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Background/Aims: Trials on the effects of cholecalciferol supplementation in type 2 diabetes with chronic kidney disease patients were underexplored. Therefore, the aim of this study was to investigate the effects of two different doses of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and metabolic parameters in vitamin D-deficient Korean diabetes patients with chronic kidney disease. Methods: 92 patients completed this study: the placebo group (A, n = 33), the oral cholecalciferol 1,000 IU/day group (B, n = 34), or the single 200,000 IU injection group (C, n = 25, equivalent to 2,000 IU/day). 52% of the patients had less than 60 mL/min/1.73m2 of glomerular filtration rates. Laboratory test and pulse wave velocity were performed before and after supplementation. Results: After 12 weeks, serum 25(OH)D concentrations of the patients who received vitamin D supplementation were significantly increased (A, -2.4 ± 1.2 ng/mL vs. B, 10.7 ± 1.2 ng/mL vs. C, 14.6 ± 1.7 ng/mL; p < 0.001). In addition, the lipid profiles in the vitamin D injection group (C) showed a significant decrease in triglyceride and a rise in HDL cholesterol. However, the other parameters showed no differences. Conclusions: Our data indicated that two different doses and routes of vitamin D administration significantly and safely increased serum 25(OH)D concentrations in vitamin D-deficient diabetes patients with comorbid chronic kidney disease. In the group that received the higher vitamin D dose, the lipid profiles showed significant improvement, but there were no beneficial effects on other metabolic parameters.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Deficiencia de Vitamina D , Colecalciferol , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos , Humanos , Análisis de la Onda del Pulso , Insuficiencia Renal Crónica/complicaciones , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
BACKGROUND AND AIMS: Coffee is known to have a beneficial effect on various liver diseases. The aim of this retrospective longitudinal study was to investigate an association between the amount of coffee consumption and the incidence of fatty liver disease in Korean adults. METHODS AND RESULTS: Data from a total of 91,436 male and female subjects with the mean follow-up period of 2.8 years were analyzed. The incidence of fatty liver was not associated with the amount of coffee consumption at baseline, but it was associated with the change in the amount of coffee consumption at the follow-up period. Multiple linear regression analyses showed that hazard ratios for incidence of fatty liver disease were significantly low in "increase" group comparing with "no change" group in fully adjusted model. When a subgroup analysis by gender was conducted, similar significant results were observed in male subjects, but not in females. CONCLUSIONS: The increment in the amount of coffee consumption is associated with the lower incidence of fatty liver in Korean men and suggests that increasing the coffee consumption may have a protective effect on fatty liver.
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Café , Hígado Graso/prevención & control , Adulto , Hígado Graso/diagnóstico , Hígado Graso/epidemiología , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Seúl/epidemiología , Factores SexualesRESUMEN
BACKGROUND: Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD). Recently, atherogenic index of plasma (AIP) has been proposed as a novel predictive marker for CVD, and few cross sectional studies have demonstrated a relationship between AIP and coronary artery disease. The present study investigated the association between AIP and the progression of coronary artery calcification (CAC) in Korean adults without CVD. METHODS: A total of 1124 participants who had undergone CAC measurement at least twice by multi-detector computed tomography (CT) at a health check-up center were enrolled. Their anthropometric measurements and various cardiovascular risk factors were assessed. AIP was defined as the base 10 logarithm of the ratio of the concentration of triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C). CAC progression was defined as either incident CAC in a CAC-free population at baseline, or an increase of ≥2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACS) in subjects with detectable CAC at baseline. RESULTS: CAC progression was observed in 290 subjects (25.8%) during the mean follow-up of 4.2 years. All subjects were stratified into three groups according to AIP. There were significant differences in cardiovascular parameters among groups at baseline. The follow-up CAC and the incidence of CAC progression increased gradually with rising AIP tertiles. In logistic regression analysis, the odds ratio for CAC progression was 2.27 when comparing the highest to the lowest tertile of AIP (95% CI: 1.61-3.19; P for trend < 0.01). However, this association was attenuated after adjustment for multiple risk factors (P for trend = 0.67). CONCLUSIONS: There is a significant correlation between AIP and the progression of CAC in subjects without CVD. Although AIP was not an independent predictor of CAC progression, AIP should be considered when estimating the current as well as future CVD risk, along with other traditional risk factors.
