RESUMEN
BACKGROUND: Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. METHODS: Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants' glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. RESULTS: Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. CONCLUSIONS: A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. TRIAL REGISTRATION: The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070.
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Biomarcadores , Glucemia , Diabetes Mellitus Tipo 2 , Ayuno , Obesidad , Fosfatidilcolina-Esterol O-Aciltransferasa , Humanos , Masculino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Ayuno/sangre , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Resultado del Tratamiento , Obesidad/sangre , Obesidad/diagnóstico , Obesidad/dietoterapia , Obesidad/fisiopatología , Obesidad/terapia , Glucemia/metabolismo , Factores de Tiempo , Biomarcadores/sangre , Restricción Calórica , Arildialquilfosfatasa/sangre , HDL-Colesterol/sangre , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Pérdida de Peso , Anciano , Adulto , Dieta Saludable , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Ayuno IntermitenteRESUMEN
Current data suggest that oxidative stress may play an important role in the occurrence of acute central serous chorioretinopathy (CSC), as chorioretinal integrity may be affected by disruption of the patient's metabolic redox balance, indicating the need for biomarkers. In addition to oxidative stress, high-density lipoprotein (HDL) dysfunction due to dyslipidemia can also lead to many types of physical discomfort. However, little is known about the pathophysiology of the disease resulting from oxidative stress and HDL dysfunction in CSC. The aim of this study was to investigate whether serum oxidative stress and HDL functionality markers have an impact on CSC disease. The case series of this study included 33 consecutive patients with treatment-naïve acute CSC. Thirty-five healthy volunteers of similar age were included in this study as non-CSC controls. Serum samples of the participants were taken and routine lipid values, serum Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidized Low Density Lipoprotein (ox-LDL), and Paraoxonase (PON1) levels were measured quantitatively. Serum oxidative stress index (OSI) was then calculated. Serum Ox-LDL, TOS and OSI levels in the acute CSC group, consisting of patients who had never been treated before and had no other disease, were statistically significantly higher than the control group. Conversely, serum PON1 and TAS levels were lower in CSC than in the control group. The relationship between CSC and deterioration in serum redox balance and decrease in PON1 activity, an important marker of HDL functionality, was demonstrated for the first time through this study. According to the literature, serum levels of these biomarkers, which identify acute/chronic inflammation and oxidative stress, have not been measured before in CSC disease. Finally, it is conceivable that redox balance and HDL functionality may be important in the diagnosis and treatment of the acute phase of CSC.
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Arildialquilfosfatasa , Biomarcadores , Coriorretinopatía Serosa Central , Lipoproteínas LDL , Estrés Oxidativo , Humanos , Coriorretinopatía Serosa Central/sangre , Coriorretinopatía Serosa Central/metabolismo , Masculino , Biomarcadores/sangre , Femenino , Adulto , Arildialquilfosfatasa/sangre , Arildialquilfosfatasa/metabolismo , Persona de Mediana Edad , Lipoproteínas LDL/sangre , Lipoproteínas HDL/sangre , Antioxidantes/metabolismo , Estudios de Casos y ControlesRESUMEN
Cardiovascular disease is one of the leading causes of death worldwide. Evidence suggests that alterations in the gut microbiome could play a role in cardiovascular diseases, including heart failure. The purpose of this study was to evaluate the effect of synbiotics on serum paraoxonase 1(PON1), soluble CD163/soluble TNF-like weak inducer of apoptosis (sCD163/sTWEAK), and lipid profile, which are involved in heart failure in patients with chronic heart failure. In this triple-blind randomized clinical trial, 90 eligible patients were included in the study. They were randomly assigned to receive one capsule (500 mg) of synbiotics or a placebo daily for ten weeks. Serum PON1, sCD163/sTWEAK, and lipid profiles were measured at the beginning and end of the study. The data were analyzed by SPSS 24, and the p-value < 0.05 was considered statistically significant. Among 90 patients who met the inclusion criteria, 80 completed the study. The primary outcomes showed a small effect on sTWEAK, with an adjusted standard mean difference (SMD) of 0.2. However, no significant changes were observed in sCD163/sTWEAK (SMD: 0.16). Secondary outcomes indicated no changes in PON1, total cholesterol (TC), or LDL-C levels. However, there was an increase in HDL-C levels (adjusted SMD: 0.46, 95% CI: 0.02-0.91) and a decrease in TG and TC/HDL levels (adjusted SMD: - 0.5 and - 0.3, respectively) in the synbiotic group. A favorable effect of synbiotics on sTWEAK, HDL, TG, and TC/HDL of patients with heart failure was observed, but no statistically significant effect was found on sCD163/sTWEAK, PON1, LDL, and TC factors.
