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Graphical abstract, Highlights • The COVID-19 pandemic has challenged the healthcare capacity of many countries. • Strict, horizontal lockdowns have adverse social, economic and health effects that have not been fully considered. • Primary and community care have multiple roles in COVID-19 pandemic mitigation. • Greece is a case example of a country which neglected primary and community care, and in November 2020 implemented a second horizontal lockdown. • Primary and community care, represents the only realistic strategy for successful COVID-19 pandemic mitigation in the long-term., COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non−COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation.

As of 20 April, almost 1.7 million people globally have been diagnosed with Corona Virus Disease 2019 (COVID-19), a pandemic that has evolved from the emergence of a new coronavirus strain, acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in China. More than 170,000 deaths have been reported, while there are certainly many more cases of milder disease that have not been diagnosed and officially confirmed due to limited testing capacity in most countries. The pandemic is a global emergency due to the rapid transmission of the disease and the potential to overwhelm the healthcare systems, and is expected to have considerable economic and health impacts. Contributing factors and their possible role in the relatively high infection, death rates between countries and origin have recently been studied [1,2]. This new outbreak has been additionally evaluated for current knowledge on coronaviruses based on a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies [3]. The search for potential protective and therapeutic antiviral strategies is of particular and urgent concern [4]. While in most cases, especially in young people without any comorbidities, the disease is expected to be relatively mild, there is a substantial proportion of patients who develop complications and need intensive care-unit support and mechanical ventilation. In one case series of 1099 patients in China [5], 6.1 % of cases suffered from the primary composite end-point of admission to an intensive care unit, use of mechanical ventilation, or death. Patients with severe disease typically present with dyspnea and hypoxemia shortly after disease initiation, and may quickly progress to respiratory failure, acute respiratory distress syndrome (ARDS) and multi-organ failure [6]. Predictors of adverse outcomes include elevated levels of inflammatory markers and pro-inflammatory cytokines. A study of 150 COVID-19 cases reported that elevated levels of C-reactive protein (CRP), ferritin and IL-6 were associated with death [7]. IL-6, an important pro-inflammatory cytokine, was elevated in fatal cases of COVID-19 in another study of 191 patients [8]. Another study of 452 patients reported that those with severe disease showed lymphocytopenia, neutrophilia, low levels of monocytes, eosinophils and basophils, and elevated levels of infection-related biomarkers and inflammatory cytokines [9]. Pathological examination of a case in China revealed bilateral diffuse alveolar damage, desquamation of pneumocytes, hyaline membrane formation and interstitial mononuclear inflammatory infiltrates [10]. Flow cytometry of peripheral blood revealed reduced levels of CD4+ and CD8 + T cells, which however were hyper-activated, and elevated concentration of pro-inflammatory CCR6+ Th17 in CD4 + T cells. Such findings are hallmarks of ARDS and resemble features observed in SARS and Middle Eastern Respiratory Syndrome [11,12]. Systemic vasculitis was also observed [10]. Therefore, it seems that immune dysregulation may be implicated in the pathophysiology of severe COVID-19.

Micronutrients constitute an adjuvant treatment for respiratory viral infections. Since there is no effective antiviral therapy for COVID-19 yet, adjuvant intervention for the survival of critically ill patients may be significant. Search of the PubMed, CINAHL and Cochrane databases was carried out to find human studies investigating the prognostic role of micronutrient status and the effects of micronutrient supplementation intervention in COVID-19 outcomes of adult patients. Patients with certain comorbidities (diabetes mellitus type 2, obesity, renal failure, liver dysfunction etc.) or pregnant women were excluded. 31 studies (27 observational studies and 4 clinical trials) spanning the years 2020-2021, pertaining to 8624 COVID-19 patients (mean age±SD, 61 ± 9 years) were included in this systematic review. Few studies provided direct evidence on the association of serum levels of vitamin D, calcium, zinc, magnesium, phosphorus and selenium to patients' survival or death. Vitamin D and calcium were the most studied micronutrients and those with a probable promising favorable impact on patients. This review highlights the importance of a balanced nutritional status for a favorable outcome in COVID-19. Micronutrients' deficiency on admission to hospital seems to be related to a high risk for ICU admission, intubation and even death. Nevertheless, evidence for intervention remains unclear.

