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SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFAs), fatty acids of the phospholipids (FAPLs), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6), and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HSs). COVID-19 patients showed a decrease in Vit E, TPLs, FAPLs, and TFAs in serum in comparison to HSs (p ≤ 0.01), and Vit E treatment restored their levels (p ≤ 0.04). Likewise, there was an increase in IL-6 and CRP in COVID-19 patients in comparison with HSs (p ≤ 0.001), and treatment with Vit E decreased their levels (p ≤ 0.001). Treatment with Vit E as monotherapy can contribute to restoring the modified FA profile of the PLs in the SARS-CoV-2 infection, and this leads to a decrease in lipid peroxidation, OS, and the inflammatory process.
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BACKGROUND: Congenital heart disease (CHD) are the most common malformations from birth. The severity of the different forms of CHD varies extensively from superficial mild lesions with follow-up for decades without any treatment to complex cyanotic malformations requiring urgent surgical intervention. microRNAs have been found to be crucial in cardiac development, giving rise to possible phenotypes in CHD. OBJECTIVES: We aimed to evaluate the expression of miRNAs in 86 children with CHD and divided into cyanotic and non-cyanotic heart defects and 110 controls. METHODS: The miRNAs expression of miR-21-5p, miR-155-5p, miR-221-3p, miR-26a-5p, and miR-144-3p were analyzed by RT-qPCR. In addition, the expressions of the miRNAs studied were correlated with the clinical characteristics of both the children and the mothers. RESULTS: The expression levels of miR-21-5-5p, miR-15-5p5, miR-221-3p, and miR-26-5p significantly differed between CHD and control subjects. Moreover, miR-21-5p levels were higher in patients with cyanotic versus non-cyanotic CHD patients. CONCLUSION: The expression levels of miRNAs of pediatric patients with CHD could participating in the development of cardiac malformations. Additionally, the high expression of miR-21-5p in cyanotic CHD children may be related to greater severity of illness relative to non-cyanotic CHD. IMPACT: This study adds to knowledge of the association between microRNAs and congenital heart disease in children. The expression levels of miR-21-5-5p, miR-15-5p5, miR-221-3p, and miR-26-5p of pediatric patients with CHD could be involved in the development and phenotype present in pediatric patients. miR-21-5p may help to discriminate between cyanotic and non-cyanotic CHD. In the future, the miRNAs studied could have applications as clinical biomarkers.
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Cardiopatías Congénitas , MicroARNs , Humanos , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/sangre , MicroARNs/sangre , MicroARNs/genética , Femenino , Masculino , Preescolar , Lactante , Estudios de Casos y Controles , Niño , Cianosis/sangre , Cianosis/genética , Perfilación de la Expresión GénicaRESUMEN
MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression post-transcriptionally and are crucial in lipid metabolism. ATP-binding cassette transporter A1 (ABCA1) is essential for cholesterol efflux from cells to high-density lipoprotein (HDL). Dysregulation of miRs targeting ABCA1 can affect cholesterol homeostasis and contribute to coronary artery disease (CAD). This study aimed to investigate the expression of miRs targeting ABCA1 in human monocytes, their role in cholesterol efflux, and their relationship with CAD. We included 50 control and 50 CAD patients. RT-qPCR examined the expression of miR-33a-5p, miR-26a-5p, and miR-144-3p in monocytes. Logistic regression analysis explored the association between these miRs and CAD. HDL's cholesterol acceptance was analyzed using the J774A.1 cell line. Results showed that miR-26a-5p (p = 0.027) and ABCA1 (p = 0.003) expression levels were higher in CAD patients, while miR-33a-5p (p < 0.001) levels were lower. Downregulation of miR-33a-5p and upregulation of ABCA1 were linked to a lower CAD risk. Atorvastatin upregulated ABCA1 mRNA, and metformin downregulated miR-26a-5p in CAD patients. Decreased cholesterol efflux correlated with higher CAD risk and inversely with miRs in controls. Reduced miR-33a-5p expression and increased ABCA1 expression are associated with decreased CAD risk. miR deregulation in monocytes may influence atherosclerotic plaque formation by regulating cholesterol efflux. Atorvastatin and metformin could offer protective effects by modulating miR-33a-5p, miR-26a-5p, and ABCA1, suggesting potential therapeutic strategies for CAD prognosis and treatment.