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Arildialquilfosfatasa , Insuficiencia Cardíaca , Simbióticos , Humanos , Arildialquilfosfatasa/sangre , Masculino , Femenino , Simbióticos/administración & dosificación , Insuficiencia Cardíaca/sangre , Persona de Mediana Edad , Anciano , Receptores de Superficie Celular/sangre , Antígenos CD/sangre , Citocina TWEAK/sangre , Lipoproteínas/sangre , Enfermedad Crónica , Biomarcadores/sangre , Antígenos de Diferenciación MielomonocíticaRESUMEN
BACKGROUND: Direct oral anticoagulants (DOACs) have high potency against their therapeutic target and are widely used in the treatment of atrial fibrillation (AF). Most DOACs are often claimed to have adverse effects due to off-target inhibition of essential proteins. Human serum paraoxonase 1 (PON1), one of the essential proteins, known for its anti-inflammatory and antioxidant properties, could be affected by DOACs. Thus, a comparative evaluation of DOACs and their effect on PON1 protein will aid in recommending the most effective DOACs for AF treatment. This study aimed to assess the impact of DOACs on PON1 through a combination of computational and experimental analyses. METHODS: We focus on apixaban, dabigatran, and rivaroxaban, the most recommended DOACs in AF treatment, for their impact on PON1 through molecular docking and molecular dynamics (MD) simulation to elucidate the binding affinity and drug-protein structural stability. This investigation revealed the most influential DOACs on the PON1 protein. Then experimental validation was performed in DOAC-treated AF participants (n = 42; 19 treated with dabigatran and 23 treated with rivaroxaban) compared to a healthy control group (n = 22) through gene expression analysis in peripheral blood mononuclear cells (PBMC) and serum enzyme concentration. RESULTS: Our computational investigation showed rivaroxaban (-4.24 kcal/mol) exhibited a lower affinity against the PON1 protein compared to apixaban (-5.97 kcal/mol) and dabigatran (-9.03 kcal/mol) through molecular docking. Dabigatran holds complex interactions with PON1 at GLU53, TYR197, SER193, and ASP269 by forming hydrogen bonds. Additionally, MD simulation revealed that dabigatran disrupts PON1 stability, which may contribute functional changes. Further experimental validation revealed a significant down-regulation (p < 0.05) of PON1 gene expression in PBMC and decreased serum PON1 enzyme concentration on DOAC treatment. Rivaroxaban as about 48% has inhibitory percentage and dabigatran as about 75% of inhibitory percentage compared to healthy control. CONCLUSION: Overall, our computational and experimental results clearly show the higher inhibitory effect of dabigatran than rivaroxaban. Hence, rivaroxaban will be a better drug candidate for improving the outcome of AF.
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Arildialquilfosfatasa , Fibrilación Atrial , Dabigatrán , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Piridonas , Rivaroxabán , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/metabolismo , Arildialquilfosfatasa/sangre , Rivaroxabán/uso terapéutico , Masculino , Piridonas/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Pirazoles/química , Administración Oral , Anticoagulantes/farmacología , Anticoagulantes/química , Femenino , Anciano , Persona de Mediana EdadRESUMEN
Consistent information and standardization procedures regarding the time of storage for frozen samples and the effects of storage time on enzyme activity are still missing in the literature. Thus, we evaluated the effects of different storage temperatures (-20 °C and - 80 °C), three repetitive freeze/thaw cycles, and 24-h mimic transportation on the activities of PON1 (paraoxonase and arylesterase), enzymes involved in the protection and detoxification processes of reactive molecules. PON1 enzymes' activity was validated on serum and heparinized plasma in horses. The results revealed that conditions and time of storage of blood samples for PON1 analyses altered the activities of both enzymes in both sample types, evidencing that these conditions can lead to protein degradation or general alteration. Specifically, paraoxonase and arylesterase activities significantly decreased among storage temperatures, with major effects detected at -20 °C. The repeated freeze/thaw cycles at -20 °C and 24-h mimic transport conditions also generated an expected degradation of the arylesterase in both serum and heparinized plasma while freeze/thaw cycles at -80 °C caused an increase of both arylesterase and paraoxonase activities on both sample types. In general, similar enzyme responses were detected between serum and heparinized plasma.
