Correlation of Systemic Inflammation Parameters and Serum SLFN11 in Small Cell Lung Cancer-A Prospective Pilot Study.

BACKGROUND AND OBJECTIVES: The objective of this research was to analyze the correlation of the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), soluble programmed cell death ligand 1 (sPD-L1), and Schlafen 11 (SLFN11) with the response to first-line chemotherapy in a cohort of small cell lung cancer (SCLC) patients, and to determine their potential as predictive serum biomarkers. MATERIALS AND METHODS: A total of 60 SCLC patients were included. Blood samples were taken to determine CRP, sPD-L1, and SLFN11 levels. The first sampling was performed before the start of chemotherapy, the second after two cycles, and the third after four cycles of chemotherapy. RESULTS: The patients who died earlier during the study had NLR and SLFN11 concentrations significantly higher compared to the survivor group. In the group of survivors, after two cycles of chemotherapy, the NLR ratio decreased significantly (p < 0.01), but after four cycles, the NLR ratio increased (p < 0.05). Their serum SLFN11 concentration increased significantly (p < 0.001) after two cycles of chemotherapy, but after four cycles, the level of SLFN11 fell significantly (p < 0.01). CRP, NLR, and SLFN11 were significant predictors of patient survival according to Kaplan-Meier analysis. The combination of inflammatory parameters and SLFN11 with a cutoff value above the 75th percentile of the predicted probability was associated with significantly lower overall survival in SCLC patients (average survival of 3.6 months vs. 4.8 months). CONCLUSION: The combination of inflammatory markers and the levels of two specific proteins (sPD-L1, SLFN11) could potentially serve as a non-invasive biomarker for predicting responses to DNA-damaging therapeutic agents in SCLC.

Childhood obesity accelerates biological ageing: is oxidative stress a link?

Obesity is multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed estimate connection between relative leukocyte telomere lengths (rLRL) - biomarker of cellular aging with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both genders. The results suggested that rLTL are significantly shorter in obese, compared to lean group (p<0,01). Negative correlation of rLTL with total oxidant status, TOS (Spearman's ρ = -0.365, p<0.001) as well as with C reactive protein (Spearman's ρ= -0,363, p<0.001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35% of total variability; antioxidant factor with 30% of total variability and lipid antioxidant - biological ageing factor with 12% of the total variability. The most important predictor of body mass index (BMI) >30kg/m2 according to logistic regression analysis was PCA derived antioxidant factor's score (OR: 1.66, 95th Cl: 1.05-2.6, p=0.029). PCA analysis confirmed oxidative stress importance in biological ageing caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homeostasis deepness, even before any overt disease occurrence.

Circulating Fatty Acids Associate with Metabolic Changes in Adolescents Living with Obesity.

Fatty acids play a crucial role in obesity development and in the comorbidities of obesity in both adults and children. This study aimed to assess the impact of circulating fatty acids on biomarkers of metabolic health of adolescents living with obesity. Parameters such as blood lipids, redox status, and leukocyte telomere length (rLTL) were measured alongside the proportions of individual fatty acids. The Mann-Whitney U test revealed that individuals with obesity exhibited an unfavorable lipid and redox status compared to the control normal weight group. The group with obesity also had lower plasma n-3 polyunsaturated fatty acids (PUFAs) and a higher ratio of n-6 to n-3 PUFAs than the control group. They also had a shorter rLTL, indicating accelerated biological aging. There was an inverse association of rLTL and plasma n-6-to-n-3 PUFA ratio. Future studies should explore the impact of recommended nutrition plans and increased physical activity on these parameters to determine if these interventions can enhance the health and well-being of adolescents with obesity, knowing that early obesity can track into adulthood.

Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach.

Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dismutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting "no-threshold" concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies.

Increased oxidative stress in shoe industry workers with low-level exposure to a mixture of volatile organic compounds.

This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O2 •-), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.

The influence of Klotho protein and prooxidant-antioxidant balance combination on the mortality of HD patients.