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Aterosclerosis/sangre , Enfermedad de la Arteria Coronaria/etiología , Pueblo Asiatico , Biomarcadores/sangre , Calcinosis/sangre , Calcinosis/diagnóstico por imagen , Calcinosis/etiología , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Estudios Retrospectivos , Triglicéridos/sangreRESUMEN
BACKGROUND: The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance. However, there are limited data regarding the association between the TyG index and arterial stiffness in adults. Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults. METHODS: A total of 3587 subjects were enrolled in this study. Anthropometric and cardiovascular risk factors were measured. The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. Arterial stiffness was determined by measuring baPWV. RESULTS: The subjects were stratified into four groups based on the TyG index. There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index. According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively. CONCLUSION: The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.
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Glucemia/análisis , Enfermedades Cardiovasculares/fisiopatología , Trastornos del Metabolismo de la Glucosa/sangre , Resistencia a la Insulina , Triglicéridos/sangre , Rigidez Vascular , Adulto , Índice Tobillo Braquial , Biomarcadores/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Femenino , Trastornos del Metabolismo de la Glucosa/diagnóstico , Trastornos del Metabolismo de la Glucosa/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Medición de Riesgo , Factores de Riesgo , Seúl/epidemiologíaRESUMEN
The use of fetal bovine serum (FBS) as a cryopreservation supplement is not suitable for the banking of mesenchymal stem cells (MSCs) due to the risk of transmission of disease as well as xenogeneic immune reactions in the transplanted host. Here, we investigated if human serum albumin (HSA), human serum (HS), or knockout serum replacement (KSR) can replace FBS for the cryopreservation of MSCs. In addition, we examined the characteristics of MSCs after multiple rounds of cryopreservation. Human adipose-derived stem cells (ASCs) cryopreserved with three FBS replacements, 9% HSA, 90% HS, or 90% KSR, in combination with 10% dimethyl sulfoxide (Me2SO) maintained stem cell properties including growth, immunophenotypes, gene expression patterns, and the potential to differentiate into adipogenic, osteogenic, and chondrogenic lineages, similar to ASCs frozen with FBS. Moreover, the immunophenotype, gene expression, and differentiation capabilities of ASCs were not altered by up to four freeze-thaw cycles. However, the performance of three or four freeze-thaw cycles significantly reduced the proliferation ability of ASCs, as indicated by the longer population doubling time and reduced colony-forming unit-fibroblast frequency. Together, our results suggest that HSA, HS, or KSR can replace FBS for the cryopreservation of ASCs, without altering their stemness, and should be processed with no more than two freeze-thaw cycles for clinical approaches.
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Criopreservación/métodos , Crioprotectores/farmacología , Células Madre Mesenquimatosas/citología , Adipocitos/citología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Dimetilsulfóxido/metabolismo , Congelación , Humanos , Suero , Albúmina Sérica Humana/farmacología , Bancos de TejidosRESUMEN
BACKGROUND: We investigated an association between the levels of plasma microRNA (miRNA)-21, -26a, and -29a-3p and treatment outcomes following transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). METHODS: A total of 198 patients with TACE-treated HCC were followed up for TACE refractoriness and liver transplantation (LT)-free survival. Pretreatment plasma miRNA-21, -26a, and -29a-3p levels were measured using quantitative real-time polymerase chain reaction. RESULTS: During the mean follow-up of 22.3 (range, 0.7-79) months, 118 (59.6%) patients exhibited TACE refractoriness. Multivariate analyses showed that expression of a specific combination of miRNAs (miRNA-21 ≥ 2.5, miRNA-26a ≥ 1.5, and miRNA-29a-3p < 0.4) was associated with early TACE refractoriness (within 1 year; hazard ratio [HR], 2.32; 95% confidence interval [CI], 1.08-4.99; P = 0.031) together with tumor size (HR, 4.62; 95% CI, 1.50-14.21; P = 0.008), and macrovascular invasion (HR, 3.80; 95% CI, 1.19-12.20; P = 0.025). However, miRNA-21, -26a, and -29a-3p levels were not significantly associated with overall TACE refractoriness or LT-free survival. Additionally, large tumor size and macrovascular invasion were common predictive factor of overall TACE refractoriness and survival. CONCLUSION: Combination of plasma miRNA-21, -26a, and -29a-3p expression could predict early TACE refractoriness in patients with TACE-treated HCC.
