Paraoxonase Research Articles

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats.

A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•-) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters.

Can HDL cholesterol be replaced by paraoxonase 1 activity in the prediction of severe coronary artery disease in patients with type 2 diabetes?

Background and aimsNovel biomarkers are required to improve cardiovascular disease prediction in patients with type 2 diabetes (T2D) as a high-risk population. This study was conducted to examine whether coronary artery disease (CAD) risk assessment can be improved by substituting high-density lipoprotein (HDL)-bound paraoxonase 1 (PON1) activity for HDL cholesterol (HDL-C) concentration in patients with T2D. Methods and resultsIn this study, we studied 139 patients with T2D (mean age 64.12 ± 8.17 years) who underwent coronary angiographic examination. The initial rate of substrate hydrolysis was spectrophotometrically assayed in kinetic mode for measuring PON1 activity. Receiver operating characteristic (ROC) graphs are created by plotting true positivity versus false positivity. In patients with HbA1c ≥ 7%, PON1 (AUC = 0.7, p = 0.029) and nonHDL-C/PON1 (AUC = 0.75, p = 0.013) were significantly more capable of differentiating patients with CAD from those without CAD compared to HDL-C and nonHDL-C/HDL-C. Also, the predictive power of PON1 (AUC = 0.64, p = 0.029) and nonHDL-C/PON1 (AUC = 0.71, p = 0.004) were significantly higher in comparison with HDL-C and nonHDL-C/HDL-C for CAD characterization in patients aged ≥50 years. Moreover, PON1 and nonHDL-C/PON1 are associated with the incidence of CAD with an AUC of 0.7 (p = 0.026) and AUC of 0.64 (p = 0.087), respectively, among subjects with low HDL-C. ConclusionPON1 and the ratio of nonHDL-C/PON1 significantly improve the prediction of severe CAD in T2D patients and in patients with HbA1c ≥ 7%, age ≥50 years, or low HDL-C. PON1 activity and lipid ratios using this enzyme may be valuable as substitutes of HDL-C for increasing clinical efficacies in cardiovascular risk assessment.

Vitamin E intake and paraoxonase 1 (PON1) rs662 genetic polymorphism are associated with colorectal cancer risk in a Korean population

Vitamin E and paraoxonase 1 (PON1) are associated with cancer development. However, their interactive effect on colorectal cancer (CRC) risk is inconclusive. We conducted a case–control study including 1,351 CRC patients and 2,670 controls at the Korean National Cancer Centre (KNCC). There was an inverse association between vitamin E intake and CRC risk (odds ratio (OR) = 0.31; 95% confidence interval (CI) = 0.22–0.42). We identified a reduced CRC risk among individuals with CC genotype of PON1 rs662 polymorphism compared with subjects carrying the T allele (OR = 0.74; 95% CI = 0.61–0.90). The highest interaction between vitamin E intake and PON1 rs662 variants was significant for the subjects carrying the CC genotype (p-interaction = 0.014). This study provided further supporting evidence that vitamin E intake is associated with lower odds of CRC. Furthermore, the activity of vitamin E is strengthened among individuals carrying C allele of the PON1 rs662 polymorphism.

Protective effect of melatonin and ascorbic acid combination on sepsis-induced lung injury: An Experimental study.

This study investigated the synergistic protective effects of melatonin (MEL) and ascorbic acid (vitamin C, ASA) in treating sepsis-induced lung injury in rats. Rats were divided into five groups: control, cecal ligation and puncture (CLP), CLP + MEL, CLP + ASA and CLP + MEL + ASA. The effects of MEL (10 mg/kg), ASA (100 mg/kg) and their combination on oxidative stress, inflammation and histopathology were evaluated in septic rats' lung tissues. Sepsis-induced oxidative stress and inflammation were evident through increased levels of malondialdehyde (MDA), myeloperoxidase (MPO), total oxidant status (TOS)and oxidative stress index (OSI); decreased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx); and elevated levels of tumour necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) in the lung tissue. Treatment with MEL, ASA and their combination significantly improved antioxidant capacity and reduced oxidative stress, with the combination treatment being more effective. The combination treatment also significantly reduced TNF-α and IL-1β levels and improved peroxisome proliferator-activated receptor (PPAR), arylesterase (ARE) and paraoxonase (PON) levels in the lung tissue. Histopathological examination showed reduced oedema and lymphocyte infiltration with a lung tissue appearance similar to the control group. Immunohistochemical staining for caspase 3 demonstrated reduced immune positivity in the treatment groups. In conclusion, this study supports the potential synergistic protective effects of MEL and ASA in treating sepsis-induced lung injury. The combination therapy could effectively reduce oxidative stress, inflammation and improve antioxidant capacity in septic rats, suggesting a promising strategy for treating sepsis-induced lung injury.