Over the last decades, the scientific findings stressing the beneficial health implications of plant-derived compounds (i.e., plant extracts rich in polyphenols) have been increased significantly. Assessing the properties of such compounds throughout the redox continuum is a common practice for the evaluation of their dynamics in reinforcing the antioxidant and antitoxic defence of tissues and, even, whole organisms or in the refinement of free radical-related disease onset. In the present contribution we propose a battery of translational biomarkers for measuring the antioxidant, antimutagenic and antitoxic capacities of plant compounds in three levels. The level 1 is the characterization of plant-derived compounds in vitro by detecting their antiradical and reducing capacity and their antimutagenic and anticarcinogenic properties. In the level 2, the tested agents should be administered in diverse cell lines in order to be examined for their antitoxic and antioxidant capacities. Although cell lines are considered as an in vitro system, it is undisputable that they are an in vivo-like environment and, thus, a link to in vivo settings. The level 3 is the administration of plant compounds in vivo, in experimental animals or humans either individually or as food supplements. The biomarkers for oxidative damage, antioxidant capacity and reducing/oxidative potential analyzed here seem to be suitable surrogate endpoints in the effort to extrapolate in vitro evidence to in vivo models. It is recommended that the aforementioned three lines of research (i.e., in vitro, cell culture environment and in vivo) should be applied in order to holistically reveal the biological action of plant polyphenolic compounds in the frame of redox biology and toxicology.

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs., Highlights • Anticoagulant therapy is essential in decreasing fibrin deposition and microthrombus formation in the ARDS and in the treatment of pro-thrombotic complications. • Administration of tPA in ARDS patients could provide anti-inflammatory effects. • Heparin and tPA may be useful in these patients minimizing the risk for ARDS complications and/or reducing the pressure on the ventilator support in the Intensive Care Unit

The aim of this study was to identify organic components eluted from five resin dental sealants using gas chromatography and mass spectrometry (GC/MS) after 1-day and 40-days storage and the effect of sealants on cell survival of cultured fibroblasts. Five resin materials were studied: BeautiSealant (SHOFU), Clinpro (3M/ESPE), Conseal F (SDI), Grandio Seal (VOCO) and Helioseal Clear (Ivoclar/Vivadent). The organic monomers detected were butylated hydroxytoluene (BHT), bis-phenol-A (BPA), camphoroquinone (CQ), diethylenglycoldimethacrylate (DEGDMA), 4N, N-dimethylaminobenzoic acid butylethoxyester (DMABEE), hydroxyethylmethcrylate (HEMA), hydroquinone monomethylether (MEHQ), triethylene glycol dimethacrylate (TEGDMA), tetrabutylammonium tetrafluoroborate (TBATFB), triphenylstibane (TPSb). The main monomer detected was TEGDMA, whereas BHT and DEGDMA were detected at lower concentrations. Higher monomer concentrations were detected after 40 days storage. The eluting chemical profiles of the tested materials differ qualitative and quantitative. For cytotoxicity evaluation, NIH/3T3 cells were exposed to eluates of sealants and cell viability was assessed by a quantitative technique at two observation periods. Decreased cell viability was observed. The cytotoxicity and the release of monomers from dental materials examined depends on the type of material and the observation time point. Resin-based dental materials have raised public concerns regarding possible adverse biological effects, thus it is essential to evaluate possible side effects for human health.