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Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , MicroARNs/sangre , Anciano , Área Bajo la Curva , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica , Doxorrubicina/administración & dosificación , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Tasa de SupervivenciaRESUMEN
BACKGROUND: The triglyceride glucose (TyG) index has been considered a simple surrogate marker of insulin resistance. However, few studies have investigated the relationship between the TyG index and coronary artery calcification (CAC). Thus, we investigated the relationship between the TyG index and CAC in healthy Korean adults. METHODS: In total, 4319 participants who underwent cardiac computed tomography (CT) in a health promotion center were enrolled. Anthropometric profiles and multiple cardiovascular risk factors were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. The CAC was measured using multidetector CT, and CAC presence was defined as an Agatston score of >0. RESULTS: All subjects were stratified into four groups based on their TyG indices. Significant differences were observed in cardiovascular parameters among the groups, and the prevalence of CAC significantly increased with increasing TyG index. In the logistic regression analysis after adjustment for multiple risk factors, the odds ratio for the prevalence of CAC, when comparing the highest and lowest quartiles of the TyG index was 1.95 (95% CI 1.23-3.11; P for trend = 0.01); the odds ratio for the prevalence of CAC, when comparing the highest and lowest quartiles of HOMA-IR was 1.64 (95% CI 1.12-2.40; P for trend = 0.04). In the receiver operating characteristics analysis, the TyG index was superior to HOMA-IR in predicting CAC. CONCLUSION: The TyG index is more independently associated with the presence of coronary artery atherosclerosis than is HOMA-IR in healthy Korean adults.
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Enfermedad de la Arteria Coronaria/sangre , Glucosa/metabolismo , Triglicéridos/sangre , Calcificación Vascular/sangre , Adulto , Anciano , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Calcificación Vascular/epidemiologíaRESUMEN
BACKGROUND: Although sorafenib is the only available drug with proven efficacy for patients with advanced hepatocellular carcinoma (HCC), the clinical efficacy of sorafenib is variable and unpredictable. The aim of the current study was to identify potential serum biomarkers predicting cancer progression and overall survival (OS) in patients with hepatitis B virus (HBV)-related advanced HCC treated with sorafenib. METHODS: Thirty-four patients with HBV-related advanced HCC (modified Union for International Cancer Control [UICC] stage IVa or IVb) treated with sorafenib for more than 4weeks were retrospectively enrolled. Using a Luminex 200 system, 11 cytokines including interleukin-17A (IL-17A) were measured in baseline serum samples prior to sorafenib administration. Several clinical factors and the serum concentrations of the 11 cytokines were analyzed using Cox regression analysis. RESULTS: In the analysis of progression-free survival (PFS), older age (year; hazard ratio [HR]=1.07; 95% confidence interval [CI]=1.00-1.15; P=0.046) and higher baseline serum IL-17A level (>1.94pg/mL; HR=19.96; 95% CI=3.32-119.86; P=0.001) were identified as significant risk factors for early progression with good predictive power (Harrell's C=0.817, standard error estimates (se)=0.085). In the analysis of OS, higher Child-Pugh score (>5; HR=2.35, 95% CI=1.09-5.10, P=0.030) and lower serum baseline fibroblast growth factor-2 level (≤20.57pg/mL; HR=3.24, 95% CI=1.22-8.60, P=0.018) were identified as negative predictive factors for OS, even though the model did not have significant predictive power (Harrell's C=0.634, se=0.062). CONCLUSION: A higher serum IL-17A level is a potential biomarker for predicting poor PFS in patients with HBV-related advanced HCC treated with sorafenib.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Hepatitis B/complicaciones , Interleucina-17/sangre , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Biomarcadores/sangre , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Estudios de Cohortes , Citocinas/sangre , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Niacinamida/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , SorafenibRESUMEN
BACKGROUND AND AIM: Circulating microRNA (miR)-122 has recently been investigated as a potential biomarker of various hepatic diseases, such as chronic hepatitis and hepatocellular carcinoma (HCC). We investigated the association between plasma miR-122 levels and the treatment outcomes following transarterial chemoembolization (TACE) in HCC patients. METHODS: We included 177 HCC patients treated with TACE in the study; TACE refractoriness and liver transplantation-free survival were evaluated during follow up. Pretreatment plasma miR-122 levels were assessed using quantitative real-time polymerase chain reaction. Relative quantification of miR-122 expression (fold change) was determined using the 2(-ΔΔCt) method. MiR-16 was used as an internal control for the normalization of miRNA data. RESULTS: During the mean follow up of 22.4 (range, 1-79) months, 112 (69.5%) patients exhibited TACE refractoriness. Multivariate analyses showed that tumor number (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.43-4.41; P = 0.001) and tumor size (HR, 2.65; 95% CI, 1.62-4.32; P = 0.000) can independently predict overall TACE refractoriness. High miR-122 expression (> 100) was associated with early TACE refractoriness (within 1 year; HR, 2.77; 95% CI, 1.12-6.86; P = 0.028), together with tumor number (HR, 22.73; 95% CI, 2.74-188.66; P = 0.004) and tumor size (HR, 4.90; 95% CI, 1.99-12.06; P = 0.001). Univariate analyses showed that high miR-122 expression tends to be associated with poor liver transplantation-free survival (HR, 1.42; 95% CI, 0.95-2.11; P = 0.085). However, it was statistically insignificant in multivariate analysis. CONCLUSION: High expression levels of plasma miR-122 are associated with early TACE refractoriness in HCC patients treated with TACE.