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Arildialquilfosfatasa , Hidrolasas de Éster Carboxílico , Congelación , Animales , Caballos/sangre , Arildialquilfosfatasa/sangre , Arildialquilfosfatasa/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/sangre , Heparina/farmacología , Transportes , Plasma/enzimología , Plasma/química , Estabilidad de Enzimas , Masculino , Manejo de Especímenes/veterinariaRESUMEN
Polyunsaturated fatty acids (PUFA) are known to have a regulatory effect on oxidative and inflammatory processes. This study aimed to identify the relationship between blood PUFA status and circulatory markers of oxidative stress and inflammation in a cohort of 172 subjects. The population was divided by sex and into three age groups: adults (18-64 years old, n = 69), older adults (65-89 years old, n = 54), and long-lived individuals (LLIs, 90-111 years old, n = 49). Whole blood PUFA content was quantified using gas chromatography. Additionally, serum levels of C-reactive protein (CRP), paraoxonase (PON), Trolox equivalent antioxidant capacity (TEAC), and malondialdehyde (MDA) were measured. Our results showed that a higher omega-3 (n-3) index in adult females was a predictor of lower MDA concentrations (p = 0.038). Conversely, total n-3 PUFA and total n-6 PUFA were positively related to MDA values among older adult females and LLI men (p < 0.05), while total n-6 PUFA was inversely correlated with MDA levels in LLI females (p < 0.05). Interestingly, increased concentrations of total n-3 PUFA and n-3 index were positively correlated with higher TEAC values in LLI men (p = 0.007), while the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio was inversely correlated with TEAC values among LLI females (p = 0.006). These findings suggest that cellular antioxidant capacity is inversely correlated with changes in the AA/EPA ratio in long-lived females, whereas n-3 PUFA may enhance blood antioxidant capacity in long-lived men. Overall, our study highlights the complex, sex-specific interactions between PUFA profiles and oxidative stress and inflammatory markers across different age groups.
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Biomarcadores , Ácidos Grasos Insaturados , Inflamación , Longevidad , Malondialdehído , Estrés Oxidativo , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Estudios Transversales , Biomarcadores/sangre , Anciano de 80 o más Años , Inflamación/sangre , Longevidad/fisiología , Adulto Joven , Malondialdehído/sangre , Ácidos Grasos Insaturados/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Adolescente , Ácidos Grasos Omega-3/sangre , Arildialquilfosfatasa/sangre , Antioxidantes/metabolismo , Antioxidantes/análisis , Envejecimiento/sangreRESUMEN
Paraoxonase 1 (PON1) is one of the most significant antioxidative enzymes associated with high-density lipoprotein (HDL). It has been proved that is involved in the pathogenesis of many diseases including chronic kidney disease (CKD). The association between PON1 and CKD seems to be mutual, such that the disease produces a significant decrease in PON1 activity levels, while the genetics of PON1 may affect the risk of susceptibility to CKD. Recent studies reveal that the decrease in serum PON1 activity observed in non-dialyzed and dialyzed CKD patients as well as in renal transplant (RT) patients is linked to an increased vulnerability to atherosclerosis. We intend to summarize current literature concerning PON1 activity in CKD, highlighting on the main determinants of PON1 activity, its association with oxidative stress, the impact of its genetic polymorphism on the disease development, the effect of drugs and nutritional state. Furthermore, evidence supporting the implication of reduced PON1 activity in the incident of cardiovascular disease in CKD patients, is also examined. It appears that despite the lack of standardization of PON1 activity measurement, PON1 remains a valuable biomarker for the researchers through the last decades, which contributes to the assessment of the antioxidant status having prognostic benefit on adverse clinical outcomes at various stages and etiologies of kidney disease.
