RESUMEN
Ischemiaâreperfusion (I/R) is a common complication in the clinical treatment of acute myocardial infarction (MI), in which cardiomyocytes play a pivotal role in the recovery of cardiac function after reperfusion injury. The expression of numerous circular ribonucleic acids (circRNAs) is disrupted in I/R-induced cardiac damage, but the potential role of circRNAs in I/R damage has not been fully elucidated. The purpose of the present study was to clarify the biological action and molecular mechanism of circRNA 002166 (also termed circCL2L13) in postmyocardial I/R. Oxygen-glucose deprivation/reoxygenation (OGD/R) in an in vivo model was performed to simulate I/R damage. real-time polymerase chain reaction analysis was also conducted to evaluate the relationships of the SOD1, SOD2, NRF2, HO1 and GPX4 indicators with oxidative stress injury. TUNEL immunofluorescence was used to evaluate the degree of cardiomyocyte apoptosis in the different treatment groups. The circBCL2L13 level was markedly upregulated in myocardial tissues from a mouse I/R model. Overexpression of circBCL2L13 markedly attenuated the expression of oxidative stress-related genes and apoptosis in OGD/R-induced cardiomyocytes. A mechanistic study revealed that circBCL2L13 functions as a ceRNA for miR-1246 and modulates paternally expressed gene 3 (PEG3). Eventually, circBCL2L13 was proven to regulate PEG3 by targeting miR-1246, thereby protecting against OGD/R-induced cardiomyocyte oxidative damage and apoptosis. In conclusion, our study confirmed that the circBCL2L13/miR-1246/PEG3 axis suppressed the progression of OGD/R injury in cardiomyocytes, which might lead to new therapeutic strategies for cardiac I/R injury.
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Apoptosis , MicroARNs , Estrés Oxidativo , ARN Circular , Daño por Reperfusión , Animales , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Daño por Reperfusión/metabolismo , ARN Circular/genética , ARN Circular/metabolismoRESUMEN
BACKGROUND AND AIMS: Conflicting evidence exists regarding the association between green tea consumption and the risk of coronary heart disease (CHD). We performed a meta-analysis to determine whether an association exists between them in cohort studies. METHODS AND RESULTS: We searched the PubMed and EMBASE databases for studies conducted until September 2022. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association were included. Study-specific risk estimates were combined using a random-effects model. A total of seven studies, with 9211 CHD cases among 772,922 participants, were included. We observed a nonlinear association between green tea consumption and the risk of CHD (P for nonlinearity = 0.0009). Compared with nonconsumers, the RRs (95% CI) of CHD across levels of green tea consumption were 0.89 (0.83, 0.96) for 1 cup/day (1 cup = 300 ml), 0.84 (0.77, 0.93) for 2 cups/day, 0.85 (0.77, 0.92) for 3 cups/day, 0.88 (0.81, 0.96) for 4 cups/day, and 0.92 (0.82, 1.04) for 5 cups/day. CONCLUSIONS: This updated meta-analysis of studies from East Asia suggests that green tea consumption may be associated with a reduced risk of CHD, especially among those with low-to-moderate consumption. Additional cohorts are still needed before we could draw a definitive conclusion. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022357687.