Cigarette smoke is a complex mixture of chemicals, including several tobacco-specific nitrosamines (TSNA). Most TSNA are formed in tobacco during the post-harvest period, while a number are produced when a cigarette is burned. Considerable evidence supports the role of TSNA important causative factors for cancers of the lung, pancreas, esophagus, and oral cavity in people who use tobacco products. Of the known TSNA, nicotine-derived nitrosamine ketone (NNK) and N-nitrosonornicotine (NNN) are the most carcinogenic. Other TSNA include N'-nitrosoanatabine (NAT) and N-nitrosoanabasine (NAB). New tobacco products (e.g., e-cigarettes) designed to attract consumers who are concerned about the health effects of tobacco have been appearing on the market. Several studies have reported that certain TSNA have been detected in the replacement liquids and vapour of e-cigarettes, but the levels are generally considerably lower than in tobacco cigarettes. Additionally, the FDA recently announced its intention to regulate TSNA in e-cigarettes, cigar tobacco and pipe tobacco. With the rise of new technologies for reducing the use of tobacco products-such as e-cigarettes- to evaluate exposure levels to these harmful chemicals over time, researchers will be monitoring levels of TSNA in the body as a result of the use of these devices.

Although the use of nutritional supplements by adult athletes has been extensively studied, information on supplements consumption by adolescent athletes is still limited. The present study reports on the use of nutritional supplements contaminated with banned doping substances among 170 recreational adolescent athletes from eleven, randomly selected, gym centres, in Athens, Greece. Nutritional supplements consumption was reported by almost 60% of the study population, with proteins/amino acids and vitamins being the most popular. Nine per cent of the users were found to consume nutritional supplements contaminated with anabolic steroids, prohormones, selective androgen receptor modulators (SARMs) and aromatase inhibitors, all pharmacological substances with endocrine modulating properties not stated on the label. None of these individuals had previously consulted a physician or a nutritionist. A representative sample (ca 15%) of the protein/aminoacids and creatine preparations used by the study population were also tested and found free from doping substances. The majority (63%) of adolescents purchased products from the internet. In conclusion, exercising adolescents can have easy access to contaminated nutritional supplements and "black market" products, which could constitute a risk for public health. Low level of awareness and low involvement of medical care professionals among recreational adolescent athletes is also observed.

Peppermint leaves are widely used for the symptomatic treatment of digestive disorders. Previous studies have shown significant effects of its natural products on human enzyme activity; however, there is no study available concerning the effects of peppermint tea on metabolizing enzymes in humans. Aim of the present study was to investigate the effect of peppermint tea on CYP1A2, CYP2A6, Xanthine Oxidase (XO), N-acetyltranferase-2 (NAT2) and UDP-glucuronosyltransferases-1A1/1A6 (UGT1A1/1A6) activities in healthy subjects. Four males and five females consumed peppermint tea (2 g of dry leaves/200 mL water, twice daily) for six days. CYP1A2, CYP2A6, XO, NAT2 and UGT1A1/1A6 activities were determined before and at the end of the study period, using the following caffeine and paracetamol metabolic ratios: CYP1A2: 17MX/137MX (saliva) and (AFMU+1MU+1MX)/17MU (urine); CYP2A6: 17MU/(17MU + 17MX), XO: 1MU/(1MU+1MX), NAT2, AFMU/(AFMU+1MU+1MX) and UGT1A1/1A6 glucuronidated/total paracetamol, all determined in urine. NAT2 metabolic ratio was significantly reduced following peppermint consumption (0.15 ± 0.13 vs 0.14 ± 0.13; p 0.05). CYP1A2 urine and saliva indices were reduced, yet not significantly, following peppermint consumption (urine: 3.17 ± 1.08 vs 2.91 ± 0.76, saliva: 0.56 ± 0.12 vs 0.50 ± 0.12; p 0.05). Peppermint had no influence on CYP2A6, XO and UGT1A1/1A6 indices. Daily ingestion of peppermint tea may alter pharmacokinetics of clinically administered drugs and promote cancer chemoprevention through NAT2 inhibition.