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Arildialquilfosfatasa , Estrés Oxidativo , Insuficiencia Renal Crónica , Arildialquilfosfatasa/metabolismo , Arildialquilfosfatasa/genética , Arildialquilfosfatasa/sangre , Humanos , Insuficiencia Renal Crónica/complicaciones , Biomarcadores/sangre , Polimorfismo Genético , Enfermedades Cardiovasculares/etiología , Trasplante de Riñón , Aterosclerosis/etiología , PronósticoRESUMEN
AIM: To compare the Paraoxonase 1 (PON1) activity and phenotype distribution between lumbar disc herniation (LDH) patients and healthy individuals. MATERIAL AND METHODS: This research included 40 LDH patients and 42 healthy individuals. Spectrophotometric assays were performed to determine the serum PON1 and arylesterase activities. The PON1 ratio, which represents the salt-stimulated PON/ arylesterase level, demonstrated a trimodal distribution. This ratio was applied to identify the different phenotypes; QQ, QR, and RR of each subject. RESULTS: The LDH patients had lower PON1 activity than the healthy individuals (p < 0.05). LDH patients had a statistically significant QQ phenotype compared to the healthy subjects (p < 0.05). CONCLUSION: LDH patients had statistically lower PON1 activity, suggesting that the low PON1 activity and PON1 QQ phenotype may be a risk factor for LDH occurrence.
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Arildialquilfosfatasa , Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Fenotipo , Humanos , Arildialquilfosfatasa/metabolismo , Arildialquilfosfatasa/sangre , Arildialquilfosfatasa/genética , Masculino , Femenino , Adulto , Persona de Mediana Edad , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/sangreRESUMEN
High density lipoprotein (HDL) functions are mostly mediated through a complex proteome, particularly its enzymes. HDL can provide a scaffold for the assembly of several proteins that affect each other's function. HDL particles, particularly small, dense HDL3, are rich in paraoxonase 1 (PON1), which is an important enzyme in the functionality of HDL, so the antioxidant and antiatherogenic properties of HDL are largely attributed to this enzyme. There is an increasing need to represent a valid, reproducible, and reliable method to assay HDL function in routine clinical laboratories. In this context, HDL-associated proteins may be key players; notably PON1 activity (its arylesterase activity) may be a proper candidate because its decreased activity can be considered an important risk factor for HDL dysfunctionality. Of note, automated methods have been developed for the measurement of serum PON1 activity that facilitates its assay in large sample numbers. Arylesterase activity is proposed as a preferred activity among the different activities of PON1 for its assay in epidemiological studies. The binding of PON1 to HDL is critical for the maintenance of its activity and it appears apolipoprotein A-I plays an important role in HDL-PON1 interaction as well as in the biochemical and enzymatic properties of PON1. The interrelationships between HDL, PON1, and HDL's other components are complex and incompletely understood. The purpose of this review is to discuss biochemical and clinical evidence considering the interactions of PON1 with HDL and the role of this enzyme as an appropriate biomarker for HDL function as well as a potential therapeutic target.
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Arildialquilfosfatasa , Lipoproteínas HDL , Arildialquilfosfatasa/metabolismo , Arildialquilfosfatasa/sangre , Humanos , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/sangre , Relevancia ClínicaRESUMEN
Objectives: To examine the influence of hirudotherapy on parameters of oxidative stress. METHODS: The cross-sectional study was conducted from March 29 to September 29, 2021, at the Alanya Research and Training Hospital's Traditional and Complementary Medicine Application Centre, Turkey, and comprised adult volunteers of either gender. The participants were subjected to two sessions of hirudotherapy 4 weeks apart. Total antioxidant status, total oxidant status, oxidative stress index values, ischaemia-modified albumin level, paraoxonase 1, disulfide, native thiol, total thiol, and arylesterase levels were assessed at baseline and after the second hirudotherapy session. Data was analysed using SPSS 15. RESULTS: Of the 50 subjects, 30(60%) were females and 20(40%) were males. The overall mean age was 47.10±15.16 years. Oxidative stress, ischaemia-modified albumin and disulfide levels decreased, but not significantly (p>0.05). The reduction in disulfide levels was significant (p=0.021). CONCLUSIONS: Hirudotherapy, within its limitations, could reduce oxidative stress.
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Antioxidantes , Arildialquilfosfatasa , Hidrolasas de Éster Carboxílico , Estrés Oxidativo , Albúmina Sérica Humana , Humanos , Femenino , Masculino , Adulto , Antioxidantes/metabolismo , Arildialquilfosfatasa/sangre , Arildialquilfosfatasa/metabolismo , Estudios Transversales , Persona de Mediana Edad , Albúmina Sérica Humana/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/sangre , Disulfuros/sangre , Compuestos de Sulfhidrilo/sangre , Oxidantes/sangre , Oxidantes/metabolismo , TurquíaRESUMEN
Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.