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Enfermedad Coronaria , Té , Humanos , Té/efectos adversos , Estudios Prospectivos , Riesgo , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/prevención & control , Extractos Vegetales , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: Prospective cohorts are inconsistent regarding the association between dietary calcium intake and the risk of stroke. The aim was to perform a meta-analysis to determine whether an association exists between them in cohort studies. METHODS AND RESULTS: Relevant studies were identified by searching PubMed, EMBASE and Web of Science databases that published before December 2022. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association were included. Study-specific risk estimates were combined by using a random effects model. Eighteen prospective studies, including 19,557 stroke cases among 882,181 participants, were pooled in the meta-analysis. We observed a nonlinear association between calcium intake and risk of stroke (Pnonlinearity < 0.003). Compared with the lowest value of zero assumed as the reference, the RRs (95% CI) of stroke across levels of calcium intake were 0.95 (0.92, 0.98) for 200 mg/day, 0.94 (0.90, 0.98) for 300 mg/day, 0.95 (0.90, 0.99) for 500 mg/day, 0.98 (0.93, 1.03) for 700 mg/day, and 1.04 (0.97, 1.11) for 1000 mg/day. The stratified analyses by geographic region showed nonlinear associations and indicated that the protective effect was observed in Asian countries (Pnonlinearity = 0.001) but not in non-Asian regions (Pnonlinearity = 0.047). CONCLUSION: This meta-analysis suggests that dietary calcium intake might play an effective role in the prevention of stroke, especially in Asian countries. Future research among Asia population should attempt to establish whether this association is causal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022357710.
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Calcio de la Dieta , Accidente Cerebrovascular , Humanos , Estudios Prospectivos , Factores de Riesgo , Calcio de la Dieta/efectos adversos , Calcio , Estudios de Cohortes , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
BACKGROUND/AIMS: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, has been shown to prevent cardiovascular diseases. Previously, Matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1) and toll-like receptor 4 (TLR4) were confirmed to play an important role in atherosclerosis and plaque instability. Both TLR4 and its negative regulator, Toll-interacting protein (Tollip), could be mediated by EGCG. The present study aimed to examine the effect of physiological concentration of EGCG (1 µM) on the expression of MMP-9 and MCP-1 in lipopolysaccharide (LPS)-induced macrophages and the potential mechanisms underlying its actions. METHODS: The RAW264.7 cell line was used. Western blot was used to determine MCP-1, TLR4, Tollip, Mitogen-activated protein kinase (MAPK) and Nuclear factor-κB (NF-κB) protein expression. MMP-9 activity was assayed by gelatine zymography. The mRNA expression of MMP-9 and MCP-1 was measured by realtime polymerase chain reaction (RT-PCR). RESULTS: EGCG (1 µM) significantly suppressed the expression of MMP-9 and MCP-1 and inhibited MAPK and NF-κB in LPS-induced macrophages but was blocked by Tollip silencing. The expression of LPS-induced MMP-9 and MCP-1 and the phosphorylation of the ERK1/2, P38 and NF-κB pathway proteins decreased after TLR4 siRNA treatment. Furthermore, EGCG mediated TLR4 and Tollip expression through binding to 67-kDa laminin receptor (67LR). CONCLUSION: The results of our study suggested that EGCG (1 µM) suppresses the TLR4/MAPK/NF-κB signalling pathway, decreases the expression of the plaque instability-mediating cytokines MMP-9 and MCP-1, and might prove to be effective in stabilizing atherosclerotic plaque.
Asunto(s)
Catequina/análogos & derivados , Quimiocina CCL2/metabolismo , Lipopolisacáridos/toxicidad , Receptores de Laminina/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Catequina/farmacología , Quimiocina CCL2/genética , Regulación hacia Abajo/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Células RAW 264.7 , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND/AIMS: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. METHODS: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. RESULTS: We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. CONCLUSION: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.
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Basigina/metabolismo , Catequina/análogos & derivados , Macrófagos/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Receptores de Laminina/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Catequina/química , Catequina/farmacología , Muerte Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
AIMS: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, displays a variety of pharmacological properties and recently received attention as a prospective dietary intervention in cardiovascular diseases (CVD). This study was conducted to test the hypothesis that EGCG was able to inhibit tumor necrosis factor-α (TNF-α)-induced production of monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) and investigated the underlying molecular mechanisms. METHODS: The inhibitory effect of EGCG on TNF-α-induced expression of MCP-1 was measured using ELISA and RT-qPCR. The effect of EGCG on TNF-α-induced nuclear factor-kappa B (NF-κB) activation was investigated by western blot and luciferase assays. Monocyte adhesion assay was detected by microscope. RESULTS: EGCG significantly suppressed the TNF-α-induced protein and mRNA expression of MCP-1. Investigation of the mechanism suggested that EGCG suppressed the TNF-α-mediated NF-κB activation. In addition, the 67-kD laminin receptor (67LR) was involved in EGCG-mediated suppression of MCP-1 generation. Furthermore, EGCG potently inhibited monocyte adhesion to activated HUVECs. CONCLUSION: EGCG suppresses TNF-α-induced MCP-1 expression in HUVECs. This effect was mediated by 67LR and was via the inhibition of NF-κB activation. Our results demonstrated that EGCG might be a possible medicine for CVD prevention and treatment.
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Catequina/análogos & derivados , Quimiocina CCL2/biosíntesis , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Té/química , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Catequina/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Quimiocina CCL2/genética , Relación Dosis-Respuesta a Droga , Humanos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
OBJECTIVE: To examine the influence of walking at different times of day on lipids and inflammatory markers in sedentary patients with coronary artery disease (CAD). METHODS: A total of 330 patients recruited from Nanjing between September 2011 and November 2012 were randomly assigned to a control group (n=110), morning (n=110) or evening walking group (n=110). Both the walking groups were asked to walk 30 min/day or more on at least 5 days/week either in the morning or evening for 12 weeks. Lipids and inflammatory markers were measured before and after exercise intervention. RESULTS: Compared with baseline, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were improved in all groups. Significances were shown in the changes of fibrinogen, high sensitivity C-reactive protein (hsCRP), white blood cell (WBC) count, TC, triglycerides, LDL-C, lipoprotein(a) between groups. The evening walking group had a larger decrease in fibrinogen (0.16 ± 0.19 g/L, P<0.001), hsCRP (1.16 ± 1.07 mg/L, P<0.001), WBC count (0.76 ± 1.53·10(9)/L, P=0.004) and LDL-C (0.34 ± 0.31 mmol/L, P<0.001) than the other two groups. CONCLUSIONS: Our walking program successfully resulted in a favorable change in lipids and inflammatory markers. Patients in the evening walking group gained more benefits than those walking in the morning walking group. NCT01887093.
Asunto(s)
Biomarcadores/sangre , Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Inflamación/sangre , Conducta Sedentaria , Caminata/fisiología , Aceleración , Adulto , Anciano , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , China , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/prevención & control , Femenino , Procesos de Grupo , Promoción de la Salud/métodos , Humanos , Masculino , Equivalente Metabólico , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: Exercise leads to a lower risk of coronary artery disease (CAD). However, whether time of day physical exercise has effects on CAD is still unclear. The present study is to investigate the relationship between time of day physical exercise and angiography determined CAD in a Chinese population. SUBJECTS: A total of 1,129 consecutive participants who underwent coronary angiography for the first time were enrolled in our study. Participants were divided into non-CAD group and CAD group according to the result of coronary angiography. We used a predesigned questionnaire-the work-related activity, leisure-time activity, and physical exercise information were recorded in the form of self-reporting. RESULTS: Doing physical exercise was associated with a reduced risk of CAD, after adjusting the established and potential confounders, with an adjusted odds ratio (OR) of 0.48 (95% CI, 0.35-0.67) compared with those who did not any physical exercise. Moreover, the risk of CAD could linearly decrease with increase of intensity, duration and frequency of exercise. Further stratification analysis revealed that the protective effects of exercise were more significant in the afternoon and evening group than in the morning and forenoon group. The adjusted ORs of doing physical exercise in morning, forenoon, afternoon, and evening groups were 0.53 (0.36-0.78), 0.51(0.27-0.96), 0.46(0.25-0.85), 0.43(0.28-0.66), respectively, compared with nonexerciser (p < .05). CONCLUSIONS: Doing physical exercise can decrease the risk of CAD, and exercising in the afternoon or evening may have more significant effects on the prevention of CAD than in other time of day.
Asunto(s)
Enfermedad de la Arteria Coronaria/prevención & control , Ejercicio Físico , Anciano , China , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Autoinforme , Encuestas y CuestionariosRESUMEN
Sepsis-induced myocardial dysfunction (SIMD) has become one of the most lethal complications of sepsis, while the treatment was limited by a shortage of pertinent drugs. Epigallocatechin-3-gallate (EGCG) is the highest content of active substances in green tea, and its application in cardiovascular diseases has broad prospects. This study was conducted to test the hypothesis that EGCG was able to inhibit lipopolysaccharide (LPS) induced myocardial dysfunction and investigate the underlying molecular mechanisms. The cardiac systolic function was assessed by echocardiography. The cardiomyocyte apoptosis was determined by TUNEL staining. The expression of inflammatory factors and apoptosis-related protein, cardiac markers were examined by Western Blot and qRT-PCR. EGCG effectively improve LPS-induced cardiac function damage, enhance left ventricular systolic function, and restore myocardial cell vitality. It can effectively inhibit the upregulation of TLR4 expression induced by LPS and inhibit IκB α/NF- κB/p65 signaling pathway, thereby inhibiting cardiomyocyte apoptosis and improving myocarditis. In conclusion, EGCG protects against SIMD through anti-inflammatory and anti-apoptosis effects; it was mediated by the inhibition of the TLR4/NF-κB signal pathway. Our results demonstrated that EGCG might be a possible medicine for SIMD prevention and treatment.
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Background: Ventricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce. Methods: This study (symptom-to-balloon time and VEntricular aRrhYthmias in patients with STEMI, VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %). Results: A total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group. Conclusions: S2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h.
RESUMEN
OBJECTIVES: Epidemiologic studies are inconsistent regarding the association between green tea consumption and the risk of stroke. We performed a meta-analysis to determine whether an association exists between them in cohort studies. METHODS: We searched the PubMed and Embase databases for studies conducted from 1966 through September 2022. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence interval (CI)s for the association were included. Study-specific risk estimates were combined by using a random-effects model. RESULTS: A total of five studies, with 11 421 stroke cases among 645 393 participants, were included in the meta-analysis. The summary RR indicated a significant association between highest green tea consumption and reduced risk of stroke (summary RR: 0.74; 95% CI, 0.66-0.83). In the dose-response analysis, we observed a nonlinear association between green tea consumption and the risk of stroke (P for nonlinearityâ¯=â¯0.0000). Compared with non-consumers, the RRs (95% CI) of stroke across levels of green tea consumption were 0.91 (0.89-0.94) for 150 mL/d, 0.84 (0.80-0.89) for 300 mL/d, 0.79 (0.74-0.84) for 500 mL/d, 0.77 (0.72-0.82) for 900 mL/d, and 0.84 (0.77-0.91) for 1500 mL/d. CONCLUSIONS: This meta-analysis suggests that green tea consumption is inversely associated with the risk of stroke, especially among those with moderate consumption. Our results support recommendations for green tea consumption to the primary prevention of stroke.
Asunto(s)
Accidente Cerebrovascular , Té , Humanos , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Riesgo , Extractos Vegetales , Factores de RiesgoRESUMEN
BACKGROUND: Tirofiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist used widely in patients subjected to percutaneous coronary intervention. While the usage of tirofiban sets an important clinical benefit, severe thrombocytopenia can occur with use of this agent. CASE PRESENTATION: A 76-year-old Chinese man was admitted with 1-month history of sudden onset of chest tightness. He was diagnosed as having subacute inferior myocardial infarction, and percutaneous coronary intervention was performed. After the procedure, patient received tirofiban at 0.15 µg/kg/minute for 4 h. A blood sample was obtained for a complete blood count; severe thrombocytopenia was reported according to routine orders at our hospital. All antiplatelet drugs including tirofiban, aspirin, and clopidogrel were immediately discontinued. The patient received platelet transfusions and was treated with immunoglobulin G. Two days later, the patient's platelet count had increased to 75 × 109/L. There was a significant improvement after day 5, and the platelet count was 112 × 109/L. Seven days after the acute thrombocytopenia, he was discharged with normal platelet count. CONCLUSIONS: Clinicians should be particularly aware of tirofiban-induced thrombocytopenia in routine practice.
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Angioplastia Coronaria con Balón , Intervención Coronaria Percutánea , Trombocitopenia , Masculino , Humanos , Anciano , Tirofibán/efectos adversos , Tirosina/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Trombocitopenia/terapia , Intervención Coronaria Percutánea/efectos adversosRESUMEN
Cadmium (Cd) is a toxic heavy metal linked to an increased risk of cardiovascular disease (CVD). But the relationship between urinary Cd (U-Cd) and electrocardiographic subclinical myocardial injury (SC-MI) in older people is unclear. This study evaluated the connection between U-Cd and SC-MI in people who did not have CVD. The study involved 4269 participants from the National Health and Nutrition Examination Survey III(NHANES III) aged ≥ 50 years and had no history of CVD. The relationship between U-Cd and cardiac infarction/injury score (CIIS) was assessed by multivariable linear regression. Whether U-Cd and SC-MI were correlated was determined by multivariate logistic regression, restricted cubic spline, and subgroup analysis. There was a significant association between U-Cd and CIIS (ß, 1.04, 95% confidence interval (CI): 0.39-1.69; P = 0.003) in the highest quartile and fully adjusted model. After adjusting for relevant confounders, multivariable logistic regression showed that participants in the highest quartile of U-Cd had a greater chance of having SC-MI than those in the first ( OR (95% CI), 1.37(1.13,1.66), P for trend = 0.003), and this relationship was especially strong among hypertensive participants. And a positive linear correlation between U-Cd and the prevalence of SC-MI was shown by restricted cubic spline analysis. U-Cd may be a novel risk element for SC-MI because it is independently and linearly linked to CIIS and SC-MI.
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Enfermedades Cardiovasculares , Hipertensión , Infarto del Miocardio , Humanos , Anciano , Enfermedades Cardiovasculares/epidemiología , Cadmio , Encuestas Nutricionales , Infarto del Miocardio/epidemiología , Hipertensión/epidemiologíaRESUMEN
Visfatin, a pro-inflammatory cytokine predominantly released from leucocytes, is correlated with coronary artery disease (CAD). We have previously reported that the -1535C>T polymorphism (rs1330082), which located on the promoter region of visfatin, was associated with decreased risk of CAD. Here, we investigated the underlying mechanism by which this polymorphism affects the genetic susceptibility to CAD. The difference of the promoter activities between -1535T variant and -1535C allele was tested by luciferase reporter gene assay. The difference of transcription factor binding activities between T and C allele was evaluated by electrophoretic mobility shift assay. In reporter gene assay, we showed that the T variant had a significantly reduced transcriptional activity compared with the C allele. The T-variant significantly attenuated the promoter binding affinity to nuclear transcription factors and this effect became much obvious after treatment with TNF-α. Moreover, competition experiment revealed that the retarded complex formed by T-1535- or C-1535-probe binding to nuclear extracts was nearly completely inhibited by unlabeled activator protein-1 (AP-1) specific probe, indicating that AP-1 might be the target nuclear effector. Taken together, our data provided potential mechanistic link between the visfatin -1535C>T polymorphism and reduced CAD risk.
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Enfermedad de la Arteria Coronaria/genética , Citocinas/genética , Nicotinamida Fosforribosiltransferasa/genética , Polimorfismo de Nucleótido Simple , Sitios de Unión , Enfermedad de la Arteria Coronaria/metabolismo , Citocinas/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Genes Reporteros , Predisposición Genética a la Enfermedad , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Interleucina-6/metabolismo , Nicotinamida Fosforribosiltransferasa/metabolismo , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , Factor de Transcripción AP-1/metabolismo , Transcripción Genética , Transfección , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Hyperlipidemia plays a crucial role in the development and progression of coronary artery disease (CAD). Recent studies have identified that microRNAs (miRNAs) are important regulators of lipid metabolism, but little is known about the circulating levels of lipometabolism-related miRNAs and their relationship with the presence of CAD in patients with hyperlipidemia. METHODS: In the present study, we enrolled a total of 255 hyperlipidemia patients with or without CAD and 100 controls with normal blood lipids. The plasma levels of four known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol were determined. Furthermore, the severity of CAD was assessed with the Gensini score system based on the degree of luminal narrowing and its geographic importance. RESULTS: Our results revealed for the first time that plasma levels of miR-122 and miR-370 were significantly increased in hyperlipidemia patients compared with controls, and the levels of miR-122 and miR-370 were positively correlated with TC, TG, and LDL-C levels in both hyperlipidemia patients and controls. Multiple logistic regression analysis demonstrated that the increased levels of miR-122 and miR-370 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, miR-122 and miR-370 levels were positively correlated with the severity of CAD quantified by the Gensini score. However, both miR-33a and miR-33b were undetectable in plasma. CONCLUSIONS: Our results suggest that increased plasma levels of miR-122 and miR-370 might be associated with the presence as well as the severity of CAD in hyperlipidemia patients.
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Enfermedad de la Arteria Coronaria/sangre , Hiperlipidemias/sangre , Metabolismo de los Lípidos , MicroARNs/sangre , Anciano , Estudios de Casos y Controles , Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/patología , Femenino , Humanos , Hiperlipidemias/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Triglicéridos/sangreRESUMEN
Background: Children and adolescents increasingly commonly suffer from obesity and headache. It has been confirmed that there is an association between obesity and headache in adults; however, evidence of such an association in paediatric populations is still controversial. Therefore, this study examined the relationship between obesity and headache among children and adolescents in the US. Methods: The cross-sectional data of 3948 participants were obtained from the National Health and Nutrition Examination Survey 1999-2004. Weighted logistic regression models were applied to investigate the association between obesity and headache. Subgroup analysis stratified by sex and age was performed to explore the potential difference in the association of paediatric obesity with headache. The performance of paediatric obesity on headache was assessed by receiver operating characteristic (ROC) curve. Results: The present study involved 3948 participants, of whom 713 (18.1%) had headache. Compared to those without headache, participants with headache tended to be girls and adolescents, have less calcium intake, and have higher levels of body mass index (BMI), C-reactive protein (CRP), serum ferritin and triglycerides (TGs) (all P < 0.05). After fully adjusting for potential confounders, the ORs with 95% CIs for headache were 1.03 (0.58-1.54) and 1.25 (0.68-2.30) for overweight and obese participants in comparison with normal-weight controls, respectively, implying no association of paediatric obesity with headache independent of other potential confounding factors. In addition, although higher odds of headache were noted in girls and adolescents (aged 10-17 years), no statistically significant difference was found across any subgroups. The area under the ROC (AUC) of paediatric obesity on headache was 0.634. Conclusions: In summary, our study indicated that obesity is not associated with headache among US children and adolescents. Further prospective studies with larger sample size are needed to validate our findings.
Asunto(s)
Obesidad Infantil , Adulto , Femenino , Humanos , Niño , Adolescente , Obesidad Infantil/complicaciones , Obesidad Infantil/epidemiología , Encuestas Nutricionales , Estudios Transversales , Estudios Prospectivos , Cefalea/epidemiología , Cefalea/etiologíaRESUMEN
Background: The association between dietary energy patterns, calories, and the outcomes of heart failure (HF) is still unclear. Objectives: To evaluate the proper energy intake patterns and daily calorie intake in patients with heart failure among US adults. Methods: The data were derived from the 2001-2014 National Health and Nutrition Examination Survey (NHANES). A calorie intake pattern variable was created using latent class analysis (LCA) based on the calorie ratio of three major nutrients. Cox proportional hazard regression models were used to evaluate the hazard ratios (HR) and 95% confidence intervals (CI) of the association between calorie intake and energy patterns. The primary endpoint was all-cause mortality. Results: Among 991 participants (mean age 67.3 ± 12.9 years; 55.7% men) who suffered from heart failure; the median calorie intake was 1,617 kcal/day [interquartile range (IQR): 1,222-2,154 kcal/day]. In the multivariable-adjusted model, moderate malnutrition was more frequent to death (HR: 2.15; 95% CI: 1.29-3.56). Low-carbohydrate pattern (LCP) and median-carbohydrate pattern (MCP) had lower risks of death compared to high-carbohydrate pattern (HCP) (LCP: HR: 0.76; 95% CI: 0.59-0.97; MCP: HR: 0.77; 95% CI: 0.60-0.98). No association between different amounts of calorie intake and all-cause mortality was found. There was an adjusted significant interaction between calorie intake and energy intake patterns (p = 0.019). There was a linear relationship between energy intake through HCP and all-cause mortality (p for non-linear = 0.557). A non-linear relationship between energy intake through MCP and all-cause mortality (p for non-linear = 0.008) was observed. Conclusion: Both LCP and MCP, compared to HCP, were associated with better outcomes in the HF population. The relationship between energy intake and all-cause death may be influenced by energy intake patterns in HF patients.
RESUMEN
The aim of our study was to determine the prevalence, distribution, and risk factors for constipation in peritoneal dialysis (PD) and hemodialysis (HD) patients in our center. In this cross-sectional study, 858 dialysis patients over 18 years of age (681 HD cases and 177 PD cases from our hospital) were enrolled. A constipation assessment scale (CAS) questionnaire was used to evaluate constipation status. Logistic regression analysis was performed to define independent risk factors for CAS scores. The prevalence of constipation in HD and PD patients was 52.7% and 77.4%, respectively. The mean CAS score in HD and PD patients was 1.73 ± 2.31 and 2.42 ± 2.34, respectively. Age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors associated with constipation in the HD population (OR = 1.67, 95% CI: 1.15-2.90, P = .019; OR = 3.31, 95% CI: 1.65-6.11, P < .001, respectively). In the PD population, only serum prealbumin was independently associated with constipation (OR = 0.88, 95% CI: 0.79-0.96, P = .007). The multivariable logistic regression analysis demonstrated that PD modality, age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors for constipation (OR = 2.15, 95% CI: 1.41-3.32, P < .001; OR = 1.65, 95% CI: 1.13-2.33, P = .003; OR = 3.19, 95% CI: 1.76-5.093, P < .001, respectively). The prevalence of constipation in PD patients was higher than that in HD patients in our center. PD modality for renal replacement therapy, age ≥ 65 and diabetic kidney disease for renal failure were closely associated with constipation in dialysis patients.
Asunto(s)
Nefropatías Diabéticas , Fallo Renal Crónico , Humanos , Adolescente , Adulto , Diálisis Renal/efectos adversos , Estudios Transversales , Prevalencia , Nefropatías Diabéticas/complicaciones , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Estreñimiento/etiología , Estreñimiento/complicacionesRESUMEN
miR-155 was synthesized and loaded into exosomes in increased infiltration of macrophages in a uremic heart. The released exosomal fusion with the plasma membrane leads to the release of miR-155 into the cytosol and translational repression of forkhead transcription factors of the O class (FoxO3a) in cardiomyocytes. Finally, macrophage-derived miR-155-containing exosomes promoted cardiomyocyte pyroptosis and uremic cardiomyopathy changes (cardiac hypertrophy and fibrosis) by directly targeting FoxO3a in uremic mice.