Paraoxonase-1: How a xenobiotic detoxifying enzyme has become an actor in the pathophysiology of infectious diseases and cancer

Both infectious and non-infectious diseases can share common molecular mechanisms, including oxidative stress and inflammation. External factors, such as bacterial or viral infections, excessive calorie intake, inadequate nutrients, or environmental factors, can cause metabolic disorders, resulting in an imbalance between free radical production and natural antioxidant systems. These factors may lead to the production of free radicals that can oxidize lipids, proteins, and nucleic acids, causing metabolic alterations that influence the pathogenesis of the disease. The relationship between oxidation and inflammation is crucial, as they both contribute to the development of cellular pathology. Paraoxonase 1 (PON1) is a vital enzyme in regulating these processes. PON1 is an enzyme that is bound to high-density lipoproteins and protects the organism against oxidative stress and toxic substances. It breaks down lipid peroxides in lipoproteins and cells, enhances the protection of high-density lipoproteins against different infectious agents, and is a critical component of the innate immune system. Impaired PON1 function can affect cellular homeostasis pathways and cause metabolically driven chronic inflammatory states. Therefore, understanding these relationships can help to improve treatments and identify new therapeutic targets. This review also examines the advantages and disadvantages of measuring serum PON1 levels in clinical settings, providing insight into the potential clinical use of this enzyme.

Role of paraoxonase 1 activity and PON1 gene polymorphisms in sickle cell disease

Sickle cell disease (SCD) patients often exhibit a dyslipidemic sub-phenotype. Paraoxonase 1 (PON 1) is a serum glycoprotein associated with the high-density lipoproteins cholesterol (HDL-C), and variability in PON1 activity depends on the PON1 genotypes. We investigated the influence of PON1c.192Q > R and PON1c.55L > M polymorphisms on PON1 activity and laboratory parameters and the association between PON1 activity and clinical manifestations in SCD patients. We recruited 350 individuals, including 154 SCD patients and 196 healthy volunteers, which comprised the control group. Laboratory parameters and molecular analyses were investigated from the participants' blood samples. We have found increased PON1 activity in SCD individuals compared to the control group. In addition, carriers of the variant genotype of each polymorphism presented lower PON1 activity. SCD individuals carrying the variant genotype of PON1c.55L > M polymorphism had lower platelet and reticulocyte counts, C-reactive protein, and aspartate aminotransferase levels; in addition to higher creatinine levels. SCD individuals carrying the variant genotype of PON1c.192Q > R polymorphism had lower triglyceride, VLDL-c, and indirect bilirubin levels. Furthermore, we observed an association between PON1 activity history of stroke and splenectomy. The present study confirmed the association between PON1c.192Q > R and PON1c.55L > M polymorphisms and PON1 activity, in addition to demonstrate their effects on markers of dislipidemia, hemolysis and inflammation, in SCD individuals. Moreover, data suggest PON1 activity as a potential biomarker related to stroke and splenectomy.

Reduction of Paraoxonase Expression Followed by Inactivation across Independent Semiaquatic Mammals Suggests Stepwise Path to Pseudogenization.

Convergent adaptation to the same environment by multiple lineages frequently involves rapid evolutionary change at the same genes, implicating these genes as important for environmental adaptation. Such adaptive molecular changes may yield either change or loss of protein function; loss of function can eliminate newly deleterious proteins or reduce energy necessary for protein production. We previously found a striking case of recurrent pseudogenization of the Paraoxonase 1 (Pon1) gene among aquatic mammal lineages-Pon1 became a pseudogene with genetic lesions, such as stop codons and frameshifts, at least four times independently in aquatic and semiaquatic mammals. Here, we assess the landscape and pace of pseudogenization by studying Pon1 sequences, expression levels, and enzymatic activity across four aquatic and semiaquatic mammal lineages: pinnipeds, cetaceans, otters, and beavers. We observe in beavers and pinnipeds an unexpected reduction in expression of Pon3, a paralog with similar expression patterns but different substrate preferences. Ultimately, in all lineages with aquatic/semiaquatic members, we find that preceding any coding-level pseudogenization events in Pon1, there is a drastic decrease in expression, followed by relaxed selection, thus allowing accumulation of disrupting mutations. The recurrent loss of Pon1 function in aquatic/semiaquatic lineages is consistent with a benefit to Pon1 functional loss in aquatic environments. Accordingly, we examine diving and dietary traits across pinniped species as potential driving forces of Pon1 functional loss. We find that loss is best associated with diving activity and likely results from changes in selective pressures associated with hypoxia and hypoxia-induced inflammation.