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Biomarcadores , Enfermedades Cardiovasculares , Proteínas Relacionadas con la Folistatina , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arildialquilfosfatasa/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/sangre , Estudios de Casos y Controles , Proteínas Relacionadas con la Folistatina/sangre , Hipertensión/epidemiología , Hipertensión/sangre , Hipertensión/diagnóstico , México/epidemiología , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
Introduction: paraoxonase 1 (PON1) is a high-density lipoprotein (HDL) associated enzyme that has anti-inflammatory, anti-atherogenic, and antioxidant functions. PON1 is noted to be a determinant of resistance to the development of atherosclerosis through hydrolysis of phospholipid and cholesteryl ester hydroperoxides. This study was designed to assess PON1 activity levels among patients with type 2 diabetes mellitus (T2DM) in Southwest Nigeria. Methods: this was a cross-sectional study done over a period of six months. A total of 138 participants; 69 with T2DM and 69 apparently healthy controls were recruited for this study. Fasting plasma glucose (FPG), HDL cholesterol (HDL-c), and PON1 activity were analyzed in the participants. The comparison of the mean between the groups of participants was assessed using the independent student t-test while the Mann-Whitney U test was used to compare two medians. The p-value was set at 0.05. Results: mean age for participants with T2DM was 54.90 ± 8.1 years and the healthy control group was 54.12 ± 8.4 years, with a p-value of 0.549. The male-to-female ratio was 0.47 for both participants with T2DM and healthy controls. Participants with T2DM had significantly higher median glucose concentration of 109.18 mg/dl compared with 82.58 mg/dl among controls, p-value <0.001. Median serum HDL-c was lower in diabetics compared to controls (52.66 mg/dl vs 57.92 mg/dl; p-value < 0.001). PON1 activity was lower in T2DM compared with that of the controls (690.11 pmol/min/ml vs 3379.7 pmol/min/ml; p-value <0.001). Paroxonase 1 showed a non-significant positive correlation with HDL-c and a negative correlation with FPG, and body mass index (BMI). Conclusion: these findings suggest that PON1 activity is lower in T2DM compared to healthy controls and a lower PON1 activity level was seen among female diabetics compared with the male diabetics.
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Arildialquilfosfatasa , Aterosclerosis , Diabetes Mellitus Tipo 2 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arildialquilfosfatasa/sangre , HDL-Colesterol , Estudios Transversales , Hospitales de Enseñanza , NigeriaRESUMEN
The development of inexpensive, fast, and reliable screening tests for COVID-19 is, as yet, an unmet need. The present study was aimed at evaluating the usefulness of serum arylesterase activity of paraoxonase-1 (PON1) measurement as a screening test in patients with different severity levels of COVID-19 infection. We included 615 COVID-19-positive patients who were classified as asymptomatic, mildly symptomatic, severely symptomatic, or fatally symptomatic. Results were compared with 50 healthy volunteers, 330 patients with cancer, and 343 with morbid obesity. Results showed PON1 activity greatly decreased in COVID-19 compared to healthy volunteers; a receiver operating characteristics plot showed a high diagnostic accuracy. The degree of COVID-19 severity did not influence PON1 levels. Our results indicated that PON1 determination was efficient for disease diagnosis, but not for prognosis. Furthermore, patients with obesity or cancer presented alterations similar to those of COVID-19 patients. As such, elevated levels of PON1 indicate the absence of COVID-19, but low levels may be present in various other chronic diseases. The assay is fast and inexpensive. We suggest that PON1 measurement could be used as an initial, high cut-off point screening method, while lower values should be confirmed with the more expensive nucleic acid amplification test.