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Transportador 1 de Casete de Unión a ATP , Enfermedad de la Arteria Coronaria , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Masculino , Femenino , Persona de Mediana Edad , Leucocitos Mononucleares/metabolismo , Regulación de la Expresión Génica , Anciano , Línea Celular , Colesterol/metabolismo , Colesterol/sangre , Monocitos/metabolismoRESUMEN
Type 2 diabetes mellitus (T2DM) is associated with various complications, including diabetic foot, which can lead to significant morbidity and mortality. Non-healing foot ulcers in diabetic patients are a major risk factor for infections and amputations. Despite conventional treatments, which have limited efficacy, there is a need for more effective therapies. MicroRNAs (miRs) are small non-coding RNAs that play a role in gene expression and have been implicated in diabetic wound healing. miR expression was analyzed through RT-qPCR in 41 diabetic foot Mexican patients and 50 controls. Diabetic foot patients showed significant increases in plasma levels of miR-17-5p (p = 0.001), miR-191-5p (p = 0.001), let-7e-5p (p = 0.001), and miR-33a-5p (p = 0.005) when compared to controls. Elevated levels of miR-17, miR-191, and miR-121 correlated with higher glucose levels in patients with diabetic foot ulcers (r = 0.30, p = 0.004; r = 0.25, p = 0.01; and r = 0.21, p = 0.05, respectively). Levels of miR-17 showed the highest diagnostic potential (AUC 0.903, p = 0.0001). These findings underscore the possible role of these miRs in developing diabetes complications. Our study suggests that high miR-17, miR-191, and miR-121 expression is strongly associated with higher glucose levels and the development of diabetic foot ulcers.
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MicroARN Circulante , Diabetes Mellitus Tipo 2 , Pie Diabético , Humanos , Pie Diabético/sangre , Pie Diabético/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Masculino , Femenino , Persona de Mediana Edad , MicroARN Circulante/sangre , MicroARN Circulante/genética , Anciano , MicroARNs/sangre , MicroARNs/genética , Biomarcadores/sangre , Estudios de Casos y Controles , Perfilación de la Expresión GénicaRESUMEN
Type II pneumocytes are the target of the SARS-CoV-2 virus, which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. In this study, we evaluated whether treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), lipid peroxidation (LPO), and thiol groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There were significant increases in LPO and carbonyl quantities (p ≤ 0.03) and decreases in TAC and the quantities of NO2-, thiols, and GSH (p < 0.001) in COVID-19 patients. The activities of the antioxidant enzymes such as ecSOD, TrxR, GPx, GST, GR, and peroxidases were decreased (p ≤ 0.04) after the MT treatment. The treatment with MT favored the activity of the antioxidant enzymes that contributed to an increase in TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis, functioning as a glycolytic agent, and inhibited the Warburg effect. Thus, MT restores the redox homeostasis that is altered in COVID-19 patients and can be used as adjuvant therapy in SARS-CoV-2 infection.
