Usefulness of the Measurement of Serum Paraoxonase-1 Arylesterase Activity in the Diagnoses of COVID-19.

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.

Evaluation of Interleukin 6(Il-6), Tumor Necrosis Factor Alpha (Tnf-α) and Paraoxonase 1(Pon 1) in Obese and Non-Obese Metabolic Syndrome.

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.

Dynamic personalized risk prediction in chronic heart failure patients: a longitudinal, clinical investigation of 92 biomarkers (Bio-SHiFT study).

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 .

Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis: Associations with Vascular Pathophysiology.

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.

Changes in serum biomarkers of inflammation in bovine besnoitiosis.

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.

Association between inflammatory markers and serum paraoxonase and arylesterase activities in the general population: a cross-sectional study.

BACKGROUND: Recent studies focused on modulating factors of paraoxonase-1 (PON1) activity. In some studies the association between pro-inflammatory markers and PON1 activity was examined, but so far no population-based investigations on this issue have been conducted. The present study investigated the relationships between the pro-inflammatory markers tumor necrosis factor (TNF)-α, leptin, interleukin (IL)-6, and high-sensitive C-reactive protein (hs-CRP) and paraoxonase and arylesterase, two hydrolytic activities of PON1, in the population-based Bavarian Food Consumption Survey II. METHODS: Based on 504 participants (217 men, 287 women), the relationship between the pro-inflammatory markers and the outcomes paraoxonase and arylesterase activities were investigated using multivariable linear models. RESULTS: Circulating plasma levels of leptin (P-value < 0.0001), hs-CRP (P-value = 0.031) and IL-6 (P-value = 0.045) were significantly non-linearly associated with arylesterase activity. Leptin levels were also significantly associated with paraoxonase activity (P-value = 0.024) independently from confounding factors, including high-density lipoprotein (HDL) cholesterol. With increasing levels of these inflammatory parameters, arylesterase and paraoxonase activities increased; however, at higher levels (> 75th percentile) the activities reached a plateau or even decreased somewhat. After Bonferroni-Holm correction, only leptin remained non-linearly but significantly associated with arylesterase activity (adjusted overall P-value < 0.0001). Neither age nor sex nor obesity modified the associations. No association was found between TNF-α and paraoxonase or arylesterase activity. CONCLUSIONS: The present findings suggest that in persons with very high levels of inflammation, PON1 activity may be impaired, a fact that might subsequently be accompanied by a higher risk for cardiometabolic diseases. Whether or not the measurement of PON1 activity in combination with a lipid profile and certain inflammatory markers could improve the prediction of cardiometabolic diseases in middle-aged individuals from the general population should be evaluated in clinical studies.

Paraoxonase (PON)-1 activity in septic neonates: One more arrow in the quiver of biomarkers of neonatal sepsis?

Paraoxonase-1 (PON-1), a calcium ion-dependent high-density lipoprotein (HDL)-associated enzyme, has been proposed as a negative acute phase reactant biomarker in animal and human adult studies. The aim of this study was to evaluate the value of PON-1 activity in the diagnosis and monitoring of neonatal sepsis. Serum PON-1 activity, as paraoxonase and arylesterase, was prospectively studied in 48 septic neonates and matched controls. PON-1 activity was decreased at the acute phase of sepsis in comparison with values at recovery and values in controls. Paraoxonase or arylesterase at enrollment correlated significantly with serum Amyloid-A, CRP and IL-6 and could also discriminate septic than non-septic neonates. In conclusion, our results are promising regarding the role of PON-1 as a biomarker of neonatal sepsis. Larger studies are needed to validate the clinical utility of PON-1 in neonatal medicine.

Combination of serum paraoxonase/arylesterase 1 and antithrombin-III is a promising non-invasion biomarker for discrimination of AFP-negative HCC versus liver cirrhosis patients.

OBJECTIVE: α-fetoprotein is often used in the diagnosis of hepatocellular carcinoma (HCC). However, there are currently less efficient and highly specific biomarkers to distinguish AFP-negative HCC from liver cirrhosis (LC) patients. PATIENTS AND METHODS: We retrospectively analyzed the data of patients who were treated in our hospitals. iTRAQ coupled with mass spectrometry was used to identify candidate serum proteins in a discovery set (n = 36) including AFP-negative HCC and LC patients. After Western blot detection, potential serum biomarkers were confirmed using ELISA in a validation set (n = 90). The diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC). RESULTS: PON1 and ATIII were selected as target proteins and were significantly higher in LC than those in AFP-negative HCC patients as validated by Western blot and ELISA, which was consistent with the result of iTRAQ. The AUC was 0.848 as PON1 and ATIII were combined (sensitivity: 80.0%; specificity: 73.3%), and performed much better than that of a single biomarker. CONCLUSION: These findings suggest that PON1 and ATIII have the potential to serve as effective biomarkers for distinguishing AFP-negative HCC from cirrhosis.