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Arildialquilfosfatasa , COVID-19 , Arildialquilfosfatasa/sangre , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/enzimología , Hidrolasas de Éster Carboxílico , Humanos , SueroRESUMEN
Metabolic syndrome is a multiplex of the risk factor for the development of type 2 diabetes and cardiovascular disease and it reflects the clustering of multiple risk factors resulting from obesity and insulin resistance. Despite its predominance in obese individuals, MS does occur in non-obese individuals. Many individuals characterized as normal weight as per their body mass index (BMI), have increased visceral adiposity thereby leading to an unfavorable inflammatory cytokine profile and altered PON levels. There are limited studies from India concerning inflammatory cytokines in obesity and MS in general and non-obese patients with MS in particular. MATERIAL: Study Design: An observational cross sectional comparative study was conducted which included 65 patients in each Obese and Non-obese Metabolic Syndrome group. The difference in biomarker profile between the two groups was studied. MATERIAL AND METHODS: Patients were subjected to detailed history, physical and anthropometric examination. NCEP-ATP III criteria were used for the diagnosis of Metabolic Syndrome. Patients were considered obese if BMI ≥ 25kg/m2. Normal weight individuals with MS were further subdivided into two groups based on the presence of abdominal obesity (WC cut off 90 cm for men and 80 cm for women). Blood samples were collected for analysis for FBS, Lipid Profile, and HbA1c. Blood samples for biomarker analysis were collected in clotted sample tubes followed by deep freezing and analyzed using ELISA kits. The results were interpreted according to manufacturer guidelines. OBSERVATION: There were no significant differences in IL-6, TNF-α, and PON 1 profiles among Obese and Non-obese Metabolic Syndrome. Moreover significant (p < 0.05) positive correlation was seen in TNF-α levels among patients with abdominal obesity than without abdominal obesity among the Non-obese group. CONCLUSION: TNF-α levels were significantly higher among patients with abdominal obesity than without abdominal obesity among the Non-obese group. There was no significant difference in IL-6, TNF-alpha, and PON 1 among Obese and Non-obese MS. This finding indicates that apart from adipose tissue, other factors are also responsible for the development of MS and its associated proinflammatory profile. There could be a significant contribution of genetic and epigenetic factors which need to be further explored.
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Arildialquilfosfatasa/sangre , Diabetes Mellitus Tipo 2 , Interleucina-6/sangre , Síndrome Metabólico , Biomarcadores , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Masculino , Obesidad/complicaciones , Obesidad Abdominal/complicaciones , Factor de Necrosis Tumoral alfaRESUMEN
The aim of our observational study was to derive a small set out of 92 repeatedly measured biomarkers with optimal predictive capacity for adverse clinical events in heart failure, which could be used for dynamic, individual risk assessment in clinical practice. In 250 chronic HFrEF (CHF) patients, we collected trimonthly blood samples during a median of 2.2 years. We selected 537 samples for repeated measurement of 92 biomarkers with the Cardiovascular Panel III (Olink Proteomics AB). We applied Least Absolute Shrinkage and Selection Operator (LASSO) penalization to select the optimal set of predictors of the primary endpoint (PE). The association between repeatedly measured levels of selected biomarkers and the PE was evaluated by multivariable joint models (mvJM) with stratified fivefold cross validation of the area under the curve (cvAUC). The PE occurred in 66(27%) patients. The optimal set of biomarkers selected by LASSO included 9 proteins: NT-proBNP, ST2, vWF, FABP4, IGFBP-1, PAI-1, PON-3, transferrin receptor protein-1, and chitotriosidase-1, that yielded a cvAUC of 0.88, outperforming the discriminative ability of models consisting of standard biomarkers (NT-proBNP, hs-TnT, eGFR clinically adjusted) - 0.82 and performing equally well as an extended literature-based set of acknowledged biomarkers (NT-proBNP, hs-TnT, hs-CRP, GDF-15, ST2, PAI-1, Galectin 3) - 0.88. Nine out of 92 serially measured circulating proteins provided a multivariable model for adverse clinical events in CHF patients with high discriminative ability. These proteins reflect wall stress, remodelling, endothelial dysfunction, iron deficiency, haemostasis/fibrinolysis and innate immunity activation. A panel containing these proteins could contribute to dynamic, personalized risk assessment.Clinical Trial Registration: 10/05/2013 https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 .