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Antioxidantes , Tratamiento Farmacológico de COVID-19 , COVID-19 , Homeostasis , Melatonina , Oxidación-Reducción , Estrés Oxidativo , SARS-CoV-2 , Melatonina/uso terapéutico , Melatonina/farmacología , Humanos , Oxidación-Reducción/efectos de los fármacos , COVID-19/metabolismo , COVID-19/virología , COVID-19/sangre , Homeostasis/efectos de los fármacos , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Anciano , Adulto , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo , Glutatión/sangreRESUMEN
Frailty is a global health problem that impacts clinical practice. It is complex, having a physical and a cognitive component, and it is the result of many contributing factors. Frail patients have oxidative stress and elevated proinflammatory cytokines. Frailty impairs many systems and results in a reduced physiological reserve and increased vulnerability to stress. It is related to aging and to cardiovascular diseases (CVD). There are few studies on the genetic factors of frailty, but epigenetic clocks determine age and frailty. In contrast, there is genetic overlap of frailty with cardiovascular disease and its risk factors. Frailty is not yet considered a risk factor for CVD. It is accompanied by a loss and/or poor functioning of muscle mass, which depends on fiber protein content, resulting from the balance between protein breakdown and synthesis. Bone fragility is also implied, and there is a crosstalk between adipocytes, myocytes, and bone. The identification and assessment of frailty is difficult, without there being a standard instrument to identify or treat it. Measures to prevent its progression include exercises, as well as supplementing the diet with vitamin D and K, calcium, and testosterone. In conclusion, more research is needed to better understand frailty and to avoid complications in CVD.
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Enfermedades Cardiovasculares , Fragilidad , Humanos , Anciano , Fragilidad/complicaciones , Enfermedades Cardiovasculares/complicaciones , Anciano Frágil , Músculo Esquelético , Tejido AdiposoRESUMEN
Marfan syndrome (MFS) is an autosomal dominant disorder caused by a heterozygous mutation of the FBN1 gene. MFS patients present oxidative stress that disturbs redox homeostasis. Redox homeostasis depends in part on the enzymatic antioxidant system, which includes thioredoxin reductase (TrxR) and glutathione peroxidases (GPx), both of which require an adequate concentration of selenium (Se). Therefore, the aim of this study was to determine if Se levels are decreased in the TAA of patients with MFS since this could contribute to the formation of an aneurysm in these patients. The results show that interleukins IL-1ß, IL-6 TGF-ß1, and TNF-α (p ≤ 0.03), and carbonylation (p ≤ 0.03) were increased in the TAA of patients with MFS in comparison with control subjects, while Se, thiols (p = 0.02), TrxR, and GPx (p ≤ 0.001) were decreased. TLR4 and NOX1 (p ≤ 0.03), MMP9 and MMP2 (p = 0.04) and NOS2 (p < 0.001) were also increased. Therefore, Se concentrations are decreased in the TAA of MFS, which can contribute to a decrease in the activities of TrxR and GPx, and thiol groups. A decrease in the activities of these enzymes can lead to the loss of redox homeostasis, which can, in turn, lead to an increase in the pro-inflammatory interleukins associated with the overexpression of MMP9 and MMP2.
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Aneurisma , Síndrome de Marfan , Selenio , Humanos , Aorta Torácica , Reductasa de Tiorredoxina-Disulfuro , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Aneurisma/complicaciones , Glutatión PeroxidasaRESUMEN
MicroRNAs (miRs) regulate gene expression at the post-transcriptional level and are found to be present in monocytes. This study aimed to investigate miR-221-5p, miR-21-5p, and miR-155-5p, their expression in monocytes, and their role in coronary arterial disease (CAD). The study population comprised 110 subjects, and RT-qPCR was used to examine the miR-221-5p, miR-21-5p, and miR-155-5p expressions in monocytes. Results: the miR-21-5p (p = 0.001) and miR-221-5p (p < 0.001) expression levels were significantly higher in the CAD group, and the miR-155-5p (p = 0.021) expression levels were significantly lower in the CAD group; only miR-21-5p and miR-221-5p upregulation was found to be associated with an increased CAD risk. The results show significant increases in miR-21-5p in the unmedicated CAD group with the metformin patients vs. the healthy control group (p = 0.001) and vs. the medicated CAD group with metformin (p = 0.022). The same was true for miR-221-5p in the CAD patients unmedicated with metformin vs. the healthy control group (p < 0.001). Our results from Mexican CAD patients show that the overexpression in monocytes of miR-21-5p and miR-221-5p increases the risk of the development of CAD. In addition, in the CAD group, the metformin downregulated the expression of miR-21-5p and miR-221-5p. Also, the expression of endothelial nitric oxide synthase (NOS3) decreased significantly in our patients with CAD, regardless of whether they were medicated. Therefore, our findings allow for the proposal of new therapeutic strategies for the diagnosis and prognosis of CAD and the evaluation of treatment efficacy.