SARS-CoV-2 is the coronavirus that originated in Wuhan in December 2019 and has spread globally. Studies have shown that smokers are less likely to be diagnosed with or be hospitalized for COVID-19 but, once hospitalized, have higher odds for an adverse outcome. We have previously presented the potential interaction between SARS-CoV-2 Spike glycoprotein and nicotinic acetylcholine receptors (nAChRs), due to a “toxin-like” epitope on the Spike glycoprotein, with homology to a sequence of a snake venom toxin. This epitope coincides with the well-described cryptic epitope for the human anti-SARS-CoV antibody CR3022. In this study, we present the molecular complexes of both SARS-CoV and SARS-CoV-2 Spike glycoproteins, at their open or closed conformations, with the model of the human α7 nAChR. We found that all studied protein complexes' interface involves a large part of the “toxin-like” sequences of SARS-CoV and SARS-CoV-2 Spike glycoproteins and toxin binding site of human α7 nAChR. Our findings provide further support to the hypothesis about the protective role of nicotine and other cholinergic agonists. The potential therapeutic role of CR3022 and other similar monoclonal antibodies with increased affinity for SARS-CoV-2 Spike glycoprotein against the clinical effects originating from the dysregulated cholinergic pathway should be further explored., Highlights • The nicotinic cholinergic system may be involved in the pathophysiology of COVID19. • SARS-CoV and SARS-CoV-2 Spikes can interact with the human α7 nAChR. • SARS-CoV-2 through nAChRs may dysregulate the cholinergic anti-inflammatory pathway. • Interaction of SARS-CoV-2 Spike with nAChRs is due to a “toxin-like” sequence. • Cholinergic agonists' potential beneficial effects on COVID-19 should be explored.

The aim of the present study was to investigate the molecular mechanisms through which sheep/goat whey protein exerts its antioxidant activity. Thus, it was examined whey protein's effects on the expression of transcription factor, nuclear factor-like 2 (Nrf2) and on the expression and activity of a number of antioxidant and phase II enzymes, superoxide dismutase (SOD), catalase (CAT), heme oxygenase 1 (HO-1), synthase glutamyl cysteine (GCS) and glutathione-s-transferase (GST), in muscle C2C12 and EA.hy926 endothelial cells. C2C12 and EA.hy926 cells were treated with sheep/goat whey protein (0.78 and 3.12 mg/ml) and incubated for 3, 6, 12, 18 and 24 h. Whey protein increased significantly the expression of Nrf2 only in EA.hy926 cells. Also, the expression of SOD, HO-1, CAT and the activity of SOD, CAT and GST were increased significantly in both cells types. The expression of GCS was increased significantly only in C2C12 cells. Sheep/goat whey protein was shown for the first time to exert its antioxidant activity through Nrf2-dependent mechanism in endothelial cells and Nrf2-independent mechanism in muscle cells. Thus, Nrf2 could be a target for food supplements containing whey protein in order to prevent oxidative stress damages and diseases related to endothelium.

In the present study, a polyphenolic byproduct from olive mill wastewater (OMWW) was used for making piglet feed with antioxidant activity. For examining the antioxidant capacity of the feed, 30 piglets of 20 d old were divided into two groups receiving basal or experimental feed for 30 d. Blood and tissue samples were drawn at days 2, 20, 35 and 50 post-birth. The tissues collected were brain, heart, kidney, liver, lung, quadriceps muscle, pancreas, spleen and stomach. The antioxidant effects of the experimental feed were assessed by measuring oxidative stress biomarkers in blood and tissues. The oxidative stress markers were total antioxidant capacity (TAC), glutathione (GSH), catalase activity (CAT), protein carbonyls (CARB) and thiobarbituric acid reactive species (TBARS). The results showed that piglets fed with diet supplemented with OMWW polyphenols had significantly increased antioxidant mechanisms in blood and the majority of the tested tissues as shown by increases in TAC, CAT and GSH compared to control group. Moreover, piglets fed with the experimental feed exhibited decreased oxidative stress-induced damage to lipids and proteins as shown by decreases in TBARS and CARB respectively. This is the first study in which OMWW polyphenols were used for making pig feed with antioxidant activity.

We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P, Highlights • Tocilizumab improves endothelial glycocalyx and increases effective myocardial work. • IL-6 inhibition significantly reduces the inflammatory burden and oxidative stress. • Tocilizumab may have favorable effects on diseases with excess IL-6 release.