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Biomarcadores/sangre , Insuficiencia Cardíaca/sangre , Inmunidad Innata/genética , Medicina de Precisión , Anciano , Antígenos CD/sangre , Arildialquilfosfatasa/sangre , Enfermedad Crónica/epidemiología , Enfermedad Crónica/prevención & control , Proteínas de Unión a Ácidos Grasos/sangre , Femenino , Galectina 3/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/patología , Hexosaminidasas/sangre , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Receptores de Transferrina/sangre , Medición de Riesgo , Factores de RiesgoRESUMEN
INTRODUCTION: Adiponectin is a potent vascular protective molecule. Recent findings have suggested adiponectin resistance during early diabetes. However, the molecular mechanisms responsible remain unidentified. Here, we took an unbiased approach to identify whether hyperlipidemic plasma molecules exist that bind and inhibit adiponectin function, contributing to adiponectin resistance and diabetic vascular injury. METHODS: Adult rats were randomly assigned to receive either a normal or a high-fat diet for 8 weeks. Plasma was co-immunoprecipitated with anti-APN antibody and analyzed by mass spectrometry. The APN binding molecules and their effect upon APN biological activity were determined. RESULTS: As expected, the high-fat-diet increased plasma triglyceride, total cholesterol, and low-density lipoprotein. Importantly, the circulating APN level was significantly increased at this time point. Mass spectrometry identified 18 proteins with increased APN binding in hyperlipidemic plasma, among which four proteins critical in lipid metabolism, including apolipoprotein A1 (APOA1), APOA4, APOC1, and paraoxonase 1, were further investigated. Incubating recombinant APN with APOA1 markedly (P < 0.01), and incubating with APOC1 significantly (P < 0.05), inhibited APN activity as evidenced by the reduced AMPK activation in HUVECs. APOA4 and paraoxonase 1 incubation had no effect upon APN activity. Finally, plasma APOA1 was significantly increased (P < 0.05) in hyperlipidemic plasma compared with the control plasma. CONCLUSIONS: It was demonstrated for the first time that increased APOA1 and APOC1 in hyperlipidemic plasma binds and inhibits APN activity. This result not only identifies a novel molecular mechanism responsible for adiponectin resistance during early stage diabetes, but also provides additional new insight into the diverse/controversial (protective and harmful) functions of high-density lipoprotein.
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Adiponectina , Arildialquilfosfatasa , Hiperlipidemias , Adiponectina/sangre , Animales , Arildialquilfosfatasa/sangre , Arildialquilfosfatasa/metabolismo , Dieta Alta en Grasa , Hiperlipidemias/sangre , Metabolismo de los Lípidos , Distribución Aleatoria , RatasRESUMEN
OBJECTIVES: Oxidative stress, induced by physical activity, may stimulate the expression, release, and activity of certain antioxidant enzymes. We investigated the effect of three repeated bouts of strenuous exercise on paraoxonase 1 concentration (PON1c) and paraoxonase activity (PON). METHODS: Eleven average-trained healthy men (age 34.0 ± 5.2 years) performed three strenuous exercise tests on a treadmill separated by 72 hours periods of resting. PON1c, PON, ferric-reducing activity of plasma (FRAP), lipid profile, C-reactive protein concentration (CRP), and lactate concentration were determined in plasma. RESULTS: Each exercise bout resulted in similar PON1c, PON, FRAP, and high-density lipoprotein concentration (HDL-C) increments, while PON/HDL-C ratio remained stable in all repetitions. Percentage increments at the bout of each exercise were higher for PON1c (by 64.82% at the first, by 92.9% at the second, and by 77.02% at the third exercise) than for PON (by 6.49% at the first, 10.06% at the second, and by 12.32% at the third exercise). Association was found between preexercise PON and PON1c (r = 0.56, p = 0.029), pre- (r = 0.87, p = 0.00003) and postexercise HDL-C (r = 0.6, p = 0.0002), preexercise PON and cardiovascular fitness level of participants measured as VO2max (r = 0.39, p = 0.026), and postexercise PON and lactate concentration (r = 0.44, p = 0.01). CONCLUSIONS: PON1c and PON increase during strenuous exercise, yet the effect of exercise on PON1 concentration is more pronounced. PON1 does not show tolerance to physical activity. The enzyme may provide short-term protection from oxidative stress in each exercise bout. PON may depend on exercise load. Cardiovascular fitness levels may be associated with PON1 activity.
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Arildialquilfosfatasa/sangre , Ejercicio Físico , Estrés Oxidativo , Descanso/fisiología , Adulto , Humanos , MasculinoRESUMEN
BACKGROUND: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. PATIENTS AND METHODS: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. RESULTS: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p < 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p < 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p < 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). CONCLUSIONS: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.