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Enfermedad de la Arteria Coronaria , MicroARNs , Humanos , Enfermedad de la Arteria Coronaria/metabolismo , Monocitos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
The renal system is engaged in metabolic syndrome (MS) and metabolites of arachidonic acid (AA) participate in renal homeostasis and disruption of functionality. Hibiscus sabdariffa L (HSL) is used as a diuretic and could improve renal function. The aim of this study was to assess if treatment with HSL at 2% improves renal function in MS through the metabolites of AA. A total of 24 male Wistar rats were divided into four groups: Group 1, control (C); Group 2, MS with 30% sucrose in drinking water, Group 3, MS plus HSL infusion at 2% (MS+HSL); and Group 4, C+HSL. We evaluated the perfusion pressure changes (∆-PP), the activities of cyclooxygenases (COXs), the percentage of AA, the expressions of PLA2, COX2, COX1, 5-LOX, TAXS and CYP450, and the concentrations of prostaglandins in the kidney from rats with MS. There was a decrease in the ∆-PP, in the activities of COXs, and the expressions of COX2 and CYP450 (p ≤ 0.03, respectively)as well asPGE2, TxB2, and LKB4 (p ≤ 0.01, respectively). However, the percentage of AA and expressions of PLA2 and PGE1 (p = 0.01, respectively) were increased in C and MS+HSL. The HSL treatment improved the function and anatomical structure of the kidneys in the MS rats, through antioxidant molecules, and inhibited the pathways that metabolize the AA including that of PLA2, COX2, 5-LOX, TAXS, and CYP450 while favoring the COX1 pathway. This improves the vascular resistance of renal arterioles.
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Hibiscus , Síndrome Metabólico , Masculino , Ratas , Animales , Ácido Araquidónico , Ratas Wistar , Ciclooxigenasa 2 , Síndrome Metabólico/tratamiento farmacológico , Riñón/fisiología , Fosfolipasas A2RESUMEN
Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1ß, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFß), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.
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Melatonina , Choque Séptico , Humanos , Antioxidantes/uso terapéutico , Interleucina-6 , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Interleucina-10 , Choque Séptico/tratamiento farmacológico , Reproducibilidad de los Resultados , Estrés Oxidativo , Ácido Ascórbico/uso terapéutico , Vitamina E/uso terapéutico , Acetilcisteína/uso terapéutico , Melatonina/uso terapéutico , Adyuvantes Inmunológicos/uso terapéuticoRESUMEN
BACKGROUND: The left ventricle (LV) journey in their transition from hypertrophy to heart failure is marked by many subcellular events partially understood yet. The moment in which the structural abnormalities reach the umbral to induce myocardial dysfunction remains elusive. AIMS: To evaluate the anatomic-functional relationship between LV wall thickness and longitudinal systolic dysfunction. MATERIAL AND METHODS: We prospectively performed clinical assessment and transthoracic echocardiogram on healthy individuals and hypertensive patients with left ventricle ejection fraction (LVEF) ≥50% and absence of heart failure symptoms. RESULTS: A total of 226 patients and 101 healthy individuals were recruited. The distribution for sex was similar between groups. The mean age was 67±13 years old in the patients, and 44% had concentric LV hypertrophy. LVEF was identical in both groups (63±6%); in contrast, global longitudinal strain (GLS) (-18.8±2.5% vs -20.4±2%) and mitral annulus plane systolic excursion (MAPSE) (13.8±2.8 vs 15.5±2 mm) were lower. ROC curve optimally classified decreased GLS with LV septum thickness ≥13 mm and decreased MAPSE with thickness ≥14 mm. Multivariable logistic regression found that LV septum thickness is the only variable associated with longitudinal systolic dysfunction (OR = 1.1, CI95% = 1.05 - 1.15, P = 0.001, R squared = .38). DISCUSSION: A progressive increase in LV wall thickness due to myocyte hypertrophy and interstitial expansion is associated with LV systolic longitudinal dysfunction. CONCLUSIONS: Patients with moderate or severe ventricular hypertrophy (septum ≥13 mm) had longitudinal systolic dysfunction, GLS decreases with minor structural change than MAPSE, and LVEF is insensitive in detecting longitudinal myocardial dysfunction in patients with hypertension.
