Hyperglycemia and hyperlipidemia synergistically and adversely impair insulin secretion and ultimately lead to pancreatic beta cell decomposition. We found that both nutrient overload conditions displace arachidonic and linoleic acids from membrane phospholipids and subject them to free radical-mediated peroxidation and generation of advanced lipid peroxidation end products (ALEs), of which the aldehyde 4-hydroxy-2-nonenal (4-HNE) is prominent. When present at high levels this electrophilic molecule binds covalently to nucleophilic moieties in proteins, phospholipids and nucleic acid, modifies their structure and function and leads to severe cellular dysfunction and apoptosis. However, when present at low and unharmful levels this same molecule activates the nuclear receptor PPARδ and augments insulin secretion. The level of endogenous 4-HNE is determined by the extent of lipid peroxidation on one hand, and by enzymatic neutralization of the aldehyde, on the other. The latter step is mediated by enzymatic processes of which the transformation of the aldehyde to the corresponding inactive carboxylic derivative 4-hydroxy-2-nonenoic acid (4-HNA) is significant. The enzyme responsible for this transformation, which belongs to the large family of aldehyde dehydrogenases and selectively neutralizes fatty acid-derived aldehydes, is ALDH3A2, which is also known as fatty aldehyde dehydrogenase (FALDH). Consequently, we hypothesized that the expression level and function of ALDH3A2 may determine the fate of beta cells under nutrient overload conditions: insufficient neutralization of 4-HNE by the enzyme will lead to cell demise, whereas increased expression and function will extend the adaptive response of beta cells. This adaptive response that is characterized with increased insulin secretion enables effective storage of the nutrient surplus in peripheral tissues and organs while minimizing the dire consequences of the nutrient overload. We aimed at investigating the expression pattern of ALDH3A2 in pancreatic beta cells (the INS-1E cell line) under hyperglycemic condition without or with supplementation with saturated fatty acids (e.g., palmitic acid). Our results show significant glucose- and palmitic acid-dependent induction of ALDH3A2 expression in the cells. We also found that the transformation of palmitic acid (16:1) to mono-unsaturated palmitoleic acid (16:1, cis 9) by the enzyme Stearoyl-CoA desaturase-1 (SCD1) decreased the burden of the lipid stress on the cells and abrogated the stimulus for the induction of ALDH3A2. Preliminary experiments indicated that the upregulation of the induction of ALDH3A2 was partly induced by PPARδ. These findings correlate to our previous discovery that the hormetic effects of 4HNE were mediated via activation of this nuclear receptor. In summary, this study assigns a central role to the enzyme ALDH3A2 in the protective mechanism beta cells employ to mitigate detrimental effects of ALEs, and divert them into hormetic agents, that by feedback mechanism through PPARδ increase ALDH3A2 expression. Full article

Vitamin D₃ has, via its metabolite 1,25-dihydroxyvitaminD₃ (1,25(OH)₂D₃), a high affinity to the transcription factor vitamin D receptor (VDR), and thereby directly affects the epigenome of its target tissues. Changing the transcriptome results in modulation of physiological function, such as calcium homeostasis and the response of innate and adaptive immunity. Genome-wide datasets on the 1,25(OH)₂D₃-triggered binding of VDR, its pioneer factors PU.1 and CEPBA, histone markers and chromatin accessibility in THP-1 human monocytes compared to those obtained in peripheral blood mononuclear cells from vitaminD₃-supplemented human volunteers (VitDbol study) allow the assessment of the epigenome-wide effects of vitamin D. Full article

Oxidative reactions are vital but also cause important stresses and cellular damages resulting in cancers, cardiovascular or neurodegenerative diseases. Antioxidant secondary metabolites from plant can be mobilized for the cell defense and their main source is precisely the food intake such as vegetables, fruits or beverages. Screening natural active metabolites in plants requires different analytical techniques among which mass spectrometry became one of the most popular, not just because of its ability to provide structural information on involved molecules but also because this technique belongs to the arsenal of diagnostic tool for the determination of biological activities. Full article

Ageing is inextricably linked to a deterioration of the musculoskeletal system. This suggests factors governing lifespan might also impact the maintenance of skeletal integrity throughout life. The Oxford Musculoskeletal Ageing group studies the causes and consequences of skeletal ageing. Recent findings indicate dietary constituents (polyphenols, omega 3 fatty acids, polyamines) have the potential to activate longevity mechanisms in vitro and prevent the onset of age-related disorders in vivo. Alterations in RedOx mediators, autophagic flux, sirtuin enzymes and senescence all contribute to an inter-linked ageing nexus manipulated by diet, to maintain health throughout life. Full article

DNA methylation is the most well-known epigenetic modification of DNA. This epigenetic mark is crucial in controlling gene expression profiles, maintaining cellular identity, genomic imprinting and X-chromosome inactivation. Furthermore, DNA methylation is plastic and can adapt to environmental stimuli, acting as a cellular memory of past events. Whereas epigenetic DNA methylation profiling in cancer diagnostics is now well established, associations with other chronic age-associated diseases, including obesity, diabetes, cardiovascular and neurological diseases have recently started to be explored for prognostic, diagnostic and therapeutic applications. Upon genome-wide DNA methylation profiling of whole blood samples from atherosclerotic patients, we characterized various atherosclerosis specific differentially methylated regions (DMRs). Interestingly, similar DMRs were also observed in other age-and inflammation-associated diseases, like obesity, cancer, Alzheimer’s and Parkinson’s disease, both in blood as well as in brain and tumor tissues. This suggests that inflammaging diseases share a common epigenetic signature of the immune system, which is different from the classic epigenetic clock signature. Furthermore, a cardio-protective flavanol-rich diet intervention can partially reverse this inflammaging disease associated epigenetic pattern. We found that this methylation profile mainly reflects shifts in immune cell type composition and infiltrating immune cell populations. Upon correcting for differences in immune cell composition in blood samples, we identified BRCA1 DNA methylation as an atherosclerosis-specific methylation biomarker irrespective of variations in immune cell biomarkers. How BRCA1 DNA methylation differentially promotes cancer, neurodegeneration or atherosclerosis pathologies requires further investigation. In conclusion, atherosclerosis patient blood samples reveal inflammaging and atherosclerosis-specific DNA methylation biomarkers, which could potentially be used as lifestyle biomarkers to estimate disease risk of neurodegeneration, cardiometabolic disorders and cancer in aging populations. Full article

Metabolic syndrome is characterized by an increase in oxidative stress and chronic
low-grade inflammation. The effects of an exercise test at 60–70% of the maximum capacity was
evaluated on inflammatory and antioxidant response in elderly people suffering from metabolic
syndrome. Exercise induced significant increases in plasma levels of inflammatory cytokines and
malondialdehyde. The expression of these cytokines and antioxidant enzymes were also increased
in peripheral blood mononuclear cells. In addition, plasma levels of tumour necrosis factor alpha
were unchanged. In conclusion, the exercise test induces a situation of oxidative stress that
promotes the activation of a proinflammatory cytokine cascade. Full article

Hyperglycemia is a metabolic condition characterized by high blood glucose level due to the disturbances of carbohydrate, lipids and protein metabolism. These disorders lead to impaired of insulin secretion and β-cell dysfunction. It is known that continuous and long-term use of synthetic anti-diabetic drugs can have side effects including hepatic impairment. Thus, the identifications of potent hypoglycemic agents from natural sources of both medicinal and edible plants with minimum side effects, is desirable. Synergetic hypoglycemic activity in experimental animals (rabbits) was shown with ethanol extracts of a mixture of the plant species Hypericum alpestre and Rumex obtusifolius. The chemical composition of these extracts was identified by gas chromatography-mass spectrometry analysis. The plant extracts mixture and natural products extracted from medicinal plant sources have potential for treatment and prevention of diabetes mellitus and metabolic disorders. Full article

Multiple myeloma is a hematological cancer characterized by the clonal proliferation of malignant plasma cells in the bone marrow. That disease has a rather low incidence but displays a high rate of relapse and resistance to conventional therapies. It is therefore necessary to find new therapeutic strategies to overcome this resistance, which is partly attributed to a subpopulation of cells known as cancer stem cells. Withanolides and HDAC6 selective inhibitors were identified as promising compounds in various resistant multiple myeloma models. Full article

The aim of this study is to propose a methodology to assess electrochemical properties of complex mixtures of antioxidants, such as plant extracts, based on the results of simple and popular DPPH test. The first, most difficult step, involves determinations of standard reduction potentials (E⁰) for the series of purified compounds (here catechins). The next step is the calculation of stoichiometric values (n₁₀) based on the results of DPPH test for the same compounds. Finally, a correlation equation is formulated, which is then employed to estimate “cumulative reduction potential” (E_c) for the mixture of interest (here cocoa) using DPPH test results. Full article

Cocoa polyphenols play an important role in protection against diseases in which oxidative stress is implicated as a causal or contributing factor. The main aim of this study was to elucidate the influence of different cocoa extracts and main cocoa bioactive compound (–)-epicatechin on cell growth and support of antioxidant cellular barrier in colon adenocarcinoma cell line model (HT29). Results show that the tested cocoa bioactivity results from concerted interactions between epicatechin and other components. Hence, cocoa is a very good example which supports the food synergy concept that is attracting growing interest. Full article

Although obesity and a sedentary lifestyle are well-known risk factors for type 2 diabetes, at molecular level, the oxidative stress is regarded as the primary contributor to the pathogenic process. Our work intends to evidence how the thinking models influence the way that medical practitioners understand the pathogenic mechanisms. Some research groups focused lately on the system’s dynamics and Complex Systems Theory. The living organisms as a complex system could be analyzed applying the network concept. Alternative methods for characterizing biological processes or phenomena based on feedback node structure have been developed [1]. Full article

The effect of High Pressure Processing (HPP) on Irish potato cultivars’ antioxidant activity (AOA) was examined. High Pressure Processing at 600 MPa for 3 min was applied to two coloured (Rooster and Kerr’s Pink) and two white (Saxon and Gemson) Irish potato varieties. Antioxidant activity was assayed spectrophotometrically by ferric reducing antioxidant power and diphenyl-1-picrylhydrazyl methods. No statistically significant (p ≥ 0.05) change in antioxidant activity was observed in both the AOA methods irrespective of the HPP treatments, although a slight increase in the activity was noted in the majority of the HPP treated samples. This implies that HPP treatment has little role in improving the functional qualities, and can be tailored to improve the quality and safety of the commonly consumed potatoes. Full article

FOXO (Forkhead box, class O) proteins are transcriptional regulators ubiquitously expressed in mammalian cells with roles in modulating fuel metabolism, stress resistance and cell death. FOXO transcription factors are regulated by redox processes at several levels, including enzymatic and nonenzymatic posttranslational modification. Target genes controlled by FOXO proteins include genes encoding antioxidant proteins, thus likely contributing to the key role FOXOs play in the cellular response to oxidative stress. Here, an overview is provided on (i) the modulation of FOXO proteins by thiol depleting agents, (ii) consequences of thiol depletion for stress resistance and life span of a model organism, Caenorhabditis elegans and (iii) the role of FOXO proteins therein. Full article

The vitamin B3 (niacin) is present in various foods. During roasting of green coffee beans, niacin is formed from the alkaloid trigonelline. Therefore, we established a novel fast and sensitive HPLC-MS/MS method to determine niacin in coffee brews from five commercially available coffee samples. Additionally, we investigated the influence of the brewing method, brewing temperature, and degree of roasting on niacin contents. In the respective coffee brews, we were able to show that the content of niacin in coffee beverages is not only affected by the degree of roasting, but also by the extraction performance of different brewing methods to a lesser extent. Full article

As a physiological nitric oxide donor, S-nitrosoglutathione (GSNO) is a promising candidate for several diseases (e.g., stroke and atherosclerosis). However, its clinical application has been limited by its low stability. In order to protect GSNO suitable for oral route administration and to achieve sustained release, 3 different particles from nano-size to micro-size were obtained by a water-in-oil-in-water (W/O/W) or solid-in-oil-in-water (S/O/W) double emulsion/solvent evaporation method. The 3 different particles tuned out to have similar encapsulation efficiency while the microparticles showed longer release time. Finally, the 3 formulations have been successfully lyophilized for long term stability. Full article

Cardiovascular diseases are associated with oxidative stress and a reduced bioavailability of nitric oxide (NO). To counteract both processes, the administration of S-nitrosoglutathione (GSNO) can be envisaged. GSNO is able to induce protein S-nitrosation (Pr-SNO), which is a post-translational modification of proteins, participating in the storage of NO in tissues, and protect thiol functions from oxidation. However, GSNO antioxidant power is poorly studied, which is probably linked to its low stability. This low stability can be addressed by nanotechnologies that will increase GSNO protection and provide a sustained release of the drug. Full article

There is now strong evidence that the redox environment inside cells is very different to that outside the cell, and that many extracellular environments are both more oxidizing and also subject to extensive oxidation. This difference in redox environments results in significant changes in oxidation chemistry and biology, altered redox equilibria, and antioxidant defense mechanisms. It is also increasingly apparent that oxidation events both inside and outside cells (extracellular oxidation) play a critical role in driving many diseases. Many extracellular proteins are highly abundant, long-lived and relatively poorly protected against damage. They can therefore accumulate high levels of modification during ageing and chronic disease, resulting in their use as biomarkers of long-term oxidative stress. Furthermore, increasing evidence supports the hypothesis that oxidized extracellular matrix materials play a key role in determining cell function and fate. Full article

Winery by-products, including pomace, stem, vine leaves and shoots, arise in high amounts during the wine-making process. Due to high contents of secondary plant metabolites, such as polyphenols, their usage in the food, cosmetics and pharmaceutical industry is possible. In this study, we investigated effects of an extract prepared from vine shoots (Vitis vinifera L. cv. Riesling) on riboflavin-induced DNA damage in human hepatocellular carcinoma cells HepG2 by comet assay. Significant decreases of DNA damages were detected after 2 h and 24 h extract incubation at concentration ranges of 1 to 30 µg/mL (2 h) and 1 to 10 µg/mL (24 h), respectively. These effects may be attributable to polyphenolic compounds, which has to be further investigated. Full article

The impact of catechins on the expression profile of redox-related genes in HT29 cell line has been studied recently by our group using Oxidative Stress RT2 Profiler PCR Array. Within the examined panel of 84 genes, the down-regulation of SRXN1 gene was unique among other up-regulated genes. We hypothesized that the observed down-regulation resulted from DNA methylation and have exploited this observation to choose the proper strategy to monitor the changes in DNA methylation patterns incurred by dietary antioxidants. The current study verified two PCR-based approaches. Full article

Silybum marianum fruit extract silymarin displays various biological activities, which are attributed mostly to its major component silybin. However, silymarin contain several other isomeric flavonolignans (isosilybin, silychristin, silydianin) and their oxidation products, the 2,3-dehydroflavonolignans (2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3-dehydrosilydianin). The latter compounds were found to be 1-2 orders of magnitude more efficient radical scavengers, reducing, chelating, cytoprotective, anti-aging, anti-cancer and anti-angiogenic agents than the parent flavonolignans. Although 2,3-dehydroflavonolignans occur in silymarin as minorities, they seem to be responsible for the majority of the biological activity and therefore have potential for the prevention of chronic diseases. Full article

Pancreatic adenocarcinoma mainly occurs in elderly people. Thus, the management of pancreatic cancer in the aging population is becoming increasingly relevant. In this preliminary study we evaluated the effect of selected phytochemicals and their combinations on the expression and activation of Nrf2 transcription factor in the human pancreatic cancer cell line MIA-Pa-Ca-2. Treatment for 24 h with xanthohumol (X), resveratrol (RES), indole-3-carbinol (I3C) or phenethyl isothiocyanate (PEITC) had no effect on the expression and activation of Nrf2, or the expression of the SOD gene controlled by Nrf2. However, combinations of these phytochemicals significantly increased Nrf2 activation and subsequently the expression of SOD. The most efficient were the mixtures of resveratrol and glucosinolates degradation products, I3C and PEITC. These results indicate that combinations of phytochemicals resembling that occurring in natural diets may efficiently modulate the signaling pathways, whose proper function is important for pancreatic cancer prophylaxis or improving the results of conventional therapy. Full article

Voltammetric methods—cyclic (CV) and differential pulse voltammetry (DPV) are considered the most appropriate way to evaluate antioxidant activity of redox active compounds. They provide information about both mechanism and kinetics of electrochemical oxidation of antioxidants as well as their physical and chemical properties such as the redox potential or the number of electrons transferred. These methods are helpful for understanding the mechanisms of oxidation or reduction processes of antioxidant compounds. This work presents the electrochemical properties of vitamin C obtained by both CV and DPV methods. Full article

Numerous secondary metabolites found in edible plants modulate intracellular redox processes and are suggested to prevent certain diseases, especially in ageing organisms. Since such nutraceuticals provide the basis for new and innovative designer diets and therapies, extracting these substances and their potential from plants has become a focus of research, with nanotechnology and natural nanoparticles at the centre of some of these developments. Full article

Flavonoids are polyphenolic compounds commonly found in plants. As dietary components, they have been shown to exhibit numerous pro-health properties that are believed to be associated with their antioxidant effects. In this study, the antioxidant activity of four flavonoid compounds was determined by cellular antioxidant activity assay using HT29 cells as a model of the alimentary tract. The strongest impact on cellular redox status was observed for aglycones which acted as both antioxidants (quercetin) and prooxidants (naringenin). Interestingly, mixtures of tested compounds displayed only antioxidative properties. Full article

Garlic is a common ingredient in food, normally used as spice but is also used since ancient times for its health beneficial activity. The thiosulfinate allicin is the first active compound in freshly damaged garlic tissue and reacts with thiol-groups. Hence, allicin is able to modify thiol groups, both of protein cysteine-residues and low-molecular weight thiols like glutathione. This thiol-modification is supposed to be an important mechanism for allicin’s biological activity. Here, the mechanisms and possible targets for allicin in cells are discussed. Full article

Hydroquinone (HQ) is a phenolic metabolite of benzene, which is used as a skin whitener. Insects synthesize this natural compound as a deterrent and mushrooms as a toxin. Pro-apoptotic effects of HQ were previously documented on various cancer cell types. Here we investigated the cell-death inducing mechanisms of this compound in chronic myeloid leukemia cell models. Full article

It has been believed that the metabolism of xenobiotics occurred mainly by the cytochrome P450 enzyme system in the liver. However, recent data clearly suggest a significant role for the gut microbiota in the metabolism of xenobiotic compounds. This microbiotic biotransformation could lead to differences on activation, inactivation and possible toxicity of these compounds. In vitro models are generally used to study the colonic biotransformation as they allow easy dynamic and multiple sampling over time. However, to ensure this accurately mimics communities in vivo, the pre-analytical phase requires optimization. Chlorogenic acid, a polyphenolic compound abundantly present in the human diet, was used as a model compound to optimize a ready-to-use gut microbiome biotransformation platform. Samples of the in vitro gastrointestinal dialysis-model with colon stage were analyzed by liquid chromatography coupled to high resolution time-of-flight mass spectrometry. Complementary screening approaches were also employed to identify the biotransformation products. Full article

Ageing is a complex process affected by both genetic and environmental factors, characterized by a gradual failure of functionality, reduced stress response and resistance, leading to enhanced probability for age-related diseases and mortality. During the last decades, natural compounds have attracted the attention of researchers in the quest of bioactive phytochemicals with anti-ageing properties. For a few of these compounds an extra advantage appears; many of them have been shown to decelerate the progression of age-related diseases with emphasis on aggregation-related diseases. Using the nematode Caenorhabditis elegans along with the replicative senescence model of human primary fibroblasts, we have identified compounds that are part of our diet with anti-oxidation, anti-ageing and anti-aggregation activities. Some of the identified compounds promote their anti-ageing activity through activation of the proteasome, others through the activation of Nrf2 transcription factor, while others through inhibition of glucose transporters (GLUTs). Our work identifies new bioactive compounds with anti-ageing and/or anti-aggregation properties or reveals additional beneficial properties on already known bioactive compounds. Full article

Whey proteins are highly valued food ingredients. This study examines the health benefits to muscle cells of six individual whey peptides known to cross the intestinal barrier. Results indicate that peptides KVPQ, NLPPL, VAGT, VGIN and PVPQ protect undifferentiated C2C12 myoblasts from free radical damage. Full article