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Artritis Reumatoide/tratamiento farmacológico , Proteína C-Reactiva/metabolismo , Obesidad/tratamiento farmacológico , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/genética , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Artritis Reumatoide/metabolismo , Arildialquilfosfatasa/sangre , Biomarcadores/sangre , Hidrolasas de Éster Carboxílico/sangre , Grosor Intima-Media Carotídeo , Certolizumab Pegol/administración & dosificación , Etanercept/administración & dosificación , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Peroxidasa/sangre , Espondilitis Anquilosante/sangre , Espondilitis Anquilosante/complicaciones , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
The COVID-19 pandemic caused by SARS-CoV-2 challenges the understanding of factors affecting disease progression and severity. The identification of prognostic biomarkers and physiological processes associated with disease symptoms is relevant for the development of new diagnostic and therapeutic interventions to contribute to the control of this pandemic. To address this challenge, in this study, we used a quantitative proteomics together with multiple data analysis algorithms to characterize serum protein profiles in five cohorts from healthy to SARS-CoV-2-infected recovered (hospital discharge), nonsevere (hospitalized), and severe [at the intensive care unit (ICU)] cases with increasing systemic inflammation in comparison with healthy individuals sampled prior to the COVID-19 pandemic. The results showed significantly dysregulated proteins and associated biological processes and disorders associated to COVID-19. These results corroborated previous findings in COVID-19 studies and highlighted how the representation of dysregulated serum proteins and associated BPs increases with COVID-19 disease symptomatology from asymptomatic to severe cases. The analysis was then focused on novel disease processes and biomarkers that were correlated with disease symptomatology. To contribute to translational medicine, results corroborated the predictive value of selected immune-related biomarkers for disease recovery [Selenoprotein P (SELENOP) and Serum paraoxonase/arylesterase 1 (PON1)], severity [Carboxypeptidase B2 (CBP2)], and symptomatology [Pregnancy zone protein (PZP)] using protein-specific ELISA tests. Our results contributed to the characterization of SARS-CoV-2-host molecular interactions with potential contributions to the monitoring and control of this pandemic by using immune-related biomarkers associated with disease symptomatology.
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COVID-19/sangre , COVID-19/inmunología , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , Arildialquilfosfatasa/sangre , Biomarcadores/sangre , Carboxipeptidasa B2/sangre , Femenino , Humanos , Interleucina-1/sangre , Interleucina-4/sangre , Masculino , Persona de Mediana Edad , Proteínas Gestacionales/sangre , Pronóstico , Proteoma/análisis , Proteómica , Estudios Retrospectivos , Selenoproteína P/sangreRESUMEN
BACKGROUND: Acute and chronic besnoitiosis in extensive natural-service herds can have relevant effects in the health of bulls and negative consequences in their productive performance. Recent progress has been made in order to elucidate the pathogenesis of this disease. In this context, the study of biomarkers of inflammation in serum would contribute to gaining knowledge about the physiopathology of bovine besnoitiosis. Serological biomarkers could help in early diagnosis and prognosis, as seropositive bulls may have mild or severe testicular lesions. METHODS: Herein, we have investigated the diagnostic and/or prognostic value of a panel of serum (serological) biomarkers related to inflammation, including total protein, globulin and albumin, haptoglobin (Hp), adenosine deaminase (ADA) paraoxonase-1 (PON-1) and acetylcholinesterase (AChE) in naturally and experimentally B. besnoiti-infected males classified according to different clinical phases of the disease (acute, chronic and subclinical besnoitiosis). RESULTS: Results showed a similar response pattern in these biomarkers for naturally and experimentally infected cattle, with a few relevant variations. Most significant changes occurred during the acute phase of infection, although significant changes in a few biomarkers were also observed during the chronic infection. Haptoglobin, albumin, PON-1 and ADA were identified as the biomarkers that showed changes of higher magnitude in the acute phase of the infection, whereas high total protein and globulin values were found in chronically infected cattle. We have described the changes of a panel of inflammatory biomarkers of acute and chronic bovine besnoitiosis. CONCLUSIONS: In summary, several biomarkers with promising diagnostic value have been identified. The biomarkers associated with acute infection are related to previously reported molecular biomarkers in testicular parenchyma of infected bulls and could help in the diagnosis of early infections and complement results from specific immunoglobulin M (IgM) detection.