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Long-distance running has become increasingly popular. Cardiovascular adaptations to exercise are relevant to the specific sports and this is also the case in long-distance running. Significant changes regarding inflammatory and endothelial markers along with indices of oxidative stress are observed in marathon and ultra-marathon runners. However, data linking inflammatory marker levels with cardiovascular adaptations to marathon running are limited. The aim of the present study was to describe the cardiovascular adaptations observed in a group of ultra-marathon runners and the association with a series of inflammatory and endothelial markers measured in their plasma. A total of 43 ultra-marathon runners were assessed by echocardiography and a treadmill exercise test. Blood samples were used for tumor necrosis factor-α (TNF-α), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, IL-10, C-reactive protein, creatine phosphokinase (CPK) and oxidative stress indice measurements. Ultra-marathon runners who presented augmented left ventricular (LV) end diastolic diameters55 mm had higher ADMA values (1.07±0.07 vs. 0.99±0.08 µmol/ml, P0.01) and lower CPK values (192.5±21.3 vs. 219.1±37.3 mg/dl, P0.05) compared with those with normal LV diameters. Runners with a moderate and severe abnormal indexed LV mass131 g/m

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.

Anthracyclines are commonly used anticancer drugs with well‑known and extensively studied cardiotoxic effects in humans. In the clinical setting guidelines for assessing cardiotoxicity are well‑established with important therapeutic implications. Cardiotoxicity in terms of impairment of cardiac function is largely diagnosed by echocardiography and based on objective metrics of cardiac function. Until this day, cardiotoxicity is not an endpoint in the current general toxicology and safety pharmacology preclinical studies, although other classes of drugs apart from anthracyclines, along with everyday chemicals have been shown to manifest cardiotoxic properties. Also, in the relevant literature there are not well‑established objective criteria or reference values in order to uniformly characterize cardiotoxic adverse effects in animal models. This in depth review focuses on the evaluation of two important echocardiographic indices, namely ejection fraction and fractional shortening, in the literature concerning anthracycline administration to rats as the reference laboratory animal model. The analysis of the gathered data gives promising results and solid prospects for both, defining anthracycline cardiotoxicity objective values and delineating the guidelines for assessing cardiotoxicity as a separate hazard class in animal preclinical studies for regulatory purposes.

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, human activities prompted the high production and widespread use of household chemical products, leading to daily exposure of humans to several chemicals. The objective of this study was to investigate the frequency of chemicals’ use by children and parents in Greece and estimate the level of risk awareness and understanding among them. A total of 575 parents and children were asked to answer an anonymous, closed-ended, validated, and self-administered questionnaire. One-third of the children and almost half of the parents participating in the study believed that commonly used chemical products do not pose any risk to human health or to the environment, despite the product labelling. The majority of both children (61.8%) and parents (70.6%) were informed about product safety via the product labelling. Around 20% in both groups could not differentiate between systemic toxicity and acute lethal effects depicted by pictograms on the label and milder hazards, such as skin irritation. Moreover, the information on hazard and precautionary statements appearing on the label was very poorly perceived. Therefore, as both children and parents seem not to clearly identify the hazards and risks arising from the use of everyday chemical products, targeted awareness policies should be implemented to support the safe use of household products.

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.

