Lp(a) (< 12.66 mg/dL) (adjusted OR = 4.300, 3.970 and 4.386, respectively, all P < 0.001). CONCLUSIONS: Increased Lp(a) confers greater risk for poor coronary collateralization when total cholesterol, LDL-C or non-HDL-C are elevated especially for patients with type 2 diabetes.


Asunto(s)
Colesterol/sangre , Circulación Colateral , Angiografía Coronaria , Circulación Coronaria , Oclusión Coronaria/etiología , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/complicaciones , Lipoproteína(a)/sangre , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , LDL-Colesterol/sangre , Enfermedad Crónica , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/fisiopatología , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Dislipidemias/sangre , Dislipidemias/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Triglicéridos/sangre
18.
Anticancer Drugs ; 30(10): 1022-1030, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31283543

RESUMEN

Osthole is an antitumor compound, which effect on Gallbladder cancer (GBC) has been not elucidated. This study focused on its anti-GBC effect and mechanism both in vitro and in vivo. The antiproliferation effect on cell lines NOZ and SGC-996 were measured by cell counting kit-8 (CCK-8) and colony formation assay. The effects on cell apoptosis and cell cycle were investigated by flow cytometry assay. The migration effect was checked by transwell assay and the expressions of proteins were examined by Western Blots. Also, we did an in-vivo experiment by intraperitoneal injection of osthole in nude mice. The results showed that cell proliferation and viability were inhibited in a dose- and time-dependent manner. The similar phenomenon was also found in vivo. Flow cytometric assay confirmed that osthole inhibited cells proliferation via inducing apoptosis and G2/M arrest. Transwell assay indicated that osthole inhibited the migration in a dose-dependent manner. Expression of key proteins related with apoptosis and cell cycle were testified after osthole treatment. Also, we found the key proteins involved in the JAK/STAT3 signal way decreased after osthole treatment. This study suggested that osthole can inhibit the progression of human GBC cell lines, thus maybe a potential drug for GBC treatment.


Asunto(s)
Antineoplásicos/farmacología , Cumarinas/farmacología , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Factor de Transcripción STAT3/metabolismo , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/patología , Humanos , Quinasas Janus/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Nanomedicine ; 18: 303-314, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30326275

RESUMEN

Development of combined chemo-photothermal nanoplatform is of great interest for enhancing antitumor efficacy. Herein, a multifunctional drug delivery system was synthesized based on gold-nanobranched coated betulinic acid liposomes (GNBS-BA-Lips) for chemo-photothermal synergistic therapy. In this system, GNBS-BA-Lips exhibited broad near-infrared (NIR) absorption, preferable photothermal response and good photostability under NIR irradiation. Importantly, the gold-nanobranched nanostructure possessed high photothermal conversion efficiency (η = 55.7%), and the temperature change (ΔT) reached 43.2 °C after laser irradiation for 5 min. Upon NIR irradiation, the nanocarriers apparently endowed higher cell uptake, resulting in an enhanced intracellular drug accumulation. Furthermore, the tumor growth inhibition ratio achieved from chemo-photothermal therapy of GNBS-BA-Lips was 86.9 ±â€¯1.1%, which was higher than that of the chemotherapy or photothermal therapy alone, showing an outstanding synergistic anticancer effect. Our data suggested that the nanoplatform should be considered as a critical platform in the development of cancer multi-mode therapies.


Asunto(s)
Antineoplásicos/farmacología , Portadores de Fármacos/química , Oro/química , Hipertermia Inducida , Nanocáscaras/química , Fototerapia , Supervivencia Celular/efectos de los fármacos , Composición de Medicamentos , Endocitosis/efectos de los fármacos , Células HeLa , Humanos , Liposomas , Nanocáscaras/ultraestructura , Triterpenos Pentacíclicos , Temperatura , Triterpenos/farmacología , Ácido Betulínico
20.
Cardiovasc Diabetol ; 17(1): 26, 2018 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-29422093

RESUMEN

BACKGROUND: The extent of coronary collateral formation is a primary determinant of the severity of myocardial damage and mortality after coronary artery occlusion. Type 2 diabetes mellitus (T2DM) represents an important risk factor for impaired collateral vessel growth. However, the mechanism of reduced coronary collateralization in type 2 diabetic patients remains unclear. METHODS: With the reference to the recent researches, this review article describes the pathogenic effects of T2DM on collateral development and outlines possible clinical and biochemical markers associated with reduced coronary collateralization in type 2 diabetic patients with chronic total occlusion (CTO). RESULTS: Diffuse coronary atherosclerosis in T2DM reduces pressure gradient between collateral donor artery and collateral recipient one, limiting collateral vessel growth and function. An interaction between advanced glycation end-products and their receptor activates several intracellular signaling pathways, enhances oxidative stress and aggravates inflammatory process. Diabetic condition decreases pro-angiogenic factors especially vascular endothelial growth factor and other collateral vessel growth related parameters. Numerous clinical and biochemical factors that could possibly attenuate the development of coronary collaterals have been reported. Increased serum levels of glycated albumin, cystatin C, and adipokine C1q tumor necrosis factor related protein 1 were associated with poor coronary collateralization in type 2 diabetic patients with stable coronary artery disease and CTO. Diastolic blood pressure and stenosis severity of the predominant collateral donor artery also play a role in coronary collateral formation. CONCLUSIONS: T2DM impairs collateral vessel growth through multiple mechanisms involving arteriogenesis and angiogenesis, and coronary collateral formation in patients with T2DM and CTO is influenced by various clinical, biochemical and angiographic factors. This information provides insights into the understanding of coronary pathophysiology and searching for potential new therapeutic targets in T2DM.


Asunto(s)
Circulación Colateral , Enfermedad de la Arteria Coronaria/fisiopatología , Circulación Coronaria , Oclusión Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Neovascularización Patológica , Animales , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Oclusión Coronaria/sangre , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/epidemiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/diagnóstico por imagen , Angiopatías Diabéticas/epidemiología , Productos Finales de Glicación Avanzada/sangre , Humanos , Mediadores de Inflamación/sangre , Estrés Oxidativo , Pronóstico , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Factores de Riesgo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/sangre
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