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Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Doxorrubicina/administración & dosificación , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , MicroARNs/sangre , Anciano , Aceite Etiodizado/administración & dosificación , Femenino , Estudios de Seguimiento , Esponja de Gelatina Absorbible/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Resultado del TratamientoRESUMEN
Although an association between serum ferritin and atherosclerosis has been suggested, limited epidemiologic data are available regarding the association between ferritin and arterial stiffness in healthy adults. A total of 2932 healthy subjects were enrolled in this study. Anthropometric and biochemical profiles including ferritin were measured. The arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV). Serum ferritin levels were classified into quartiles and baPWV values gradually increased with each ferritin quartile. Multiple regression analysis showed that ferritin levels were independently correlated with baPWV. After adjusting for multiple risk factors, as compared with the lowest quartile, the odds ratios for high baPWV (>75(th) percentile) were 1.15 (0.84-1.56), 1.37 (0.97-1.73), and 1.46 (1.29-2.17) among men (p for trend < 0.05) and 1.24 (0.87-1.79), 1.53 (1.09-2.16), and 1.80 (1.25-2.82) among women (p for trend < 0.05), for the second, third, and fourth quartiles of ferritin, respectively. In conclusion, serum ferritin levels are independently associated with arterial stiffness in healthy Korean adults.
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Pueblo Asiatico , Aterosclerosis/etnología , Ferritinas/sangre , Rigidez Vascular , Adulto , Índice Tobillo Braquial , Enfermedades Asintomáticas , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Aterosclerosis/fisiopatología , Biomarcadores/sangre , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Análisis de la Onda del Pulso , República de Corea , Factores de RiesgoRESUMEN
OBJECTIVE: Osteocalcin has been proposed to be a novel link between bone and energy metabolism. Previous studies showed its relations to exercise, body fat and glucose metabolism, but their interrelationship remains inconslusive. We evaluated the changes in osteocalcin level following 8-week exercise programme and assessed how they are related to concomitant changes in body fat composition, insulin resistance and various adipocytokines in a single centre, randomized and prospective design. STUDY DESIGN AND METHODS: A total of 39 young obese, otherwise healthy males were randomly assigned to control (n = 10) and exercise (n = 29) groups. Subjects in Exercise group were on 8-week supervised exercise training programme of four sessions per week. Body fat compositions were analysed using whole body bone mineral density, various metabolic parameters, osteocalcin and adipocytokines were assessed from fasting blood samples before and after 8-week exercise programme. RESULTS: Body fat reduction following exercise significantly increased serum total (1·51 ± 0·36 vs 1·69 ± 0·39 mmol/l, P = 0·01, baseline vs postexercise) and undercarboxylated osteocalcin level (0·44 ± 0·14 vs 0·64 ± 0·26 mmol/l, P < 0·01), and the increase in osteocalcin was in negative correlations with changes in body weight, BMI and body fat percentage as well as HOMA-IR and leptin (all P < 0·05). The changes in osteocalcin and leptin were not independent predictors of changes in insulin resistance and osteocalcin, respectively. CONCLUSIONS: In a physiological axis of bone-fat-energy metabolism, exercise-induced body fat reduction and improved insulin sensitivity were accompanied by an increase in serum osteocalcin and leptin levels, but other factors also seem to be involved in this interrelationship.