The role of proprotein convertase subtilisin/kexin type-9 concentration and paraoxonase 1 activities in the blood of women with polycystic ovary syndrome.

This study aimed to evaluate the concentration of proprotein convertase subtilisin/kexin type-9 (PCSK9) and the activities of paraoxonase 1 in women with and without polycystic ovary syndrome (PCOS). We found significant higher PCSK9, whereas lower high-density lipoprotein concentration in the serum of women with PCOS when compared to the group without PCOS. Also paraoxonase 1 activities were significantly different between women with PCOS than without PCOS. In addition, the women with PCOS and insulin resistance had higher concentrations of PCSK9 than women with PCOS and insulin sensitivity. Higher PCSK9 concentration in the group with PCOS could be also associated with hormones concentrations. Changes in paraoxonase 1 activities and lipid profile parameters as well as higher concentration of PCSK9 in the group of women with PCOS could be associated with metabolism disorders, but due to the small clinical sample size, the study should be continued.

Altered high-density lipoprotein composition and functions during severe COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.

Possible Reduction of Cardiac Risk after Supplementation with Epigallocatechin Gallate and Increase of Ketone Bodies in the Blood in Patients with Multiple Sclerosis. A Pilot Study.

Multiple sclerosis (MS) is a neurodegenerative disease that causes anthropometric changes characterised by functional disability, increase in fat mass, and decrease in lean mass. All these variables are related to a greater cardiac risk. The polyphenol epigallocatechin gallate (EGCG) and an increase in ketone bodies in the blood have been shown to have beneficial effects on anthropometric and biochemical variables related to cardiovascular activity. The aim of this study was to analyse the impact of the intervention with EGCG and ketone bodies on cardiac risk in MS patients. A population of 51 MS patients were randomly assigned to a control group and an intervention group (daily dose of 800 mg of EGCG and 60 mL of coconut oil). Both groups followed an isocaloric diet for 4 months. Levels of beta-hydroxybutyrate (BHB), albumin, paraoxonase 1 (PON1) and C-reactive protein (CRP) were measured in serum before and after the intervention, as well as determining functional ability, waist circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and muscle percentage. After 4 months, in the intervention group there was a significant increase in BHB, PON1 and albumin, while CRP did not vary; a significant decrease in cardiac risk associated with a significant decline in WHR; as well as a significant increase in muscle percentage. By contrast, these changes were not observed in the control group. Finally, results from analysis of variance (ANOVA) revealed a significant time-condition interaction effect, observing that WHtR and fat mass decreased in the intervention group, while they increased in the control group.

Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Restores PON1 Activity.

Atheroprotective functions of high-density lipoproteins (HDL) are related to the activity of HDL-associated enzymes such as paraoxonase 1 (PON1). We examined the impact of inhibition of myeloperoxidase (MPO)-mediated HDL oxidation by PON1 on HDL malondialdehyde (MDA) content and HDL function. In the presence of PON1, crosslinking of apoAI in response to MPO-mediated oxidation of HDL was abolished, and MDA-HDL adduct levels were decreased. PON1 prevented the impaired cholesterol efflux capacity of MPO-oxidized HDL from Apoe-/- macrophages. Direct modification of HDL with MDA increased apoAI crosslinking and reduced the cholesterol efflux capacity. MDA modification of HDL reduced its anti-inflammatory function compared to native HDL. MDA-HDL also had impaired ability to increase PON1 activity. Importantly, HDL from subjects with familial hypercholesterolemia (FH-HDL) versus controls had increased MDA-apoAI adducts, and PON1 activity was also impaired in FH. Consistently, FH-HDL induced a pro-inflammatory response in Apoe-/- macrophages and had an impaired ability to promote cholesterol efflux. Interestingly, reactive dicarbonyl scavengers, including 2-hydroxybenzylamine (2-HOBA) and pentyl-pyridoxamine (PPM), effectively abolished MPO-mediated apoAI crosslinking, MDA adduct formation, and improved cholesterol efflux capacity. Treatment of hypercholesterolemic mice with reactive dicarbonyl scavengers reduced MDA-HDL adduct formation and increased HDL cholesterol efflux capacity, supporting the therapeutic potential of reactive carbonyl scavenging for improving HDL function.