Obesity and thus, lipotoxicity, is a major health risk factor. Modern exposure to environmental chemicals has contributed significantly to the obesity epidemic. The purpose of this study was to assess, via telemedicine and using bioelectrical impedance analysis (BIA) in schools, the levels of adiposity and other body composition parameters of Greek adolescents in relation with their metabolic syndrome (MetS) characteristics. A representative sample (1575 adolescents, 14.4 ± 1.7 years-old) of the Attica region population, underwent body composition assessment of fat mass (FM), fat-free mass (FFM), and total body water (TBW) and was evaluated for anthropometric and MetS characteristics. Males demonstrated higher FFM% and TBW% but lower FM% than females. Adolescents with abdominal obesity/MetS (n = 149/n = 40) demonstrated significantly (P Findings suggest that early “osteosarcopenic” elements of abdominal obesity/MetS may exist even in adolescence. The application of BIA, incorporated in the new approach methodology of telemedicine in schools, identified adolescents at risk for obesity complications.

This study assessed the potential adverse health effects of long-term low-dose exposure to chemical mixtures simulating complex real-life human exposures. Four groups of Sprague Dawley rats were administered mixtures containing carbaryl, dimethoate, glyphosate, methomyl, methyl parathion, triadimefon, aspartame, sodium benzoate, calcium disodium ethylene diamine tetra-acetate, ethylparaben, butylparaben, bisphenol A, and acacia gum at doses of 0, 0.25, 1 or 5 times the respective Toxicological Reference Values (TRV): acceptable daily intake (ADI) or tolerable daily intake (TDI) in a 24 weeks toxicity study. Body weight gain, feed and water consumption were evaluated weekly. At 24 weeks blood was collected and biochemistry parameters and redox status markers were assessed. Adverse effects were observed on body weight gain and in hepatotoxic parameters such as the total bilirubin, alanine aminotransferase (ALT) and alkaline phosphatase (ALP), especially in low dose and affecting mainly male rats. The low dose group showed increased catalase activity both in females and males, whereas the high dose group exhibited decreased protein carbonyl and total antioxidant capacity (TAC) levels in both sex groups. Non-monotonic effects and adaptive responses on liver function tests and redox status, leading to non-linear dose-responses curves, are probably produced by modulation of different mechanisms.

Coffee is one of the most highly consumed beverages with potential beneficial health implications, however its molecular mechanism of action has not been completely elucidated yet. To that cause, the polyphenolic composition of different coffee extracts (from Light, Medium and Dark roasts as well as green beans) was examined by UHPLC-HRMS analysis, indicating chlorogenic acids isomers as the main constituents. In the following step, the toxicity of the extracts was tested in myoblasts and endothelial cells and differential toxicity of green and roasted samples was displayed as the myoblasts were more sensitive to green coffee extracts, in contrast to the endothelial cells. Subsequently, biologically relevant, non-cytotoxic extract concentrations were administered to explore their potential effect on cell redox status using flow cytometry and spectrophotometric assays. The results indicated that all coffee extracts improved cell redox status, however differences were observed between the two different cell lines tested, implying that coffee compounds display cell- and tissue-specificity. Glutathione levels were increased in almost all cases up to 70%, while the roasting degree affected the free radical scavenging potential of the extracts and their ability to protect from macromolecular oxidation as exhibited by the differences in ROS, CARB and TBARS levels, especially in the myoblasts.

The electronic cigarette (e-cig) is an invention of the past few years and its popularity is rapidly growing all over the world. A rapid multicomponent analytical protocol for the analysis of the replacement liquids (e-liquids) of e-cig was developed using gas (GC) and liquid chromatography (LC) – mass spectrometry (MS). GC – MS-based methods were developed for the determination of the main humectants and polycyclic aromatic hydrocarbons (PAHs). For the determination and quantification of nicotine (NIC) and nitrosamines, appropriate LC– MS-based methods were developed. The approbated methods were applied for the analysis of 263 e-liquid samples obtained from the Greek market. The instruments response was linear; the limits of quantification ranged from 0.003 mg/mL for three PAHs to 1.187 mg/mL for glycerol. The precision was

A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC₅₀ values of 121-230 μg/ml (MCF-7), 121-184 μg/ml (MDA-MD-23), 175-309 μg/ml (HT29), 159-314 μg/ml (K1), 180-225 μg/ml (786-0) and 134->400 μg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells.