INTERACTOME OF PARAOXONASE PON2 REVEALS NEW PATHWAYS FOR TUMOR GROWTH REGULATION

The interactome of paraoxonase-2 encoded by the PON2 gene was investigated. A cDNA library was screened using a yeast two-hybrid system to search for new proteins interacting with human PON2. Analysis of the identified candidates, along with previously published data on interactors obtained by other methods, indicates the presence of a significant number of indirect interactions between PON2 and EGFR and, consequently, possible regulation of tumor growth with mutant EGFR involving PON2.

Gastroprotective effects of bromelain on indomethacin-induced gastric ulcer in rats

Gastric ulcer is one of the most common diseases of the gastrointestinal system and some of its complications are the main causes of morbidity and mortality. Bromelain (BRM), a sulfhydryl proteolytic enzyme, has multiple activities in many areas of medicine as an antioxidant and anti-inflammatory agent. In this study, it was aimed to investigate the anti-inflammatory and oxidative stress-mediated therapeutic effect of BRM in a gastric ulcer model induced by indomethacin (IND) which is a non-steroidal anti-inflammatory drug (NSAID) with gastric ulcer-forming effects. Gastric mucosal paraoxonase (PON), arylesterase (ARE), catalase (CAT), myeloperoxidase (MPO) and glutathione peroxidase (GPx) activity and total glutathione (GSH) levels were analyzed. Interleukin-33 (IL-33), the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) levels were determined by immunohistochemically. Although IND-induced histopathological changes occurred, BRM pretreatment prevented these effects. As a result of the study, it was determined that BRM had an anti-ulcerative effect at a dose of 50 mg/kg. BRM given at this dose significantly decreased gastric tissue MPO activity, and increased CAT, PON, ARE, GPx activity and GSH level. The increased IL-33 and decreased Nrf-2 and HO-1 levels were obtained in IND group and these changes were reversed by BRM. As a result, it was concluded that BRM may have protective effects in IND-induced gastric model by reducing inflammation and regulating oxidant/antioxidant balance.

Desflurane Protects The Brain Against The Oxidant Activity of Acute Hyperglycemia in Diabetic Rats, Comparison with Sevoflurane

In this study, we investigated the effects of sevoflurane and desflurane administration on the oxidant and antioxidant system in the brain of acute hyperglycemia in diabetic rats. In the study, 30 male Wistar Albino rats were randomly divided into five groups. Diabetes was induced by administering a single dose of intraperitoneal streptozotocin (55 mg/kg) to rats except for the control group (C). To create acute hyperglycemia in diabetic groups, which were hyperglycemia (DH), desflurane (D), and sevoflurane (S) groups, 2.5 g/kg glucose was administered intraperitoneally. After glucose administration, desflurane 6% and sevoflurane 2.3% mixed with 4 L/min oxygen were administered for 2 hours, by which minimal alveolar concentration for rats would be one. Afterward, the animals were sacrificed, and their brain tissues were prepared for biochemical analysis. Catalase (CAT), glutathione-s-transferase (GST), paraoxonase (PON) activities, and TBARS levels were measured to determine oxidant and antioxidant status. GST activity was significantly lower in group D than in group DH (p=0.001). The PON activity was significantly lower in the D group compared with other groups (p<0.001). In the S group, PON activity was significantly lower than in the diabetic control (DC) group and DH groups (p=0.022, p=0.020, respectively). TBARS level was significantly lower in group D than in group DH (p=0.013). As a result, desflurane decreases GST and PON activity and TBARS levels more than sevoflurane. In terms of lipid peroxidation, desflurane shows more protective properties than sevoflurane. Since our study is the first study in this field, it should be supported by other studies to be carried out.

Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine-class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity.