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Cardiomiopatías , Hipertensión , Disfunción Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Cardiomiopatías/complicaciones , Cardiomiopatías/diagnóstico por imagen , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico por imagen , Persona de Mediana Edad , Volumen Sistólico , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular IzquierdaRESUMEN
Deodorized garlic (DG) may favor the activity of the antioxidant enzymes and promote the synthesis of hydrogen sulfide (H2S). The objective was to test if DG favors an increase in H2S and if it decreases the oxidative stress caused by lipopolysaccharide (LPS) in rat hearts. A total of 24 rats were divided into 4 groups: Group 1 control (C), Group 2 LPS, Group 3 DG, and Group 4 LPS plus DG. The cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and oxidative stress markers, such as total antioxidant capacity (TAC), glutathione (GSH), selenium (Se), lipid peroxidation (LPO), thiols, hydrogen sulfide (H2S), and the activities and expressions of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), cystathionine synthetase (CBS), cystathionine γ-lyase (CTH), iNOS, and eNOS-p, were analyzed in the heart. Infarct zones in the cardiac tissue were present (p = 0.01). The CMP and CVR decreased and increased (p ≤ 0.05), TAC, GSH, H2S, NO, thiols, and GST activity (p ≤ 0.01) decreased, and LPO and iNOS increased (p ≤ 0.05). The activities and expressions of TrxR, GPx, eNOS-p, CTH, and CBS (p ≤ 0.05) decreased with the LPS treatment; however, DG normalized this effect. DG treatment decreases heart damage caused by LPS through the cross-talk between the H2S and NO systems.
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Ajo , Sulfuro de Hidrógeno , Selenio , Animales , Ratas , Antioxidantes/farmacología , Antioxidantes/metabolismo , Cistationina betasintasa/metabolismo , Cistationina gamma-Liasa/metabolismo , Ajo/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Lipopolisacáridos/farmacología , Estrés Oxidativo , Selenio/farmacología , Compuestos de Sulfhidrilo/farmacología , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Transferasas/metabolismoRESUMEN
In patients with severe pneumonia due to COVID-19, the deregulation of oxidative stress is present. Nuclear erythroid factor 2 (NRF2) is regulated by KEAP1, and NRF2 regulates the expression of genes such as NFE2L2-KEAP1, which are involved in cellular defense against oxidative stress. In this study, we analyzed the participation of the polymorphisms of NFE2L2 and KEAP1 genes in the mechanisms of damage in lung disease patients with SARS-CoV-2 infection. Patients with COVID-19 and a control group were included. Organ dysfunction was evaluated using SOFA. SARS-CoV-2 infection was confirmed and classified as moderate or severe by ventilatory status and by the Berlin criteria for acute respiratory distress syndrome. SNPs in the gene locus for NFE2L2, rs2364723C>G, and KEAP1, rs9676881A>G, and rs34197572C>T were determined by qPCR. We analyzed 110 individuals with SARS-CoV-2 infection: 51 with severe evolution and 59 with moderate evolution. We also analyzed 111 controls. Significant differences were found for rs2364723 allele G in severe cases vs. controls (p = 0.02); for the rs9676881 allele G in moderate cases vs. controls (p = 0.04); for the rs34197572 allele T in severe cases vs. controls (p = 0.001); and in severe vs. moderate cases (p = 0.004). Our results showed that NFE2L2 rs2364723C>G allele G had a protective effect against severe COVID-19, while KEAP1 rs9676881A>G allele G and rs34197572C>T minor allele T were associated with more aggressive stages of COVID-19.