The inhibitory potency of thirteen polyphenolic extracts obtained from vinification byproducts of Greek varieties of Vitis vinifera against glycogen phosphorylase (GP) has been studied by kinetic experiments. GP is an enzyme involved in glucose homeostasis and a molecular target for the discovery of new hypoglycemic agents. Studies have shown that all extracts display significant inhibitory potency for GP in vitro with IC50 values in the range of low μg/mL. X-ray crystallographic analysis of GP crystals soaked with two of these extracts revealed that the most active ingredient is quercetin which binds at novel binding site, distinct from the other known sites of the enzyme. One of the most potent of the studied extracts had also a moderate effect on glycogenolysis in the cellular lever with an IC50 value of 17.35 μg/mL. These results highlight the importance of natural resources in the quest for the discovery of new hypoglycemic agents, while at the same time they can serve as the starting point for their exploitation for antidiabetic usage and the development of novel biofunctional foods.

Elite athletes undergo heavy training programs throughout the year. The aim of the present study was to evaluate blood biomarkers of redox status, oxidative stress, inflammation and angiogenesis over the course of a competitive season in elite female water polo players. The biomarkers were evaluated in four distinct phases of an athletic season. It was found that the reduced glutathione (GSH) concentration was significantly increased, whereas catalase activity was decreased in erythrocytes in phases 3 and 4 compared to phase 2. Plasma concentration of thiobarbituric acid reactive substances (TBARS) was increased in phases 3 and 4 compared to phases 1 and 2, the concentration of protein carbonyls was increased in phase 4, and total antioxidant capacity (TAC) was decreased in phases 2 and 3. Plasma monocyte chemoattractant protein-1 (MCP-1) was decreased in phases 3 and 4; interleukin-10 (IL-10) was increased in phase 4, whereas no change was observed for adiponectin and endoglin. The findings of this study indicate that oxidative stress and inflammation varies over the season in elite female water polo athletes and this information might be used to apply remedies for optimizing athletic performance and accelerating training recovery.

The purpose of this study was to examine the effect of α-lipoic acid (LA) supplementation on blood redox status in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Eight adults with G6PD deficiency (D group) and eight controls with normal G6PD levels (N group) participated in this study. Participants received LA (600 mg/day) for 28 days. At baseline, 2 and 4 weeks after supplementation, venous blood was collected for analysis of reduced glutathione (GSH), catalase, protein carbonyls (PC), thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), bilirubin, uric acid (UA) and hemoglobin (Hb) levels. Baseline GSH was lower (P

Findings about involvement of reactive oxygen species (ROS) not only in defense processes, but also in a number of pathologies, stimulated discussion about their role in etiopathogenesis of various diseases. Yet questions regarding the role of ROS in tissue injury, whether ROS may serve as a common cause of different disorders or whether their uncontrolled production is just a manifestation of the processes involved, remain unexplained. Dogmatically, increased ROS formation is considered to be responsible for development of the so-called free-radical diseases. The present review discusses importance of ROS in various biological processes, including origin of life, evolution, genome plasticity, maintaining homeostasis and organism protection. This may be a reason why no significant benefit was found when exogenous antioxidants were used to treat free-radical diseases, even though their causality was primarily attributed to ROS. Here, we postulate that ROS unlikely play a causal role in tissue damage, but may readily be involved in signaling processes and as such in mediating tissue healing rather than injuring. This concept is thus in a contradiction to traditional understanding of ROS as deleterious agents. Nonetheless, under conditions of failing autoregulation, ROS may attack integral cellular components, cause cell death and deteriorate the evolving injury.