Paraoxonase 1 (PON1) was purified 148.80-fold in 37.92% yield by hydrophobic interaction chromatography technique. The purity of PON1 was checked by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with a single band of 43kDa. The in vitro effects of nine different calcium channel blockers on PON1 activity were evaluated. All drugs strongly decreased PON1 activity, and IC50 levels were between 13.987 ± 0.59 and 238.104 ± 2.14μM, Ki values between 8.58±0.36 and 111±1.27μM. The drugs with the strongest inhibitory effect were nisoldipine with 13.987 ± 0.59μM and nicardipine with 20.158 ± 0.43μM. The mechanism of action for the inhibition of the enzyme by nisoldipine and nicardipine was investigated through molecular docking. The stability of enzyme-ligand complexes obtained from the docking was explored through molecular dynamics simulation. The binding affinity of the ligands toward the enzyme was also investigated through MMPBSA (molecular mechanics Poisson-Boltzmann surface area method). The computational analysis demonstrated these compounds could inhibit the enzyme. Nisoldipine had the strongest binding, and its complex was the most stable one. Furthermore, nicardipine was found to have the highest affinity toward the enzyme.

Proteomic Exploration of Paraoxonase 1 Function in Health and Disease.

High-density lipoprotein (HDL) exhibits cardio- and neuro-protective properties, which are thought to be promoted by paraoxonase 1 (PON1), a hydrolytic enzyme associated with an HDL subfraction also enriched with an anticoagulant protein (PROS1) and amyloid beta-transport protein clusterin (CLU, APOJ). Reduced levels of PON1 activity, characterized biochemically by elevated levels of homocysteine (Hcy)-thiolactone, oxidized lipids, and proteins modified by these metabolites in humans and mice, are associated with pathological abnormalities affecting the cardiovascular system (atherothrombosis) and the central nervous system (cognitive impairment, Alzheimer's disease). The molecular bases of these abnormalities have been largely unknown. Proteomic and metabolic studies over the past decade have significantly contributed to our understanding of PON1 function and the mechanisms by which PON1 deficiency can lead to disease. Recent studies discussed in this review highlight the involvement of dysregulated proteostasis in the pro-oxidative, pro-atherothrombotic, and pro-amyloidogenic phenotypes associated with low PON1 activity.

Vutiglabridin Modulates Paraoxonase 1 and Ameliorates Diet-Induced Obesity in Hyperlipidemic Mice.

Vutiglabridin is a clinical-stage synthetic small molecule that is being developed for the treatment of obesity and its target proteins have not been fully identified. Paraoxonase-1 (PON1) is an HDL-associated plasma enzyme that hydrolyzes diverse substrates including oxidized low-density lipoprotein (LDL). Furthermore, PON1 harbors anti-inflammatory and antioxidant capacities and has been implicated as a potential therapeutic target for treating various metabolic diseases. In this study, we performed a non-biased target deconvolution of vutiglabridin using Nematic Protein Organisation Technique (NPOT) and identified PON1 as an interacting protein. We examined this interaction in detail and demonstrate that vutiglabridin binds to PON1 with high affinity and protects PON1 against oxidative damage. Vutiglabridin treatment significantly increased plasma PON1 levels and enzyme activity but not PON1 mRNA in wild-type C57BL/6J mice, suggesting that vutiglabridin modulates PON1 post-transcriptionally. We further investigated the effects of vutiglabridin in obese and hyperlipidemic LDLR-/- mice and found that it significantly increases plasma PON1 levels, while decreasing body weight, total fat mass, and plasma cholesterol levels. Overall, our results demonstrate that PON1 is a direct, interacting target of vutiglabridin, and that the modulation of PON1 by vutiglabridin may provide benefits for the treatment of hyperlipidemia and obesity.

Mitigating heat stress in broiler chickens using dietary onion (Allium cepa) and ginger (Zingiber officinale) supplementation

The objective of this study was to evaluate the effect of dietary onion (Allium cepa) and ginger (Zingiber officinale) supplementation on growth, carcass quality, antioxidant status, and immune response in broilers under heat stress. A total of 700 day-old Hubbard broiler chicks were weighed and assigned to five treatments and five replicates. Broilers were maintained in a thermoneutral (TN) environment or were exposed to heat stress (HS). For 35 days, HS birds were fed a control diet and three levels of onion and ginger powder as: 5 g/kg ginger + 1.5 g/kg onion (T1), 10 g/kg ginger + 2.5 g/kg onion (T2), and 15 g/kg ginger + 3.5 g/kg onion (T3). Body weight, feed conversion ratio (FCR), dressing percentage, and the weight of immune-related organs improved in T2 compared to the control. Blood concentrations of malondialdehyde (MDA) and paraoxonase-1 (PON1) were substantially higher in T2 than the control. Similarly, in the same dietary group, the antibody titre against Newcastle disease (ND) and total leucocyte count (TLC) were greater than the control diet. The findings of this research indicate that 10 g of ginger combined with 2.5 g of onion in the diet enhance broiler growth performance, carcass quality, antioxidant status, and immunological response under heat stress conditions.

GYY4137, a H2S donor, ameliorates kidney injuries in diabetic mice by modifying renal ROS-associated enzymes

Diabetic nephropathy (DN) is a common microvascular complication of both type 1 and type 2 diabetes mellitus and often advances to end-stage renal disease. Oxidative stress plays an important role in the pathogenesis and progress of DN. Hydrogen sulfide (H2S) is considered as a promising candidate for the management of DN. But the antioxidant effects of H2S in DN have not been fully studied. In mouse model induced by high-fat diet and streptozotocin, GYY4137, a H2S donor, ameliorated albuminuria at weeks 6 & 8 and decreased serum creatinine at week 8, but not hyperglycemia. Renal nitrotyrosine and urinary 8-isoprostane were reduced along with the suppressed levels of renal laminin and kidney-injury-molecule 1. Renal NADPH oxidase (NOX) 2 was lower but heme oxygenase (HO) 2, paraoxonase (PON) 1, PON2 were higher in DN+GYY than DN group. NOX1, NOX4, HO1, superoxide dismutases 1–3 were similar between groups. Except for a rise at HO2, all the affected enzymes were unchanged in mRNA levels. The affected reactive-oxygen-species (ROS) enzymes were mainly located in the renal sodium-hydrogen-exchanger positive proximal tubules with similar distribution but changed immunofluorence in GYY4137 treated DN mice. Kidney morphological alterations in DN mice under light and electrical-microscopes were also improved by GYY4137. Thus, exogenous H2S administration may improve the renal oxidative damage in DN by reducing ROS production and enhancing ROS cleavage in kidney via the affected enzymes. This study may shed a light on therapeutic applications in diabetic nephropathy with H2S donors in the future.

Dumansız Tütün "Maraş Otu"nun Homosistein ve Kardiyovasküler Risk Parametreleri Üzerine Etkileri

Objective: This study aims to investigate the relationship between smokeless tobacco (Maras powder) and cigarette consumption with homocysteine, Paraoxonase-1 (PON-1), Arylesterase (ARE), and Lipoprotein-a (Lp (a)), which are known as risk factors for cardiovascular diseases.
 Material and Methods: The individuals included in the study were divided into three groups as Maras powder users (n = 38), cigarette smokers (n = 38), and healthy volunteers who did not use either tobacco group (n = 38). Serum homocysteine, PON-1, ARE, and Lp (a) levels of all participants were examined.
 Results: When the groups are compared, the highest homocysteine level was in the Maras powder group. While the difference between the control group and the Maras powder group was statistically significant, the difference between the control and smokers groups was statistically insignificant. Although PON values were lower in both the Maras powder and smokers groups than the control group, the difference was significant only in the smoking group. ARE was significantly lower, and Lp (a) was significantly higher in both tobacco smokers groups compared to the control group.
 Conclusion: Serum homocysteine, PON-1, ARE, and Lp (a) level are associated with Maras powder use. Homocysteine may be a useful early marker for cardiovascular disease in those who use Maras powder.

The association of paraoxonase 1 activities, serum mRNA expression and polymorphisms with in-stent coronary restenosis; a case-control study

BackgroundPON1 polymorphisms and enzyme activity have been reported to be associated with cardiovascular disease (CVD). The aim of current study was to assess the association of these PON1 SNPs and serum enzyme activity and with restenosis following coronary artery stenting. MethodsA total of 306 unrelated Iranian patients with history of coronary stent implantation who underwent elective re-angiography were enrolled in the current study. Three single nucleotide polymorphisms (SNPs) of PON1 gene were genotyped. We used a double ARMS PCR method for genotyping at the Q192R and L55M loci, and PCR-RFLP method for C-108 T. Serum mRNA expression of PON1 was determined using SYBER green method and Roche LightCycler. ResultsThere were 104 patients considered as in-stent restenosis (ISR) (mean age: 60.55 ± 8.60 years), and 202 individuals as non ISR (NISR) (mean age: 61.94 ± 9.18 years). There were no significant difference between paraoxonase and arylestrase actvities of paraoxonase 1 enzyme. Furthermore, there were no significant differences in the distribution of genotypes of PON1 polymorphism with ISR compared to the control group. The AAC haplotype was the most frequent haplotype in our population study, and haplotypes were not associated with ISR occurrence. The difference between serum mRNA expression of PON1 was not significant between ISR and NISR groups. ConclusionsAccording to our finding it seems that paraoxonase 1 activities, the most important polymorphisms of PON1 including Q192R, L55M and C-108 T and serum mRNA expression of PON1 are not beneficial markers for ISR diagnosis.

The role of oxidative stress parameters in the differential diagnosis of malignant and benign ascites.

Ascites is the pathological fluid accumulation in the peritoneal cavity and there are mainly two reasons for its etiology. These are malignant diseases such as hepatoma or pancreas cancer and benign diseases such as liver cirrhosis and heart failure. In this study, we investigated the diagnostic utility of arylesterase (ARES), paraoxonase (PON), stimulated paraoxonase (SPON), catalase (CAT) and myeloperoxidase (MPO) in the differential diagnosis of malignant and benign ascites. This study was conducted between February and September 2016. Patients with acute infection, those taking vitamin supplements and antioxidant medication, smoking, and drinking alcohol were excluded from the study. The study population consisted of 60 patients: 36 had benign (60%) and 24 had malignant (40%) ascites. The mean age of the patients was 63.3 years. MPO levels (14.2 vs. 4.2; p=0.028) were found to be higher and PON (2.6 vs. 4.5; p<0.001), SPON (10.7 vs. 23.9; p<0.001), ARES (615.7 vs. 823.5, p<0.001) and CAT (13.3 vs. 36.8; p=0.044) were found to be lower in malignant patients compared to benign patients. There was a positive correlation between PON, SPON, and ARES levels, and a negative correlation between MPO levels and SPON, ARES, and CAT levels. MPO levels showed superior diagnostic performance compared to ARES and CAT levels (p<0.05) for predicting malignancy but showed no diagnostic superiority compared to PON and SPON levels (p>0.05). PON, SPON, ARES, CAT, and MPO can be used with high sensitivity and specificity in the differential diagnosis of malignant and benign ascites.

Quantitative proteomics analysis of COVID-19 patients: Fetuin-A and tetranectin as potential modulators of innate immune responses

Treatment of severe cases of coronavirus disease 2019 (COVID-19) is extremely important to minimize death and end-organ damage. Here we performed a proteomic analysis of plasma samples from mild, moderate and severe COVID-19 patients. Analysis revealed differentially expressed proteins and different therapeutic potential targets related to innate immune responses such as fetuin-A, tetranectin (TN) and paraoxonase-1 (PON1). Furthermore, protein changes in plasma showed dysregulation of complement and coagulation cascades in COVID-19 patients compared to healthy controls. In conclusion, our proteomics data suggested fetuin-A and TN as potential targets that might be used for diagnosis as well as signatures for a better understanding of the pathogenesis of COVID-19 disease.

Paraoxonase-1, a novel link between periodontitis and ischemic heart disease: A case-control study.

Periodontitis is a chronic inflammatory disease and might be a potential risk factor for ischemic heart disease (IHD). However, the link between periodontitis and atherosclerosis is not yet fully understood. Paraoxonase-1 (PON-1) is a new biomarker representing both anti-atherosclerotic and antioxidant activity, which also acts against dental biofilm formation and periodontitis. The possible contributing role of PON-1 in the relationship between periodontitis and atherosclerosis has not been studied to date. The aim of the present study was to investigate the serum level of PON-1 with regard to the periodontal status in IHD patients. In this case-control study, 67 patients with IHD underwent a periodontal examination and were accordingly allocated to one of the 2 study groups: the case group with chronic periodontitis (n = 36); or the control group with a healthy periodontium (n = 31). Serum PON-1 activity was measured by means of colorimetric analysis. There were no significant differences between the groups in terms of demographic data, cardiac risk factors, initial biochemical test results, cardiac pump function, and the number of grafted vessels. The activity of PON-1 in cardiac patients suffering from periodontitis was significantly lower than in cardiac patients with a healthy periodontal status (53.01 ±7.53 U/mL and 59.11 ±9.95 U/mL, respectively; p = 0.007). This finding suggests that the combination of IHD and periodontitis is associated with lower PON-1 activity. Further studies might be required to assess the possible role of periodontal treatment in increasing PON-1 activity and reducing IHD severity.