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COVID-19 , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Humanos , COVID-19/genética , Predisposición Genética a la Enfermedad , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , SARS-CoV-2RESUMEN
BACKGROUND: Takayasu arteritis (TAK) is considered a rare disease characterized by nonspecific inflammation of the large arteries, especially the aorta and its major branches. Because TAK is an autoimmune disease (AD), it could share susceptibility loci with other pathologies such as systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), among others. Widely explored polymorphisms in non-HLA genes, including TNFAIP3, STAT4, TNFSF4, BANK1, and BLK have been consistently associated with both SLE and RA, but they have not been evaluated in TAK. OBJECTIVE: The aim of our study was to investigate whether TNFAIP3, STAT4, BANK1, BLK, and TNFSF4 polymorphisms are associated with susceptibility to TAK. METHODS: The TNFAIP3 rs2230926T/G and rs5029924C/T, STAT4 rs7574865G/T, BANK1 10516487G/A, BLK rs2736340T/C, rs13277113A/G, and TNFS4 rs2205960G/T polymorphisms were genotyped in 101 cases and 276 controls by using a TaqMan SNP genotyping assay. An association analysis was performed. RESULTS: The TNFAIP3 rs2230926T/G and rs5029924C/T polymorphisms were in complete linkage disequilibrium and turned out to be risk factors for TAK (OR = 4.88, p = 0.0001). The STAT4, BANK1, BLK, and TNFSF4 polymorphisms were not associated with the disease. CONCLUSIONS: This is the first study documenting an association of TNFAIP3 rs2230926T/G and rs5029924C/T with TAK. Our results provide new information on the genetic bases of TAK.
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Genotipo , Arteritis de Takayasu/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Proteínas de la Membrana/genética , Persona de Mediana Edad , Ligando OX40/genética , Polimorfismo de Nucleótido Simple , Factor de Transcripción STAT4/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Familia-src Quinasas/genéticaRESUMEN
OBJECTIVES: There is no consensus on how to evaluate inflammatory activity in Takayasu's arteritis (TAK). Here we compare biochemical tests and three clinical scores, which evaluate inflammatory activity (IA) in TAK, versus quantitative 18F-FDG PET/CT as the gold standard. METHODS: This prospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria. IA was assessed through laboratory tests, clinical scores of the National Institute of Health (NIH), Dabague-Reyes (DR) and the Indian Takayasu Clinical Activity Score 2010 (ITAS2010), and the result of these assessments was compared against 18F-FDG PET/CT Standardised Uptake Values (SUVmax). RESULTS: A total of 35 patients were studied, 86% were women. SUVmax had positive correlations with acute phase reactants and DR and NIH. Agreement of 18F-FDG PET/CT was significant with erythrocyte sedimentation rate (ESR) and DR score. Receiver Operating Characteristic (ROC) curve analysis showed diagnostic value for inflammatory activity in ESR, DR and NIH scores, which had higher specificity when they were estimated with new cut-off points for the Mexican population. CONCLUSIONS: ESR and other phase reactants have good sensitivity but low specificity to evaluate IA in TAK when compared against 18F-FDG PET/CT. Among all the clinical scores, DR had the best diagnostic value, with strong potential as a clinical tool to define the inflammatory status in TAK patients when the study image is not available. However, in complex TAK cases with doubtful diagnosis after assessment by clinical scores or laboratory, 18F-FDG PET/CT remains mandatory.
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Fluorodesoxiglucosa F18 , Arteritis de Takayasu , Biomarcadores , Femenino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Estudios Prospectivos , Radiofármacos , Arteritis de Takayasu/diagnóstico por imagenRESUMEN
Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and size of adipocytes, promoting lipogenesis, stimulating differentiation of preadipocytes to mature adipocytes, and regulating the energy balance in hypothalamic neurons that control appetite. This review discusses the participation of oxidative stress in obesity and the important groups of compounds found in plants with antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, and isoflavones), and curcuminoids (b) carotenoids, (c) capsaicinoids and casinoids, (d) isothiocyanates, (e) catechins, and (f) vitamins. Examples are analyzed, such as resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, and garlic. The antioxidant activities of these compounds depend on their activities as reactive oxygen species (ROS) scavengers and on their capacity to prevent the activation of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells), and reduce the expression of target genes, including those participating in inflammation. We conclude that natural compounds have therapeutic potential for diseases mediated by oxidative stress, particularly obesity. Controlled and well-designed clinical trials are still necessary to better know the effects of these compounds.
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Depuradores de Radicales Libres , Obesidad , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/uso terapéutico , Humanos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/patología , Extractos Vegetales/química , Extractos Vegetales/uso terapéuticoRESUMEN
Metabolic syndrome (MS) is the association of three or more pathologies among which obesity, hypertension, insulin resistance, dyslipidemia, and diabetes are included. It causes oxidative stress (OS) and renal dysfunction. Hibiscus sabdariffa L. (HSL) is a source of natural antioxidants that may control the renal damage caused by the MS. The objective of this work was to evaluate the effect of a 2% HSL infusion on renal function in a MS rat model induced by the administration of 30% sucrose in drinking water. 24 male Wistar rats were divided into 3 groups: Control rats, MS rats and MS + HSL rats. MS rats had increased body weight, systolic blood pressure, triglycerides, insulin, HOMA index, and leptin (p ≤ 0.04). Renal function was impaired by an increase in perfusion pressure in the isolated and perfused kidney, albuminuria (p ≤ 0.03), and by a decrease in clearance of creatinine (p ≤ 0.04). The activity of some antioxidant enzymes including the superoxide dismutase isoforms, peroxidases, glutathione peroxidase, glutathione-S-transferase was decreased (p ≤ 0.05). Lipoperoxidation and carbonylation were increased (p ≤ 0.001). The nitrates/nitrites ratio, total antioxidant capacity, glutathione levels and vitamin C were decreased (p ≤ 0.03). The treatment with 2% HSL reversed these alterations. The results suggest that the treatment with 2% HSL infusion protects renal function through its natural antioxidants which favor an improved renal vascular response. The infusion contributes to the increase in the glomerular filtration rate, by promoting an increase in the enzymatic and non-enzymatic antioxidant systems leading to a decrease in OS and reestablishing the normal renal function.