Sixty inflammatory bowel disease (IBD) patients (45 Crohn disease and 15 ulcerative colitis, 40 ± 13 years, 53% male) were examined at baseline and 4 months after intervention (surgical (35 patients) or anti-TNFa treatment (25 patients)). IBD severity, using Mayo score, Harvey–Bradshaw Index (HBI) and biomarkers, was correlated with cardiovascular markers. At baseline, the disease severity, the white blood cells (WBC) values and the reducing power (RP) were significantly correlated with the aortic pulse wave velocity (PWV) (r = 0.4, r = 0.44 and r = 0.48, p < 0.05) and the lateral mitral E’ velocity (r = 0.35, p < 0.05 and r = 0.3, p < 0.05). Four months after intervention, there was a reduction of WBC (1962.8/mm3 ± 0.425/mm3, p < 0.001), C-reactive protein (CRP) (8.1 mg/L ± 1.7 mg/L, p < 0.001), malondialdehyde (MDA) (0.81 nmol/mg ± 0.37, p < 0.05) and glycocalyx perfused boundary region (PBR 5-25) (0.24 μm ± 0.05 μm, p < 0.01). Moreover, the brachial flow mediated dilatation (FMD), the coronary flow reserve (CFR) and the left ventricle global longitudinal strain (LV GLS) were significantly improved for both groups (4.5% ± 0.9%, 0.55 ± 0.08, 1.4% ± 0.35%, p < 0.01), while a more significant improvement of PWV/GLS was noticed in the anti-TNFa group. IBD severity is associated with vascular endothelial, cardiac diastolic, and coronary microcirculatory dysfunction. The systemic inflammatory inhibition and the local surgical intervention lead to significant improvement in endothelial function, coronary microcirculation and myocardial deformation.

The present Special Issue of Antioxidants, entitled The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile In Vitro and In Vivo, ten research articles emphasize the significance of adopting reliable redox biomarkers to determine the antioxidant activities of bioactive compounds in vitro and to assess blood and tissue redox status in vivo [...]

One of the most studied question in modern history is the particular way of bridging the gap between lifespan and healthspan? Even as average life expectancy has increased, there remains a sizeable gap between life span and health span — the years an individual lives without disease. The second question we must answer is the possibility that our lifespan and/or healthspan is “Programmed” in our genes? Or maybe there are other parameters that contribute to this model? Genome Analysis with “single nucleotide polymorphisms” (SNPs) of exceptionally long-lived people reveal 10-15% complex genetic signatures and very few genes consistently involved. The rest refers to the 3 pillars of metabolic health, the diet, the exercise, and the use of fasting in our everyday plan. Nutrient influence on healthy aging is being extensively studied in humans and in many animal models of aging. Moreover, the latest evidence is showing that regular physical activity can actually slow the aging process on a cellular level and potentially add years to your life. Additionally, intermittent fasting elicits evolutionarily conserved, adaptive cellular responses that are integrated between and within organs in a manner that improves glucose regulation, increases stress resistance, and suppresses inflammation. All these measurements proposed by our research team provides a holistic approach for the evaluation of redox status parameters for several conditions. Therefore, the effect of personalized nutrition on human redox status is evaluated and human health is improved.

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

Subsequently to the publication of this paper, the authors have realized that the name of the seventh listed author, Dimitrios Stagos, was spelt incorrectly (it appeared as 'Stagkos' in print). The corrected author list is shown above. The authors regret that the name of the seventh author on the paper was spelt incorrectly, and apologize to the readers for any inconvenience caused.[the original article was published in Oncology Reports 44: 798-818, 2020; DOI: 10.3892/or.2020.7688].

Background Diabetes is regarded as an epidemiological threat for the twenty-first century. Phytochemicals with known pharmaceutical properties have gained interest in the field of alleviating secondary complications of diseases. Such a substance is crocin, a basic constituent of saffron (Crocus sativus). The present study aimed at examining the beneficial effects of per os crocin administration on the antioxidant status, blood biochemical profile, hepatic gene expression and plasminogen activator inhibitor-1 activity (PAI-1) in the liver, kidney and plasma (an important marker of pre-diabetic status and major factor of thrombosis in diabetes) of healthy rats, as well as of rats with nicotinamide-streptozotocin-induced diabetes. Results Diabetes disrupted the oxidation-antioxidation balance, while crocin improved the antioxidant state in the liver by significantly affecting SOD1 gene expression and/or by restoring SOD and total antioxidant capacity (TAC) levels. In the kidney, crocin improved hydrogen peroxide decomposing activity and TAC. In blood, hepatic transaminases ALT and AST decreased significantly, while there was a trend of decrease regarding blood urea nitrogen (BUN) levels. The expression of PAI-1 gene was affected in the liver by the dose of 50 mg kg−1. Conclusions Crocin treatment contributed in restoring some parameters after diabetes induction, primarily by affecting significantly hepatic transaminases ALT and AST, SOD1 and PAI-1 gene expression and nephric H2O2 decomposing activity. In conclusion, crocin did contribute to the alleviation of some complications of diabetes.

Heat stress is a known promoter of reactive oxygen species generation, which may compromise pregnancy and foetal development. Melatonin is a pleiotropic molecule that regulates various processes including pregnancy. Thus, it could be used to ameliorate the redox status of pregnant heat-stressed ewes and the outcome of their pregnancy. Sixty-eight ewes participated in the study, which were allocated into two equal groups, i.e., Melatonin (M) and Control (C) group. All ewes were exposed to heat stress from D0 to D120. In both groups, after oestrus synchronization of ewes, rams were introduced to them for mating (D16). In M group, starting with sponges&rsquo, insertion (D0), melatonin implants were administered four-fold every 40 days. Pregnancy diagnosis was performed by means of ultrasonography. Daily evaluation of temperature humidity index (THI), rectal temperature, and breathing rate were performed throughout the study. Blood samples were collected repeatedly from D0 until weaning for assaying redox biomarkers. Milk yield was measured thrice during puerperium. The results showed that melatonin administration throughout pregnancy improved the redox status of heat-stressed ewes and increased the mean number and bodyweight of lambs born per ewe, as well as the milk production. Therefore, melatonin may be used as antioxidant regimen in heat-stressed ewes for improving their reproductive traits.

In this research, a model for the estimation of antioxidant content in cherry fruits from multispectral imagery acquired from drones was developed, based on machine learning methods. For two consecutive cultivation years, the trees were sampled on different dates and then analysed for their fruits&rsquo, radical scavenging activity (DPPH) and Folin&ndash, Ciocalteu (FCR) reducing capacity. Multispectral images from unmanned aerial vehicles were acquired on the same dates with fruit sampling. Soil samples were collected throughout the study fields at the end of the season. Topographic, hydrographic and weather data also were included in modelling. First-year data were used for model-fitting, whereas second-year data for testing. Spatial autocorrelation tests indicated unbiased sampling and, moreover, allowed restriction of modelling input parameters to a smaller group. The optimum model employs 24 input variables resulting in a 6.74 root mean square error. Provided that soil profiles and other ancillary data are known in advance of the cultivation season, capturing drone images in critical growth phases, together with contemporary weather data, can support site- and time-specific harvesting. It could also support site-specific treatments (precision farming) for improving fruit quality in the long-term, with analogous marketing perspectives.

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.

Coffee is a popular beverage that contains various bioactive compounds. However, its molecular mechanism of action is not fully elucidated. In this context, two previously characterized coffee extracts, a lightly roasted and the corresponding green one, were investigated for their effect on nuclear factor erythroid 2‑related factor 2 (Nrf2) target gene expression in myoblasts and endothelial cells using quantitative PCR. The tested concentrations were non‑cytotoxic and led to improved redox cell status, as was evident by increased reduced glutathione (GSH) levels. In both cell lines, the roasted extract upregulated gene expression more readily than its green counterpart leading to increased NAD(P)H quinone dehydrogenase 1 and γ‑glutamyl cysteine ligase catalytic subunit, among others. The green extract had a mixed effect on the endothelial cells, while, as regards the myoblasts it caused the downregulation of some Nrf‑target genes. Therefore, a potential dose‑ and roasting‑dependent mechanism is proposed in the current study, accounting for coffee's antioxidant activity.

Pomegranate has been used therapeutically for centuries. The aim of the present study was to examine the effects of pomegranate juice (PJ) supplementation on complete blood count (CBC), glucose, blood lipids and C-reactive protein (CRP) in healthy subjects. A total of 5 males and 5 females (aged 31.8±6.6 years, weighing 66.2±12.9 kg) were randomly assigned into one of two groups and either consumed 500 ml PJ/day or no PJ for 14 days. Blood samples were obtained from participants prior to and following the experimental period. PJ consumption resulted in a significant increase in red blood cell count (P

The present study focused on the elucidation of the putative anticancer potential of quercetin. The anticancer activity of quercetin at 10, 20, 40, 80 and 120 µM was assessed in vitro by MMT assay in 9 tumor cell lines (colon carcinoma CT-26 cells, prostate adenocarcinoma LNCaP cells, human prostate PC3 cells, pheocromocytoma PC12 cells, estrogen receptor-positive breast cancer MCF-7 cells, acute lymphoblastic leukemia MOLT-4 T-cells, human myeloma U266B1 cells, human lymphoid Raji cells and ovarian cancer CHO cells). Quercetin was found to induce the apoptosis of all the tested cancer cell lines at the utilized concentrations. Moreover, quercetin significantly induced the apoptosis of the CT-26, LNCaP, MOLT-4 and Raji cell lines, as compared to control group (P

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.

Whey protein, a by-product of the cheese industry, can be putatively used as a functional food due to its beneficial health properties. The main objective of the present study was to assess in vivo the effect of a sheep/goat whey protein on the plasma amino acid profile and mammalian target of rapamycin (mTOR), a regulator of skeletal myogenesis. A control group was fed with a standard commercial diet while the experimental group received a standard commercial diet plus sheep/goat whey protein for 28 days. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted to determine plasma amino acid levels while the expression of p70-S6 Kinase 1 (p70-S6K1) in liver and quadriceps muscles was quantified and used as a biomarker of mTOR activity. The results obtained showed a decrease in the levels of essential and branched-chain amino acids (BCAAs) in the experimental group. Furthermore, p70-S6K1 expression was decreased in the liver of rats consumed whey protein. In conclusion, the reduction of amino acid levels and the concomitant inactivation of mTOR imply that whey could potentially act protectively against disorders induced by mTOR overactivation. Intriguingly, this mode of action mimics fasting, an approach with established advantageous health effects.

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.

Excessive production of reactive oxygen species (ROS) may cause endothelial dysfunction and consequently vascular disease. In the present study, the possible protective effects of sheep whey protein (SWP) from tert-butyl hydroperoxide- (tBHP-) induced oxidative stress in endothelial cells (EA.hy926) were assessed using oxidative stress biomarkers. These oxidative stress biomarkers were glutathione (GSH) and ROS levels determined by flow cytometry. Moreover, thiobarbituric acid-reactive substances (TBARS), protein carbonyls (CARB), and oxidized glutathione (GSSG) were determined spectrophotometrically. The results showed that SWP at 0.78, 1.56, 3.12, and 6.24 mg of protein mL−1increased GSH up to 141%, while it decreased GSSG to 46.7%, ROS to 58.5%, TBARS to 52.5%, and CARB to 49.0%. In conclusion, the present study demonstrated for the first time that SWP protected endothelial cells from oxidative stress. Thus, SWP may be used for developing food supplements or biofunctional foods to attenuate vascular disturbances associated with oxidative stress.

The aimof this study is to clarify the effect of cypermethrin (CY) on the oxidative stress (OS) and inflammation status of animals exposed to it and the synergistic role of piperonyl butoxide (PB0).Markers of oxidative stress, such as total antioxidant activity (TAC), protein carbonyls, hemoglobin (Hb), reduced glutathione (GSH), thiobarbituric-acid reactive substances (TBARS), along with the telomerase activity in PBMCs (peripheral blood mononuclear cells) were analyzed.Oxidative stress markers showed statistically significant differences between groups in TAC (p b 0.001), GSH (p = 0.018) and CAT activity (p = 0.029), which depended on dose and combined effect of both compounds. Telomerase activity also showed a statistically significant difference between all groups (F = 43.48, df=6, 14, p b 0.001)with cypermethrin, piperonyl butoxide and the co-exposed groups being significantly different fromthe control group (p b 0.05). Significance: The observed results for TBARS, GSH, Hb, TAC, Crbnls and CAT from our exposed groups showed altered levels compared to control groups that could be linked to doses and combined effects of each chemical substance (cypermethrin and piperonyl butoxide). Oxidative stress markers suggest that cypermethrin, piperonyl butoxide and the co-exposed groups, induce oxidative stress as well as induction of telomerase activity.

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.