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Adipoquinas/sangre , Ejercicio Físico , Resistencia a la Insulina , Obesidad/sangre , Osteocalcina/sangre , Adiposidad , Adulto , Índice de Masa Corporal , Estudios Transversales , Metabolismo Energético , Humanos , Leptina/sangre , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
Currently, there are limited ways to preserve or recover insulin secretory capacity in human pancreas. We evaluated the efficacy of cell therapy using insulin-secreting cells differentiated from human eyelid adipose tissue-derived stem cells (hEAs) into type 2 diabetes mice. After differentiating hEAs into insulin-secreting cells (hEA-ISCs) in vitro, cells were transplanted into a type 2 diabetes mouse model. Serum levels of glucose, insulin and c-peptide were measured, and changes of metabolism and inflammation were assessed in mice that received undifferentiated hEAs (UDC group), differentiated hEA-ISCs (DC group), or sham operation (sham group). Human gene expression and immunohistochemical analysis were done. DC group mice showed improved glucose level, and survival up to 60 days compared to those of UDC and sham group. Significantly increased levels of human insulin and c-peptide were detected in sera of DC mice. RT-PCR and immunohistochemical analysis showed human gene expression and the presence of human cells in kidneys of DC mice. When compared to sham mice, DC mice exhibited lower levels of IL-6, triglyceride and free fatty acids as the control mice. Transplantation of hEA-ISCs lowered blood glucose level in type 2 diabetes mice by increasing circulating insulin level, and ameliorating metabolic parameters including IL-6.
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Adipocitos/patología , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirugía , Células Secretoras de Insulina/patología , Células Secretoras de Insulina/trasplante , Células Madre/patología , Animales , Diferenciación Celular , Células Cultivadas , Femenino , Humanos , Insulina/sangre , Ratones , Ratones Endogámicos C57BL , Resultado del TratamientoRESUMEN
To investigate the effect of natural pyrazinamidase (PncA) mutations on protein function, we analyzed expression and PncA activity of eight pncA point mutants identified in nineteen pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates. Among them, two mutants (Y99D and T135P) showed high expression level and solubility comparable to those of the wild-type PncA protein, two (K48E and G97D) displayed low expression level and solubility, and four (C14R, H51P, W68S, and A146V) were insoluble. Interestingly, when possible structural effects of these mutations were predicted by the CUPSAT program based on the proposed three-dimensional structure of M. tuberculosis PncA, only two highly soluble mutant proteins (Y99D and T135P) were predicted to be stabilizing and have favorable torsion angles. However, the others exhibiting either low solubility or precipitation were foreseen to be destabilizing and/or have unfavorable torsion angles, suggesting that the alterations could interfere with proper protein folding, thereby decreasing or depleting protein solubility. A PncA activity assay demonstrated that two mutants (G97D and T135P) showed virtually no activity, but two other mutants (K48E and Y99D) exhibited wild-type activity, indicating that the PncA residues (Cys14, His51, Trp68, Gly97, Thr135, and Ala146) may be important for PncA activity and/or proper protein folding.
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Amidohidrolasas/metabolismo , Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis/enzimología , Mutación Puntual , Pirazinamida/farmacología , Amidohidrolasas/química , Amidohidrolasas/genética , Perfilación de la Expresión Génica , Humanos , Corea (Geográfico) , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutación Missense , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Conformación Proteica , Estabilidad Proteica , Tuberculosis/microbiologíaRESUMEN
OBJECTIVE: The aim of this study was to investigate the role of the follistatin-like 1 (Fstl1) and disco-interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity. METHODS: Twenty-nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3-L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise-induced lipolysis was examined. RESULTS: Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3-L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise. CONCLUSIONS: Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a-mediated lipolytic effects in adipocytes.
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Proteínas Relacionadas con la Folistatina , Folistatina , Humanos , Masculino , GMP Cíclico/metabolismo , Folistatina/metabolismo , Proteínas Relacionadas con la Folistatina/genética , Proteínas Relacionadas con la Folistatina/metabolismo , Glicerol/metabolismo , Movilización Lipídica , Lipólisis/fisiología , Mioquinas , Esterol Esterasa/metabolismoRESUMEN
OBJECTIVES: Musclin, recently identified as a myokine, has been recognized for its physiological significance in potentiating the functional properties of natrieutic peptides (NPs) through competitive inhibition of their clearance receptor, natrieutic peptide receptor C (NPR-C). This study, for the first time in the literature, investigated the dynamic response of musclin during and after aerobic exercise in humans, exploring its potential as a myokine and its interaction with NPs and NPR-C in the context of exercise-induced metabolic responses. METHODS: Twenty-one inactive young males participated, and we assessed changes in serum levels of musclin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), epinephrine (Epi), and glycerol as an indicative of lipid mobilization, during and after moderate-intensity aerobic exercise. Furthermore, we evaluated the gene expression of NPR-C in subcutaneous fat biopsies. RESULTS: Serum musclin levels increased significantly during aerobic exercise, followed by a decline during recovery, remaining elevated compared to baseline. Significant correlations were found between musclin responses and lean body mass (LBM), indicating its regulation by skeletal muscle mass and exercise. Exercise-induced changes in musclin positively correlated with those of ANP, potentially preventing ANP degradation. Additionally, a potential interplay between NPR-C expression and musclin dynamics on ANP was suggested. However, musclin's influence on lipid mobilization was not predominant when considering other lipolytic factors during exercise. DISCUSSION: Musclin's classification as a myokine is supported by its response to aerobic exercise and its association with LBM. Additionally, its interactions with NPR-C and NPs suggest its physiological relevance and potential clinical implications.
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BACKGROUND: The prevalence of coronary artery stenosis (CAS) at the initiation of renal replacement therapy (RRT) in chronic kidney disease (CKD) patients has not been fully elucidated. Although coronary angiography is the gold standard in diagnosing CAS its invasiveness and economic burden lead to searching for a noninvasive alternative method. In this study, we evaluated the prevalence of CAS by multidetector row computed tomography (MDCT) and related risk factor to articulate the usefulness of MDCT. METHOD: Seventy-four asymptomatic CKD patients who began dialysis were evaluated with echocardiography and MDCT. The patients were stratified into two groups according to CAS and coronary artery calcification score (CACS) by MDCT to detect silent CAS and evaluate its predictability for cardiac events. RESULTS: CAS was seen in 24 (32.4%) of 74 asymptomatic CKD patients on MDCT. Both groups showed increasing frequencies of CAS with age (P < 0.01), presence of diabetes (P < 0.05), uric acid level (P < 0.01), and calcium score (P < 0.01). Multiple regression analysis revealed that age and uric acid level were independent risk factors for CAS and high CACS in asymptomatic CKD patients at the initiation of dialysis. Patients with both CAS and high CACS were presented with higher cardiac events rates compared to those without any of them. In Cox regression model, age and the presence of CAS and high CACS on MDCT were an independent risk factor for cardiac events in these patients. CONCLUSION: We showed that CAS was highly seen in asymptomatic CKD patients starting dialysis. Moreover, both high CACS and CAS on MDCT might predict cardiac events in these patients and MDCT can be a useful screening tool for evaluating coronary artery disease and predicting cardiovascular mortality noninvasively.
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Estenosis Coronaria/diagnóstico por imagen , Fallo Renal Crónico/complicaciones , Terapia de Reemplazo Renal , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Estenosis Coronaria/complicaciones , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana EdadRESUMEN
The plasma atherogenic index (AIP) has been suggested as a useful independent predictor of cardiovascular diseases (CVDs) in high CV risk patients. We investigated the association between AIP and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) in healthy adults. A total of 3468 healthy subjects without any metabolic or CV diseases were enrolled. Anthropometric and CV risk factors were measured. The AIP was defined as the base 10 logarithm of the ratio of the concentration of triglycerides to high-density lipoprotein-cholesterol. Subjects were classified into AIP quartiles. There were gradual deteriorations in metabolic parameters and increase in baPWV across the increasing AIP quartiles. In a fully adjusted analysis, compared with Q1 (lowest quartile) group, the odds ratio (95% confidence interval) for increased baPWV was higher in Q2 1.51, Q3 1.64, and Q4 (highest quartile) 2.77 among men, and Q2 1.09, Q3 1.55, and Q4 1.83 among women (all P trendâ <0â.05). There was a strong association between AIP and baPWV, and a higher AIP was an independent predictor of increased arterial stiffness in healthy Korean men and women. The AIP may be a simple screening tool for subclinical atherosclerosis.
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Enfermedades Cardiovasculares , Rigidez Vascular , Adulto , Índice Tobillo Braquial , HDL-Colesterol , Femenino , Humanos , Masculino , Análisis de la Onda del Pulso , República de Corea/epidemiología , Factores de RiesgoRESUMEN
PURPOSE: Oxidative stress plays an important role in the pathogenesis of chronic metabolic diseases. This study investigated the effect of the antioxidant-rich dietary intervention on oxidative stress, metabolic parameters, and arterial stiffness in elderly Koreans with metabolic syndrome (MetS). MATERIALS AND METHODS: Thirty-one subjects with MetS were enrolled and randomly divided into dietary intervention group and control group. Subjects in the intervention group received three meal boxes prepared with antioxidant-rich ingredients every day for 4 weeks, and subjects in the control group maintained their usual diets. Anthropometric and various biochemical parameters related to oxidative stress, inflammation, and MetS were assessed. Brachial-ankle pulse wave velocity (baPWV) and fat measurement using computed tomography were also conducted before and after 4 weeks. RESULTS: There were significant differences in waist circumference, visceral to subcutaneous fat ratio, lipid peroxidation, oxidized low density lipoprotein (oxLDL), systolic and diastolic blood pressure, lipid parameters, advanced glycation end products, and baPWV between before and after the study in the experimental group (all p<0.05). Significant inter-group differences were observed between the experimental and control group in terms of the differences in body mass index, waist circumference, oxygen radical absorbance capacity, protein carboxylation, lipid peroxidation, oxLDL, blood pressure, lipid parameters, and baPWV between before and after the study (all p<0.05). CONCLUSION: Antioxidant-rich dietary intervention for a 4-week period ameliorated the state of oxidative stress and improved the components of MetS including central obesity, dyslipidemia, hypertension, and arterial stiffness in elderly Koreans with MetS.
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Hipertensión , Síndrome Metabólico , Rigidez Vascular , Anciano , Índice Tobillo Braquial , Antioxidantes , Presión Sanguínea , Humanos , Análisis de la Onda del Pulso , República de CoreaRESUMEN
BACKGROUND: Several experimental studies have suggested beneficial effects of Ceriporia lacerata on glucose metabolism. However, there has been no human study assessing the effects of C. lacerata on glucose metabolism. Therefore, we investigated whether C. lacerata improves glucose control and insulin resistance in type 2 diabetes patients. METHODS: Ninety patients diagnosed with type 2 diabetes (T2DM) for more than 6 months were enrolled. Subjects were randomly divided into placebo (n = 45) or C. lacerata (n = 45) groups and then assigned to take placebo or C. lacerata capsules (500 mg/capsule) for a 12-week intervention period. Biochemical markers, including fasting glucose, 2-hour postprandial plasma glucose, and lipid profile levels, as well as insulin, c-peptide, and Hba1c, were measured. Furthermore, insulin sensitivity indices, such as HOMA-IR, HOMA-beta, and QUICKI, were assessed before and after the 12-week administration. RESULTS: Eighty-four patients completed the study. There were no significant differences in fasting, postprandial glucose, HbA1c, or lipid parameters. HOMA-IR and QUICKI indices were improved at week 12 in the C. lacerata group, especially in subjects with HOMA-IR of 1.8 or more (p < 0.05). Fasting, postprandial c-peptide, and insulin levels decreased at week 12 in the C. lacerata group (p < 0.05). These significant differences were not observed in the placebo group. CONCLUSION: Twelve-week administration of C. lacerata in T2DM patients resulted in significant improvement in insulin resistance, especially in those with lower insulin sensitivity. A larger population study with a longer follow-up period and an effort to elucidate the mechanism is warranted to further assess the effects of C. lacerata on T2DM patients.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Resistencia a la Insulina/fisiología , Extractos Vegetales/farmacología , Polyporales/metabolismo , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Extractos Vegetales/metabolismo , Extractos Vegetales/uso terapéuticoRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM. METHODS: A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD. RESULTS: Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters. CONCLUSION: The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinical practice.