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Albuminuria/tratamiento farmacológico , Fármacos Antiobesidad/farmacología , Antioxidantes/farmacología , Hibiscus/química , Hipolipemiantes/farmacología , Riñón/efectos de los fármacos , Síndrome Metabólico/tratamiento farmacológico , Albuminuria/sangre , Albuminuria/patología , Animales , Fármacos Antiobesidad/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Ácido Ascórbico/sangre , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Tasa de Filtración Glomerular/efectos de los fármacos , Glutatión/sangre , Glutatión Peroxidasa/sangre , Glutatión Transferasa/sangre , Hipolipemiantes/aislamiento & purificación , Insulina/sangre , Riñón/metabolismo , Riñón/fisiopatología , Leptina/sangre , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/patología , Extractos Vegetales/química , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre , Triglicéridos/sangreRESUMEN
INTRODUCTION: Aortic calcification is a frequent finding in Takayasu arteritis (TA). The aim of this study was to evaluate the risk factors for aortic calcification in TA and its relationship with disease activity and the presence and type of vascular lesion. METHODS: Nineteen patients with TA underwent nonenhanced computed tomography to measure the calcium score of the aorta and its main branches, which were divided into 13 segments. In each segment, the type of vascular lesion was evaluated by noninvasive angiography. Clinical risk factors and disease activity scores were recorded. RESULTS: Eighteen of 19 patients (95%) were women, with a median age of 25 years. Median of calcium score was 69 AU (0-12,465 AU). Eleven of 19 patients (57.9%) had calcium score greater than 0. Age, evolution time, and dyslipidemia were higher in patients with calcium, whereas the National Institutes Health and Dabague disease activity scores were lower. There was no association between the presence of calcium and vascular lesion: 60 of 160 segments (37.5%) without calcium had some lesion, compared with 24 of 68 (35.3%) with calcium score greater than 0, p = 0.75. However, occlusion was more frequent in patients with calcium, whereas wall thickening was in those without calcium. CONCLUSIONS: Aortic calcification in TA is related to age, evolution time, and abnormalities in lipid profile and occlusion and, inversely with some activity scores. Identification of calcification could be useful in identifying patients that even without significant lesions might have accelerated atherosclerosis, and who might be benefited with specific treatment.
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Arteritis de Takayasu , Calcificación Vascular , Adulto , Factores de Edad , Angiografía , Aorta , Femenino , Humanos , Masculino , Factores de Riesgo , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/diagnóstico , Arteritis de Takayasu/epidemiología , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiologíaRESUMEN
Cardiovascular diseases are being included in the study of developmental origins of health and disease (DOHaD) and essential systemic hypertension has also been added to this field. Epigenetic modifications are one of the main mechanisms leading to early programming of disease. Different environmental factors occurring during critical windows in the early stages of life may leave epigenetic cues, which may be involved in the programming of hypertension when individuals reach adulthood. Such environmental factors include pre-term birth, low weight at birth, altered programming of different organs such as the blood vessels and the kidney, and living in disadvantageous conditions in the programming of hypertension. Mechanisms behind these factors that impact on the programming include undernutrition, oxidative stress, inflammation, emotional stress, and changes in the microbiota. These factors and their underlying causes acting at the vascular level will be discussed in this paper. We also explore the establishment of epigenetic cues that may lead to hypertension at the vascular level such as DNA methylation, histone modifications (methylation and acetylation), and the role of microRNAs in the endothelial cells and blood vessel smooth muscle which participate in hypertension. Since epigenetic changes are reversible, the knowledge of this type of markers could be useful in the field of prevention, diagnosis or epigenetic drugs as a therapeutic approach to hypertension.
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Hipertensión Esencial/etiología , Adulto , Animales , Metilación de ADN , Epigénesis Genética , Hipertensión Esencial/genética , Hipertensión Esencial/metabolismo , Hipertensión Esencial/patología , Código de Histonas , Humanos , Microbiota , Estrés OxidativoRESUMEN
: Reactive nitrogen species (RNS) are formed when there is an abnormal increase in the level of nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) and/or by the uncoupled endothelial nitric oxide synthase (eNOS). The presence of high concentrations of superoxide anions (O2-) is also necessary for their formation. RNS react three times faster than O2- with other molecules and have a longer mean half life. They cause irreversible damage to cell membranes, proteins, mitochondria, the endoplasmic reticulum, nucleic acids and enzymes, altering their activity and leading to necrosis and to cell death. Although nitrogen species are important in the redox imbalance, this review focuses on the alterations caused by the RNS in the cellular redox system that are associated with cardiometabolic diseases. Currently, nitrosative stress (NSS) is implied in the pathogenesis of many diseases. The mechanisms that produce damage remain poorly understood. In this paper, we summarize the current knowledge on the participation of NSS in the pathology of cardiometabolic diseases and their possible mechanisms of action. This information might be useful for the future proposal of anti-NSS therapies for cardiometabolic diseases.