Intense exercise induces increased levels of pro-inflammatory and anti-inflammatory cytokines. Thus, the purpose of this study was to examine the effects of a special cake (consisting of carbohydrate to whey protein 3.5:1) vs. an isocaloric carbohydrate cake on inflammatory markers after exhaustive cycling in humans. Nine subjects received either the experimental or placebo cake in a counterbalanced fashion using a crossover, double-blind, repeated-measures design. They performed one trial involving a 2h exercise on a cycle ergometer at 60-65% VO2max followed by a 4h recovery and then a second trial involving an 1h exercise at 60-65% VO2max which was increased at 95% VO2max. Blood samples were collected pre-exercise, 30 min and 4h post-exercise, post-time Trial and 48 h post-time Trial. Cakes were consumed immediately post-exercise and every 1h for the next 3h. The results showed that consumption of the experimental cake reduced significantly (p

Among the various side effects of supra-physiological dose of anabolic androgenic steroids that are described, renal toxicity remains the least evaluated. The present study provides evidence that long-term administration of nandrolone decanoate could lead to alterations of renal function and structure in the experimental rabbit model. A pronounced increase in serum urea, creatinine, SGOT and SGPT is observed in the treated animals, with intramuscular administration being more detrimental. Histopathological evaluation of kidneys indicated hyperaemia, fibrosis and focal inflammation. Furthermore, the significantly increased telomerase activity found in the kidneys of the intramuscularly treated animals could possibly represent a counteracting survival mechanism. Oxidative stress markers that were influenced the most were TBARS, indicating lipid peroxidation, and GSH. An interesting finding in our study though, was that while intramuscular administration showed the highest biochemical derangement, oxidative stress markers provided mixed results between intramuscularly and subcutaneously treated rabbits. In conclusion, nephrotoxicity of nandrolone decanoate remains a multi-factorial, partly irreversible effect that involves augmented tissue oxidative status.

Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period.

In the present study, a ceramic membrane microfiltration method was used for the separation of two liquid products, the downstream permeate and the upstream retentate, from olive mill wastewater (OMWW). These liquid products were examined for their antioxidant activity by incorporating them into broilers' feed. Twenty four broilers 13 d old were divided into two feeding groups receiving supplementation with OMWW retentate or permeate for 37 d. Blood was drawn at 17, 27 and 37 d, while tissues (muscle, heart, liver) were collected at 37 d. The antioxidant effects were assessed by measuring oxidative stress biomarkers in blood and tissues. The results showed that broilers given feed supplemented with OMWW retentate or permeate had significantly lower protein oxidation and lipid peroxidation levels and higher total antioxidant capacity in plasma and tissues compared to control group. In both OMWW groups, catalase activity in erythrocytes and tissues was significantly increased compared to control group. OMWW retentate administration increased significantly GSH in erythrocytes in broilers with low GSH, although both OMWW products significantly reduced GSH in broilers with high GSH. Thus, it has been demonstrated for the first time that supplementation with OMWW processing residues could be used for enhancing broilers' redox status.

The aim of the present study was the assessment of the antioxidant effects of pomegranate juice (PJ) consumption in humans. Thus, 14 healthy volunteers consumed PJ daily for a period of 15 days and the changes of oxidative stress markers in their blood were assessed at four different time points, immediately before the experiment (T1), after 15 days of juice administration (T2), one (T3) and three weeks (T4) after the interruption of PJ administration. The markers studied were total antioxidant capacity (TAC), levels of malondialdehyde (MDA), and protein carbonyls (CARB) measured in plasma, as well as reduced glutathione (GSH), and catalase activity (CAT) measured in erythrocytes. The MDA was reduced by 24.4% at T3 and CARB were reduced by 19.6% and 17.7% at T2 and T3, respectively, supporting the evidence that PJ consumption enhances the antioxidant status in humans by decreasing lipid peroxidation and protein oxidation. Moreover, GSH levels were significantly increased (22.6%) at T2, indicating that PJ consumption improves the antioxidant mechanisms in erythrocytes by increasing GSH levels. Finally, it was shown that even a week after stopping PJ consumption some of its beneficial effects on antioxidant status still remained in the organism.