Serum paraoxonase 1 and 3 activities in benign and malignant diseases of the prostate and changes in levels following robotic-assisted laparoscopic radical prostatectomy

Background/aim: This study aimed to examine serum paraoxonase 1 and 3 (PON1 and PON3) activities in benign and malignant diseases of the prostate, to determine lipid profile and malondialdehyde (MDA) levels, and to investigate changes in levels following robotic-assisted laparoscopic radical prostatectomy (RALRP). Materials and methods: A total of 137 patients, including a control group, were enrolled in the study and assigned into four groups. Group 1 (n = 33) consisted of patients previously undergoing RALRP with no recurrence, group 2 (n = 36) consisted of patients diagnosed with prostate cancer (PCa) and undergoing RALRP, and group 3 (n = 34) consisted of patients diagnosed with benign prostatic hyperplasia. The control group (n = 34) consisted of healthy individuals. Serum low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, cholesterol, prostate-specific antigen (PSA), PON1, PON3, and MDA values were measured. In addition, group 2 MDA, PON1, PON3, and PON1/HDL levels were investigated preoperatively and at the first month postoperatively. Results: Significant changes were found in PON1, PON3, and MDA levels. PON1 and PON3 levels decreased significantly in patients with PCa, while MDA levels increased. PON1 and PON3 increased postoperatively in the PCa group, while MDA decreased. BPH group PON1, PON3, and MDA levels were higher than those of the control group. Conclusion: An increase in free oxygen radicals in the body or a decrease in endogenous antioxidant enzyme levels can result in malignant and benign diseases of the prostate. Surgical excision of malignant tissue in PCa causes a decrease in oxidative stress.

Bariatric surgery decreases oxidative stress and protein glycosylation in patients with morbid obesity.

BACKGROUND: There is growing evidence that oxidative stress (OS) is a critical factor linking obesity with its associated comorbidities, such as cardiovascular diseases. AIM: To evaluate the degree of OS in people with morbid obesity and its relationship with glycoproteins, determined using 1H-NMR spectroscopy, before and after bariatric surgery (BS). METHODS: In this observational cohort study, plasma from 24 patients with BMI ≥ 40 kg/m2 (age: 21-65 years) was used to measure metabolites implicated in OS. We measured glycoprotein (GlycA, GlycB and GlycF) areas and shape factors (H/W = height/width). RESULTS: One year after BS, oxidized low-density lipoprotein had decreased by 49% (P < .0001), malondialdehyde by 32% (P = .0019) and lipoprotein (a) by 21% (P = .0039). The antioxidant enzymes paraoxonase-1 and catalase increased after BS (43%, P < .0001 and 54%, P = .0002, respectively). Superoxide dismutase-2 had fallen 1 year after BS (32%, P = .0052). After BS, both the glycoprotein areas and shape factors decreased by 20%-26%. These glycoproteins were significantly correlated with OS parameters. The plasma atherogenic index was 63% higher in obese individuals than 1 year after BS and correlated positively with glycoproteins. CONCLUSION: For the first time, we here demonstrate the relationship between OS parameters and glycoproteins in people with morbid obesity. So glycoproteins could therefore be a good indicator, together with the oxidative state to assess patient prognosis after BS.

Polycystic ovary syndrome and endothelial dysfunction: A potential role for soluble lectin-like oxidized low density lipoprotein receptor-1.

The aims of this study were to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), oxidized LDL (oxLDL), paraoxonase-1(PON-1) and hydroperoxide (LOOH) levels are altered in women with polycystic ovary syndrome (PCOS) and also to determine if hyperandrogenism, insulin resistance (IR) and Anti-Müllerian Hormone (AMH) are associated with endothelial dysfunction in PCOS. A total of 46 women with PCOS and 46 non-PCOS healthy controls were recruited. Women with PCOS had significantly higher sLOX-1, oxLDL and LOOH concentrations than non-PCOS women [6.16 (3.92-13.95) vs 1.37 (0.63-4.43) ng/mL, p < 0.001; 6.48 ± 1.03 vs 3.16 ± 1.02 µU/L, p < 0.001; 2.45 (1.45-3.45) vs 1.06 (0.64-1.56) µmol/L, p < 0.001]. The mean PON-1 level of PCOS group was lower than non-PCOS group (69.47 ± 10.75 vs 104.08 ± 21.43 U/mL, p < 0.001). There was no significant difference in terms of the sLOX-1, oxLDL, LOOH and PON-1 levels between normal weight and overweight PCOS women. On univariate logistic regression analysis, Ferriman-Gallwey scale (FGS), HOMA-IR and AMH were an independent predictors of high risk group of endothelial dysfunction markers (HR-EDm). Age and BMI were not associated with HR-EDm. When incorporated into the multivariate model, endotelial dysfunction markers independently correlated with clinical hyperandrogenism (FGS) but not with AMH. In conclusion, our results indicated that an increased concentration of sLOX-1 might be an early predictor of endothelial damage in patients with PCOS. Women with PCOS have elevated sLOX-1, oxLDL, LOOH and decreased PON-1 levels, independent of BMI. Endothelial dysfunction in women with PCOS is associated with hyperandrogenism. Further studies are required to confirm our findings.

The Relation between Eating Habits and Abdominal Fat, Anthropometry, PON1 and IL-6 Levels in Patients with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurodegenerative disease of an inflammatory, demyelinating and autoimmune nature. Diets with a high caloric density could be especially relevant in terms of the pathogenesis related to an increase in adipose tissue that is metabolically active and releases mediators, which can induce systemic inflammation and an increased oxidation state. The aim of this study was to analyse the eating habits related to calorie intake and their impact on abdominal obesity associated with anthropometric variables, the activity of the oxidation marker paraoxonase 1 (PON1), and interleukin 6 (IL-6) levelsin MS patients. METHODS: An analytical and quantitative observational study was conducted with a population of 57 MS patients. The dietary-nutritional anamnesis was gained through the Food Frequency Questionnaire and a food diary. Diet and eating habits have been analysed through the Easy Diet-Programa de gestión de la consulta® software. Anthropometric measurements were taken in order to determine the presence of abdominal obesity. In addition, PON1 was quantified in serum by means of automated spectrophotometric assays and IL-6 was quantified using the ELISA technique. RESULTS: A normal calorie intake was determined for women, yet a slightly lower intake was observed in men. Carbohydrate consumption was below what was established, and protein and lipids were over, in both cases. Furthermore, most patients had abdominal obesity, with significantly higher body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and IL-6 levels. IL-6 is greatly correlated with waist circumference and WHtR. CONCLUSION: MS patients' nutrient intake shows an imbalance between macronutrients. This seems to favour the abdominal obesity associated with high values of proinflammatory IL-6 that is not correlated with a lower activity of PON1.

Identification of Protein Expression Changes in Hepatocellular Carcinoma through iTRAQ.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor associated with a poor prognosis. Serum biomarkers of HCC have the potential to improve the diagnosis, provide a means to monitor the tumors, and predict their malignancy. Proteins that are expressed differentially between HCC patients and normal controls have the potential to be biomarkers. METHOD: Serum samples from 10 confirmed HCC patients and 10 controls were collected. The differentially expressed proteins in the serum were identified using an isobaric tags for relative and absolute quantitation- (iTRAQ-) based method. Potential serum biomarkers were validated by ELISA in another 20 HCC patients and 20 controls. Their expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. RESULTS: A total of 260 proteins were measured in the serum of HCC patients and compared to those in sex- and age-matched normal controls. Forty-one proteins displayed significant changes, with 26 being downregulated and 15 being upregulated. Upregulated proteins included alpha-1-antitrypsin (A1AT) and peroxiredoxin 2 (PRDX2), and downregulated proteins included paraoxonase 1 (PON1) and C-reactive protein (CRP). We then used ELISA to measure serum levels of A1AT, PRDX2, PON1, and CRP in another 20 patients with HCC and found that only PON1 levels were consistent with the iTRAQ result. In TCGA dataset, PON1 expression was downregulated in HCC tissues (P < 0.001) and low expression of PON1 was associated with poor survival in HCC patients (P < 0.001) and low expression of PON1 was associated with poor survival in HCC patients (. CONCLUSIONS: PON1 could act as a biomarker for HCC to assist in the diagnosis of HCC.

Molecular Docking Studies and Inhibition Properties of Some Antineoplastic Agents against Paraoxonase-I.

BACKGROUND: Currently, most of the drugs used in clinical applications show their pharmacological influences by inhibiting or activating enzymes. Therefore, enzyme inhibitors have an essential place in the drug design for many diseases. OBJECTIVE: The current study aimed to contribute to this growing drug design field (i.e., medicine discovery and development) by analyzing enzyme-drug interactions. METHODS: For this reason, Paraoxonase-I (PON1) enzyme was purified from fresh human serum by using rapid chromatographic techniques. Additionally, the inhibition effects of some antineoplastic agents were researched on the PON1. RESULTS: The enzyme was obtained with a specific activity of 2603.57 EU/mg protein. IC50 values for pemetrexed disodium, irinotecan hydrochloride, dacarbazine, and azacitidine were determined to be 9.63µM, 30.13µM, 53.31µM, and 21.00mM, respectively. These agents found to strongly inhibit PON1, with Ki constants ranging from 8.29±1.47µM to 23.34±2.71mM. Dacarbazine and azacitidine showed non-competitive inhibition, while other drugs showed competitive inhibition. Furthermore, molecular docking was performed using maestro for these agents. Among these, irinotecan hydrochloride and pemetrexed disodium possess the binding energy of -5.46 and -8.43 kcal/mol, respectively. CONCLUSION: The interaction studies indicated that these agents with the PON1 possess binding affinity.

Cardiovascular evaluation and serum paraoxonase-1 levels in adolescents with polycystic ovary syndrome.

The aim of our study was to evaluate whether cardiovascular disease risks seen in adults with polycystic ovary syndrome (PCOS) develop in adolescents with PCOS using conventional Doppler echocardiography (CDE) and tissue Doppler echocardiography (TDE) or not. The other aim was to investigate the association of paraoxonase-1 (PON-1) level with cardiovascular parameters. 30 PCOS patients and 30 control patients were included in the study. All patients were evaluated with TDE and CDE. Paraoxonase-1 levels of both groups were studied. In CDE study, myocardial performance index (MPI) was higher in the PCOS group than in the control group (0.54 ± 0.11, 0.50 ± 0.12, p = .049, respectively). In the TDE study, early diastolic myocardial velocity (E)'/late diastolic myocardial velocity (A') was lower in PCOS group than in the control group (2.07 ± 0.08, 2.44 ± 0.10, p = .008, respectively). PON-1 was higher in PCOS group than in the control group (26.81 ± 3.05, 18.68 ± 1.18, p = .011, respectively). Cardiovascular disease risks, which are among the long-term complications of PCOS, seem to begin from the early stage of PCOS. The high PON-1 level was thought to increase in response to increased oxidative stress in PCOS.Impact statementWhat is already known on this subject? Polycystic ovary syndrome (PCOS) is one of the most commonly seen endocrinopathy in the adolescent age group. PCOS has detrimental effects on the cardiovascular system in the adult population which is reported in many studies.What the results of this study add? The result of this study showed that cardiovascular effects, which are among the long-term complications of PCOS, seem to begin from the early stage of PCOS. And also, serum paraoxonase-1 level increases in response to the oxidative stress in the adolescent with PCOS.What are the implications of these findings for clinical practice and/or further research? The cardiovascular system evaluation should be started in early phases of PCOS development in the adolescent age group. The potential role of oxidative effect of Paraoxonase-1 on the PCOS needs to be elucidated in further studies.

Intravenous laser wavelength radiation effect on LCAT, PON1, catalase, and FRAP in diabetic rats.

The main purpose of this study is to evaluate the effect of intravenous irradiation of different low-level laser wavelengths on the activity of lecithin-cholesterol acyltransferase (LCAT), paraoxonase (PON1), catalase, and ferric reducing ability of plasma (FRAP) in diabetic rats. First, diabetes was induced in rats using streptozotocin (STZ). Enzymes' activity was measured in the blood samples and compared before and after intravenous laser blood irradiation. We used four continuous-wave lasers-IR (λ = 808 nm), Red (λ = 638 nm), Green (λ = 532 nm), and Blue (λ = 450 nm)-to compare the wavelength's effect on different enzymes' activity. Laser power was fixed at 0.01 mW and laser energy was changed by 2-, 4-, 6-, and 8-min time of radiations.The enzymes' activity of blood samples was measured 2, 6, and 24 h after radiation. The results show an increase in the activity of different enzymes when compare with diabetic non-radiated samples. More importantly, with a constant laser energy, the enzymes' activity increased with decreasing laser wavelength. It is important to note that with a constant laser energy, as the wavelength decreases, the photon energy increases and the number of photons decrease, while the enzyme's activity elevation increases. As a result, we can conclude that in intravenous low-level laser therapy, photon energy is more important than the number of photons even if their product, energy, is kept constant.