PURPOSE: End-stage renal disease patients on chronic hemodialysis (HD) have a shortened life expectancy compared to the general population. The aim of this study was to evaluate a possible link between three new and emerging factors in renal pathophysiology: Klotho protein, telomere length in peripheral blood mononuclear cells (TL) and redox status parameters before HD (bHD) and after HD (aHD), and to test mortality prediction capability of these emerging parameters in a population of HD patients. METHODS: The study included 130 adult patients with average age 66 (54-72), on HD (3 times per week; 4-5 h per session). Klotho level, TL, routine laboratory parameters, dialysis adequacy and redox status parameters: advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), superoxide anion (O2.-), malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl group content (SHG), and superoxide dismutase (SOD) were determined. RESULTS: Klotho concentration was significantly higher aHD; 68.2 (22.6-152.9) vs. bHD 64.2 (25.5-119.8) (p = 0.027). The observed increase in TL was not statistically significant. AOPP, PAB, SHG, and SOD activity were significantly increased aHD (p > 0.001). The patients with the highest mortality risk score (MRS) had significantly higher PAB bHD (p = 0.002). Significantly lower O2.- (p < 0.001), SHG content (p = 0.072), and IMA (p = 0.002) aHD were found in patients with the lowest MRS values. Principal component analysis revealed redox balance-Klotho factor as a significant predictor of high mortality risk (p = 0.014). CONCLUSION: Decreased Klotho and TL attrition as well as redox status disturbance could be connected with higher mortality rate in HD patients.

Correlation of Short Leukocyte Telomeres and Oxidative Stress with the Presence and Severity of Lung Cancer Explored by Principal Component Analysis.

Lung cancer (LC) is the second most common malignancy and leading cause of cancer death. The potential "culprit" for local and systemic telomere shortening in LC patients is oxidative stress. We investigated the correlation between the peripheral blood leukocyte (PBL) telomere length (TL) and the presence/severity of LC and oxidative stress, and its usefulness as LC diagnostic marker. PBL TL was measured in 89 LC patients and 83 healthy subjects using the modified Cawthon RTq-PCR method. The relative PBL TL, found to be a potential diagnostic marker for LC with very good accuracy (P < 0.001), was significantly shorter in patients compared to the control group (CG) (P < 0.001). Significantly shorter telomeres were found in patients with LC TNM stage IV than in patients with stages I-III (P = 0.014), in patients without therapy compared to those on therapy (P = 0.008), and in patients with partial response and stable/progressive disease compared to those with complete response (P = 0.039). The total oxidant status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB) and C-reactive protein (CRP) were significantly higher in patients compared to CG (P < 0.001) and correlated negatively with TL in both patients and CG (P < 0.001). PCA showed a relation between PAB and TL, and between the EGFR status and TL. Oxidative stress and PBL telomere shortening are probably associated with LC development and progression.

Analysis of redox status and HDL subclasses in patients with lymphoma and the associations with FDG-PET/CT findings.

Newer research points to alterations in the plasma redox status and the HDL subclass distributions in cancer. We aimed to assess the redox status and the HDL subclass distributions, lipids, and inflammatory markers in lymphoma patients in order to determine whether they were correlated with changes in FDG-PET/CT scans. At the beginning of this study, redox status, HDL subclasses, lipids, and inflammation biomarkers were determined in 58 patients with lymphoma (Hodgkin lymphoma, n=11 and non-Hodgkin lymphoma, n=47), and these same measurements were reassessed during their ensuing treatment (in 25 patients). Initially, the total oxidation status (TOS), the prooxidant-antioxidant balance (PAB), the OS index (OSI), the total protein sulfhydryl groups (SH-groups), and the advanced oxidation protein products (AOPP) were significantly higher in lymphoma patients as compared to healthy subjects, but the total antioxidant status (TAS) was significantly reduced. The PAB had a strong correlation with the CRP and interleukin-6 (rho=0.726, p<0.001; rho=0.386, p=0.003). The correlations between these parameters and the maximum standardized uptake values (SUVmax) were: PAB, rho=0.335 and p=0.010; SH-groups, rho=0.265 and p=0.044; CRP, rho=0.391 and p=0.002; HDL3b, rho=0.283 and p=0.031; HDL2b, rho= -0.294 and p=0.025; and HDL size, rho= -0.295 and p=0.024. The reductions in SUVmax between two follow-up points were associated with increases in the OSI, TOS, and SH-groups, as well as a reduction in the PAB and TAS. In conclusion, the redox parameters in patients with lymphoma were consistent with FDG-PET/CT findings. Targeting the redox status parameters and the HDL subclasses could be potential strategies in the molecular fight against lymphoma.

Principal component analysis of the oxidative stress, inflammation, and dyslipidemia influence in patients with different levels of glucoregulation.

Background: The aim of the study was to explore the mutual relationship between oxidative stress, inflammation and metabolic biomarkers in subjects with prediabetes (PRE), newly diagnosed type 2 diabetes patients (NT2D) and overt type 2 diabetes (T2D) using principal component analysis (PCA) as a thorough statistical approach. Methods: Glycated hemoglobin, lipid parameters, inflammation (IL-6, CRP and fibrinogen) and oxidative stress markers pro-oxidants (AOPP, PAB, TOS) and antioxidants (PON1, tSHG, TAS) were measured. PCA was applied to explore the factors that the most strongly influenced glucoregulation. Results: A total of 278 subjects were (i.e., 37 PRE, 42 NT2D and 99 T2D) were compared with 100 healthy subjects as a control group (CG). PCA emphasized 4 different factors explaining 49% of the variance of the tested parameters: oxidative stress-dyslipidemia related factor (with positive loading of TG and tSHG, and with negative loading of HDL-c and TAS), dyslipidaemia related factor (i.e., total cholesterol and LDL-c, both with positive loading), Anthropometric related factor (i.e., waist and hip circumference, both with positive loading) and oxidative stressInflammation related factor (i.e., PAB, fibrinogen, and CRP all with positive loading). Out of these 4 factors, only oxidative stress - dyslipidaemia related factor showed a significant predictive capability towards poor glucoregulation. An increase in this factor by one unit showed a 1.6 times higher probability for poor glucoregulation. Conclusions: Redox imbalance (determined with lower TAS and higher tSHG), in addition to higher TG and lower HDLc was associated with poor glucoregulation.

Ex vivo and in vivo antioxidant activity of ß-hydroxy-ß-arylalkanoic acids.

The interplay between oxidative stress and inflammation is implicated in many chronic diseases including Alzheimer`s disease, cardiovascular diseases, diabetes and cancer. Thirteen ß-hydroxy-ß-arylalkanoic acids were previously synthesized and evaluated for their anti-inflammatory activity. The aim of this study was to asses ex vivo antioxidant activity of synthesized acids, as well as ibuprofen and to identify the compounds with the most promising results for further investigation on their capacity to counteract in vivo oxidative stress triggered by inflammation. The antioxidant potential of tested compounds was evaluated by determining the concentrations of total antioxidative status, total oxidative status, prooxidant antioxidant balance and the total sulfhydryl groups. Z score statistics were used to calculate the summary scores for antioxidative activity, prooxidative activity and oxy score. The tested compounds and ibuprofen demonstrated mild prooxidative activity ex vivo. Seven acids with substituents on one benzene ring exhibited better results than ibuprofen and were selected for in vivo testing. In vivo results demonstrated better antioxidant protection compared to ex vivo results. Compound g which contains nitro group on the benzene ring demonstrated the lowest oxy score, and four compounds exhibited better results than ibuprofen.

Analysis of the Prognostic Potential of Schlafen 11, Programmed Death Ligand 1, and Redox Status in Colorectal Cancer Patients.

The Schlafen 11 (SLFN11) protein has recently emerged as pivotal in DNA damage conditions, with predictive potential for tumor response to cytotoxic chemotherapies. Recent discoveries also showed that the programmed death ligand 1 (PD-L1) protein can be found on malignant cells, providing an immune evasion mechanism exploited by different tumors. Additionally, excessive generation of free radicals, redox imbalance, and consequential DNA damage can affect intestinal cell homeostasis and lead to neoplastic transformation. Therefore, our study aimed to investigate the significance of SLFN11 and PD-L1 proteins and redox status parameters as prognostic biomarkers in CRC patients. This study included a total of 155 CRC patients. SLFN11 and PD-L1 serum levels were measured with ELISA and evaluated based on redox status parameters, sociodemographic and clinical characteristics, and survival. The following redox status parameters were investigated: spectrophotometrically measured superoxide dismutase (SOD), sulfhydryl (SH) groups, advanced oxidation protein products (AOPP), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), and superoxide anion (O2•-). The prooxidative score, antioxidative score, and OXY-SCORE were also calculated. The results showed significantly shorter survival in patients with higher OXY-SCOREs and higher levels of serum SLFN11, while only histopathology-analysis-related factors showed significant prognostic value. OXY-SCORE and SLFN11 levels may harbor prognostic potential in CRC patients.

Serum Endocan Levels in Postmenopausal Women with Metabolic Syndrome.

Aim: Studies that explored endocan (as a novel marker of endothelial dysfunction) in relation to metabolic syndrome (MetS) are scarce and show discordant results. Importantly, no study has yet examined serum endocan levels in exclusively postmenopausal women with MetS and free of diabetes. Oxidative stress and inflammation are the key features of MetS and consequently cardiovascular diseases. Hence, we aimed to explore the potential relationship between endocan, oxidative stress [i.e., determined by total antioxidant status, total oxidant status, and pro-oxidant/antioxidant balance (PAB)], inflammation, and MetS in a cohort of postmenopausal women. Methods: A total of 126 postmenopausal women were included consecutively. MetS was diagnosed following the International Diabetes Federation criteria. Results: Higher serum endocan levels were found in MetS group as compared with MetS-free counterparts [6.03 (3.47-10.37) pg/mL vs. 2.27 (1.49-3.50) pg/mL, P < 0.001]. Endocan showed good discriminatory ability toward MetS [area under the curve (AUC) = 0.809]. Besides age, the inclusion of oxidative stress and inflammation biomarkers, such as PAB and high-sensitivity C-reactive protein (hsCRP), the AUC for discrimination postmenopausal women with MetS from MetS-free women was 0.845. Conclusion: Postmenopausal women with MetS exhibited almost 2.7 times higher serum endocan level as compared with MetS-free middle-aged women. Endocan showed good discriminatory ability toward MetS and could be a diagnostic marker in MetS. Similar results were confirmed when added an age, oxidative stress, and inflammation biomarkers (i.e., PAB and hsCRP) were included for the discrimination of postmenopausal with MetS from MetS-free women.

The antidepressant drugs vortioxetine and duloxetine differentially and sex-dependently affect animal well-being, cognitive performance, cardiac redox status and histology in a model of osteoarthritis.

Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive disorders, which can be exacerbated by osteoarthritis or drugs used for its treatment. Here, we examined the behavioral and cardiac effects of the novel antidepressant vortioxetine in an osteoarthritis model, and compared them to duloxetine (an established osteoarthritis treatment). Osteoarthritis was induced in male and female rats with an intraarticular sodium-monoiodoacetate injection. Antidepressants were orally administered for 28 days following induction. During this period the acetone, burrowing and novel-object-recognition tests (NORT) were used to assess the effects of antidepressants on pain hypersensitivity (cold allodynia), animal well-being and cognitive performance, respectively. Following behavioral experiments, heart muscles were collected for assessment of redox status/histology. Antidepressant treatment dose-dependently reduced cold allodynia in rats with osteoarthritis. Duloxetine (but not vortioxetine) depressed burrowing behavior in osteoarthritic rats in a dose-related manner. Osteoarthritis induction reduced cognitive performance in NORT, which was dose-dependently alleviated by vortioxetine (duloxetine improved performance only in female rats). Furthermore, duloxetine (but not vortioxetine) increased oxidative stress parameters in the heart muscles of female (but not male) rats and induced histological changes in cardiomyocytes indicative of oxidative damage. Vortioxetine displayed comparable efficacy to duloxetine in reducing pain hypersensitivity. Furthermore, vortioxetine (unlike duloxetine) dose-dependently improved cognitive performance and had no adverse effect on burrowing behavior (animal surrogate of well-being) and cardiac redox status/histology. Our results indicate that vortioxetine could be a potential osteoarthritis treatment (with better characteristics compared to duloxetine).

Redox Status and Telomere-Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2•-), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere-telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The "cholesterol-protein factor" and "oxidative-telomere factor" were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the "oxidative-telomere factor" (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length.

Magnesium suppresses in vivo oxidative stress and ex vivo DNA damage induced by protracted ACTH treatment in rats.

Oxidative stress, arising from disrupted balance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant defences, has been implicated in the pathogenesis of stress-related disorders. There is a growing body of evidence that supports the relationship between the activity of the hypothalamic-pituitary-adrenal (HPA) stress system, oxidative stress and magnesium (Mg) homeostasis. The present study aimed to explore the gap in our current understanding of antigenotoxic and protective effects of Mg supplementation against excessive ROS production in male rats during chronic treatment with adrenocorticotropic hormone (ACTH). Our findings show that exposure to exogenous ACTH (10 µg/day, s.c., for 21 days), as one of the key mediators of the HPA axis and stress response, produced an increase in superoxide anion levels and a decrease in superoxide dismutase activity in plasma. We observed that Mg supplementation, starting seven days prior to ACTH treatment and lasting 28 days (300 mg/L of drinking water, per os), abolished these effects in experimental animals. Moreover, our study reveals that ACTH increased the susceptibility of peripheral blood lymphocytes to ex vivo H2O2-induced total and high-level oxidative DNA damage, while Mg completely reversed these effects. Collectively, these results highlight the promising role of Mg in stress-related conditions accompanied by increased oxidative stress in animals and support further investigation using human dietary trials.

HDL Subclasses and the Distribution of Paraoxonase-1 Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction.

The aim of this multicentric study was to assess the impacts of oxidative stress, inflammation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins' subclasses were separated using polyacrylamide gradient (3-31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL.

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.

Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application.

Introduction: Phenols are a large family of natural and synthetic compounds with known antioxidant activity. The aim of this study was to perform in vitro screening of natural and natural-like phenol monomers and their C2-symmetric dimers (hydroxylated biphenyls) in order to identify those representatives whose pharmacophores have the strongest antioxidant and the lowest prooxidant activity. Material and methods: Antioxidative properties of 36 compounds (monomers and their C2-symmetric dimers) were evaluated in vitro. Different (red/ox) assays were used to measure their total oxidative potential (TOP), their total antioxidative capacity (TAC), the pro-oxidative-antioxidant balance (PAB) and total SH-group content (SHG) in a biologically relevant environment. The Pro-oxidative Score, Antioxidative Score and the Oxy Score were also calculated. Trolox, a water soluble analogue of α-tocopherol, was used as a positive control. Results: In an assay consisting of pooled human serum, 6 of the 36 compounds showed significant antioxidant activity (compounds 6, 7, 12, 13, 26, and 27), whereas 4 showed extremely weak antioxidant activity (compounds 2, 29, 30, and 31). Within the 36 compounds comprising zingerone, dehydrozingerone, aurone, chalcone, and magnolol derivatives, in both monomeric and dimeric forms, the 2 compounds that indicated the highest antioxidant activity were dehydrozingerone derivatives (compounds 6 and 12). Trolox's activity was found between the strong and weak antioxidant compounds analysed in our study. Conclusions: In this study selected dehydrozingerones were identified as good candidates for in-depth testing of their biological behaviour and for possible precursors for synthesis of novel polyphenolic molecules with potential therapeutic applications.

Endocan is Related to Increased Cardiovascular Risk in Type 2 Diabetes Mellitus Patients.

Aim: Type 2 diabetes mellitus (T2D) patients have an increased risk for cardiovascular disease (CVD). Different algorithms are used for the CVD risk quantification and United Kingdom Prospective Diabetes Study (UKPDS) score was among the most validated. Endocan is a novel endothelial dysfunction marker. The aim was to explore the potential relationship between serum endocan level and UKPDS risk engine score [which enables calculation of the 10-year risk of nonfatal and fatal coronary heart disease (eCHD) and stroke] in T2D patients. Materials and Methods: The study included a cohort of 104 patients with T2D (of them 52.8% men), with median age 66 years and body mass index (BMI) = 30.7 kg/m2. Patients were divided into: low (<15%), moderate (≥15% and <30%), and high-risk UKPDS category (≥30%). Results: In multivariable regression analysis (when adjusted for sex, BMI and/or hip circumference), endocan was the independent predictor for moderate and high estimated risks (nonfatal eCHD, fatal eCHD, and nonfatal stroke risk). In the Model for high nonfatal eCHD [areas under curve (AUC) = 0.895] and high fatal eCHD (AUC = 0.860) endocan indicated good clinical accuracy, and an excellent accuracy in discriminating patients with high risk for nonfatal stroke risk (AUC = 0.945). Conclusion: Endocan was the independent predictor for moderate and high estimated risks (i.e., nonfatal and fatal CHD and nonfatal stroke risk scores) in T2D patients. When included in models with sex and obesity indices endocan demonstrated good clinical accuracy in discriminating T2D patients with high risk for nonfatal and fatal eCHD and nonfatal stroke risk from those patients with low risk.

The Prospect of Genomic, Transcriptomic, Epigenetic and Metabolomic Biomarkers for The Personalized Prevention of Type 2 Diabetes and Cardiovascular Diseases.

Cardiometabolic diseases, such as type 2 diabetes mellitus (DM) and cardiovascular disease (CVD), are a great health concern. The strategies aimed to increase awareness and prevention, in conjunction with timely diagnosis and optimal management of these conditions, represent the main lines of action to improve life expectancy and quality. In recent years, the introduction of innovative therapies for the treatment of DM and CVD has provided new hope for high-risk patients. Yet, the implementation of preventive measures in achieving cardiometabolic health is far from successful and requires further improvement. The development of cardiometabolic disorders is a complex, multifactorial process involving several metabolic pathways as well as genetic and environmental factors. Decreasing cumulative exposure during the entire life course and timely recognition and targeting of potential riskenhancing factors could pave the way toward more successful prevention of cardiometabolic disorders. Nowadays, in the era of "omics" technologies, it is possible to identify novel biomarkers and therapeutic targets, which offers the possibility to apply an individualized approach for each patient. This review will discuss potential applications of genomic, transcriptomic, epigenetic and metabolomic biomarkers for the personalized prevention of cardiometabolic diseases.