Extracellular matrices (ECMs) represent a complex network of proteins, proteoglycans and glycosaminoglycans (GAGs), composed of independent structural domains, ultimately constituting the cell microenvironment. As a highly organized, insoluble suprastructure, the ECM can, in a spatially patterned and regulated manner, integrate and deliver multiple complex signals to cells that affect their behavior. During the progression of carcinogenesis, tumor cells, through a continually changing interface, remodel and simultaneously interact with the components of ECM, as well as with surrounding stromal cells. Within this complex network of ECM components affecting tumor progression, reactive oxygen species/reactive nitrogen species (ROS/RNS) play a wide emerging role. In this minireview we will focus on the ROS-dependent modulations of tumor ECM and how this in turn affects the insidious pathways of tumor progression and dissemination.

Grape extracts and wine have been studied widely due to their beneficial effects on human health. However, there are only few studies from grape stems extracts. Therefore, the main objective of the present study was the assessment in stem extracts from Greek Vitis vinifera varieties of the total polyphenolic content (TPC), the identification of the polyphenols present in them, and the evaluation of their antioxidant activity, protection against ROS-induced DNA damage and inhibition of liver (HepG2) and cervical (HeLa) cancer cell growth. The range of the TPC in grape stem extracts was from 345 to 584 mg GAE/g dry weight. Moreover, stem extracts contained different classes of polyphenols as flavonols, flavanols, procyanidins, phenolic acids and stilbenes. In DPPH and ABTS assays, the IC50 values of the stem extracts had an average of 7.8 ± 2.8 and 5.4 ± 2.6 μg/mL respectively. Also, all stem extracts inhibited OH- and ROO-induced DNA damage dose dependent with average IC50 values of 478 ± 217 and 1.15 ± 0.85 μg/mL respectively. Furthermore, stem extracts inhibited at low concentrations the growth of HepG2 and HeLa cancer cells with average IC50 values of 50 ± 12 and 32 ± 16 μg/mL respectively. The above activities of grape stem extracts were comparable to those of seed extracts.

The World Health Organisation called for research assessing the safety of electronic cigarette (e-cigarette). We evaluated the acute effect of active and passive e-cigarette and tobacco cigarette smoking on complete blood count (CBC) markers in 15 smokers and 15 never-smokers, respectively. Smokers underwent a control session, an active tobacco cigarette smoking session, and an active e-cigarette smoking session. Never-smokers underwent a control session, a passive tobacco cigarette smoking session, and a passive e-cigarette smoking session.The results demonstrated that CBC indices remained unchanged during the control sessionand the active and passive e-cigarette smoking sessions (P > 0.05). Active and passive tobacco cigarette smoking increased white blood cell, lymphocyte, and granulocyte counts for at least one hour in smokers and never smokers (P < 0.05).It is concluded that acute active and passive smoking using the e-cigarettes tested in the current study does not influence CBC indices in smokers and never smokers, respectively. In contrast, acute active and passive tobacco cigarette smoking increase the secondary proteins of acute inflammatory load for at least one hour. More research is needed to evaluate chemical safety issues and other areas of consumer product safety of e-cigarettes, because the nicotine content in the liquids used may vary considerably.

Lamiaceae family species are considered important because of their use in folk medicine, culinary and flavouring throughout the world. Their interesting bioactivities are attributed mainly to essential oils, polyphenols and terpenes. However, there are only few studies about polyphenolic extracts from Lamiaceae plants. Thus, 24 polyphenolic extracts from three Lamiaceae genera, Salvia, Mentha and Sideritis, collected in Greece were examined for antioxidant and antibacterial activity in correlation with their polyphenolic content. The results showed that the tested polyphenolic extracts had strong free radical scavenging activity against DPPH· and ABTS(+) radicals and protected from hydroxyl and peroxyl radical-induced DNA damage. Moreover, five extracts inhibited Staphylococcus aureus growth. Furthermore, the results showed that the total polyphenolic content is not correlated with the above activities, although this relation was different within each plant genus. This is the first study regarding the antioxidant and antibacterial activity of Salvia pomifera ssp. calycina, S. pomifera ssp. pomifera, Mentha microphylla and Sideritis raeseri ssp. attica species, and one of the few concerning protection from DNA damage and antibacterial activity of polyphenolic extracts from the rest of the tested species.

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity.