Publications by authors named "Evangelia Sarandi"

14 Publications

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The snapshot of metabolic health in evaluating micronutrient status, the risk of infection and clinical outcome of COVID-19.

Clin Nutr ESPEN 2021 Aug 26;44:173-187. Epub 2021 Jun 26.

Metabolomic Medicine, Health Clinic for Autoimmune and Chronic Diseases, 10674 Athens, Greece. Electronic address:

COVID-19 has re-established the significance of analyzing the organism through a metabolic perspective to uncover the dynamic interconnections within the biological systems. The role of micronutrient status and metabolic health emerge as pivotal in COVID-19 pathogenesis and the immune system's response. Metabolic disruption, proceeding from modifiable factors, has been proposed as a significant risk factor accounting for infection susceptibility, disease severity and risk for post-COVID complications. Metabolomics, the comprehensive study and quantification of intermediates and products of metabolism, is a rapidly evolving field and a novel tool in biomarker discovery. In this article, we propose that leveraging insulin resistance biomarkers along with biomarkers of micronutrient deficiencies, will allow for a diagnostic window and provide functional therapeutic targets. Specifically, metabolomics can be applied as: a. At-home test to assess the risk of infection and propose nutritional support, b. A screening tool for high-risk COVID-19 patients to develop serious illness during hospital admission and prioritize medical support, c(i). A tool to match nutritional support with specific nutrient requirements for mildly ill patients to reduce the risk for hospitalization, and c(ii). for critically ill patients to reduce recovery time and risk of post-COVID complications, d. At-home test to monitor metabolic health and reduce post-COVID symptomatology. Metabolic rewiring offers potential virtues towards disease prevention, dissection of high-risk patients, taking actionable therapeutic measures, as well as shielding against post-COVID syndrome.
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http://dx.doi.org/10.1016/j.clnesp.2021.06.011DOI Listing
August 2021

Application of Metabolomics in Pediatric Asthma: Prediction, Diagnosis and Personalized Treatment.

Metabolites 2021 Apr 18;11(4). Epub 2021 Apr 18.

European Institute of Nutritional Medicine, 00198 Rome, Italy.

Asthma in children remains a significant public health challenge affecting 5-20% of children in Europe and is associated with increased morbidity and societal healthcare costs. The high variation in asthma incidence among countries may be attributed to differences in genetic susceptibility and environmental factors. This respiratory disorder is described as a heterogeneous syndrome of multiple clinical manifestations (phenotypes) with varying degrees of severity and airway hyper-responsiveness, which is based on patient symptoms, lung function and response to pharmacotherapy. However, an accurate diagnosis is often difficult due to diversities in clinical presentation. Therefore, identifying early diagnostic biomarkers and improving the monitoring of airway dysfunction and inflammatory through non-invasive methods are key goals in successful pediatric asthma management. Given that asthma is caused by the interaction between genes and environmental factors, an emerging approach, metabolomics-the systematic analysis of small molecules-can provide more insight into asthma pathophysiological mechanisms, enable the identification of early biomarkers and targeted personalized therapies, thus reducing disease burden and societal cost. The purpose of this review is to present evidence on the utility of metabolomics in pediatric asthma through the analysis of intermediate metabolites of biochemical pathways that involve carbohydrates, amino acids, lipids, organic acids and nucleotides and discuss their potential application in clinical practice. Also, current challenges on the integration of metabolomics in pediatric asthma management and needed next steps are critically discussed.
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http://dx.doi.org/10.3390/metabo11040251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072856PMC
April 2021

Metabolic profiling of organic and fatty acids in chronic and autoimmune diseases.

Adv Clin Chem 2021 15;101:169-229. Epub 2020 Jul 15.

Metabolomic Medicine Clinic, Athens, Greece; European Institute of Nutritional Medicine, E.I.Nu.M, Rome, Italy. Electronic address:

Metabolomics is a powerful tool of omics that permits the simultaneous identification of metabolic perturbations in several autoimmune and chronic diseases. Several parameters can affect a metabolic profile, from the population characteristics to the selection of the analytical method. In the current chapter, we summarize the main analytical methods and results of the metabolic profiling of fatty and organic acids performed in human metabolomic studies for asthma, COPD, psoriasis and Hashimoto's thyroiditis. We discuss the most significant metabolic alterations associated with these diseases, after comparison of either a single patient's group with healthy controls or several patient's subgroups of different disease severity and phenotype with healthy controls or of a patient's group before and after treatment. Finally, we present critical metabolic patterns that are associated with each disease and their potency for the unraveling of disease pathogenesis, prediction, diagnosis, patient stratification and treatment selection.
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http://dx.doi.org/10.1016/bs.acc.2020.06.003DOI Listing
July 2021

Telomerase and telomeres in aging theory and chronographic aging theory (Review).

Mol Med Rep 2020 Sep 25;22(3):1679-1694. Epub 2020 Jun 25.

Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece.

The current review focuses on the connection of telomerase and telomeres with aging. In this review, we describe the changes in telomerase and telomere length (TEL) during development, their role in carcinogenesis processes, and the consequences of reduced telomerase activity. More specifically, the connection of TEL in peripheral blood cells with the development of aging‑associated diseases is discussed. The review provides systematic data on the role of telomerase in mitochondria, the biology of telomeres in stem cells, as well as the consequences of the forced expression of telomerase (telomerization) in human cells. Additionally, it presents the effects of chronic stress exposure on telomerase activity, the effect of TEL on fertility, and the effect of nutraceutical supplements on TEL. Finally, a comparative review of the chronographic theory of aging, presented by Olovnikov is provided based on currently available scientific research on telomere, telomerase activity, and the nature of aging by multicellular organisms.
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http://dx.doi.org/10.3892/mmr.2020.11274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411297PMC
September 2020

Analysis of the intricate effects of polyunsaturated fatty acids and polyphenols on inflammatory pathways in health and disease.

Food Chem Toxicol 2020 Sep 5;143:111558. Epub 2020 Jul 5.

Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003, Heraklion, Greece; Department of Analytical and Forensic Medical Toxicology, Sechenov University, 2-4 Bolshaya Pirogovskaya st, 119991, Moscow, Russia. Electronic address:

Prevention and treatment of non-communicable diseases (NCDs), including cardiovascular disease, diabetes, obesity, cancer, Alzheimer's and Parkinson's disease, arthritis, non-alcoholic fatty liver disease and various infectious diseases; lately most notably COVID-19 have been in the front line of research worldwide. Although targeting different organs, these pathologies have common biochemical impairments - redox disparity and, prominently, dysregulation of the inflammatory pathways. Research data have shown that diet components like polyphenols, poly-unsaturated fatty acids (PUFAs), fibres as well as lifestyle (fasting, physical exercise) are important factors influencing signalling pathways with a significant potential to improve metabolic homeostasis and immune cells' functions. In the present manuscript we have reviewed scientific data from recent publications regarding the beneficial cellular and molecular effects induced by dietary plant products, mainly polyphenolic compounds and PUFAs, and summarize the clinical outcomes expected from these types of interventions, in a search for effective long-term approaches to improve the immune system response.
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http://dx.doi.org/10.1016/j.fct.2020.111558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335494PMC
September 2020

Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors.

Int J Environ Res Public Health 2020 06 10;17(11). Epub 2020 Jun 10.

Department Forensic Sciences and Toxicology, University of Crete, Faculty of Medicine, 71003 Heraklion, Greece.

The lifestyle adopted by most people in Western societies has an important impact on the propensity to metabolic disorders (e.g., diabetes, cancer, cardiovascular disease, neurodegenerative diseases). This is often accompanied by chronic low-grade inflammation, driven by the activation of various molecular pathways such as STAT3 (signal transducer and activator of transcription 3), IKK (IκB kinase), MMP9 (matrix metallopeptidase 9), MAPK (mitogen-activated protein kinases), COX2 (cyclooxigenase 2), and NF-Kβ (nuclear factor kappa-light-chain-enhancer of activated B cells). Multiple intervention studies have demonstrated that lifestyle changes can lead to reduced inflammation and improved health. This can be linked to the concept of real-life risk simulation, since humans are continuously exposed to dietary factors in small doses and complex combinations (e.g., polyphenols, fibers, polyunsaturated fatty acids, etc.). Inflammation biomarkers improve in patients who consume a certain amount of fiber per day; some even losing weight. Fasting in combination with calorie restriction modulates molecular mechanisms such as m-TOR, FOXO, NRF2, AMPK, and sirtuins, ultimately leads to significantly reduced inflammatory marker levels, as well as improved metabolic markers. Moving toward healthier dietary habits at the individual level and in publicly-funded institutions, such as schools or hospitals, could help improving public health, reducing healthcare costs and improving community resilience to epidemics (such as COVID-19), which predominantly affects individuals with metabolic diseases.
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http://dx.doi.org/10.3390/ijerph17114135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312944PMC
June 2020

Telomere length and telomerase activity in osteoporosis and osteoarthritis.

Exp Ther Med 2020 Mar 24;19(3):1626-1632. Epub 2019 Dec 24.

Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece.

Osteoarthritis (OA) and osteoporosis (OP) are associated skeletal pathologies and have as a distinct feature the abnormal reconstruction of the subchondral bone. OA and OP have been characterized as age-related diseases and have been associated with telomere shortening and altered telomerase activity (TA). This review discusses the role of telomeres and telomerase in OA and OP pathologies and focuses on the usability of telomere length (TL) and the rate of telomere shortening as potential disease biomarkers. A number of studies have demonstrated that telomere shortening may contribute to OA and OP as an epigenetic factor. Therefore, it has been claimed that the measurement of TL of chondrocytes and/or peripheral blood cells may be an appropriate marker for the evaluation of the progression of these diseases. However, there is a need to be perform further studies with larger cohorts, with the aim of obtaining objective results and a better understanding of the association between TL, inflammation and aging, in order to provide further insight into the pathophysiology of degenerative joint diseases.
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http://dx.doi.org/10.3892/etm.2019.8370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027092PMC
March 2020

Metabolic Fingerprint of Chronic Obstructive Lung Diseases: A New Diagnostic Perspective.

Metabolites 2019 Nov 26;9(12). Epub 2019 Nov 26.

Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece.

Chronic obstructive lung disease (COLD) is a group of airway diseases, previously known as emphysema and chronic bronchitis. The heterogeneity of COLD does not allow early diagnosis and leads to increased morbidity and mortality. The increasing number of COLD incidences stresses the need for precision medicine approaches that are specific to the patient. Metabolomics is an emerging technology that allows for the discrimination of metabolic changes in the cell as a result of environmental factors and specific genetic background. Thus, quantification of metabolites in human biofluids can provide insights into the metabolic state of the individual in real time and unravel the presence of, or predisposition to, a disease. In this article, the advantages of and potential barriers to putting metabolomics into clinical practice for COLD are discussed. Today, metabolomics is mostly lab-based, and research studies with novel COLD-specific biomarkers are continuously being published. Several obstacles in the research and the market field hamper the translation of these data into clinical practice. However, technological and computational advances will facilitate the clinical interpretation of data and provide healthcare professionals with the tools to prevent, diagnose, and treat COLD with precision in the coming decades.
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http://dx.doi.org/10.3390/metabo9120290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949962PMC
November 2019

Targeted Metabolomic Analysis of Serum Fatty Acids for the Prediction of Autoimmune Diseases.

Front Mol Biosci 2019 1;6:120. Epub 2019 Nov 1.

Department of Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy, Craiova, Romania.

Autoimmune diseases (ADs) are rapidly increasing worldwide and accumulating data support a key role of disrupted metabolism in ADs. This study aimed to identify an improved combination of Total Fatty Acids (TFAs) biomarkers as a predictive factor for the presence of autoimmune diseases. A retrospective nested case-control study was conducted in 403 individuals. In the case group, 240 patients diagnosed with rheumatoid arthritis, thyroid disease, multiple sclerosis, vitiligo, psoriasis, inflammatory bowel disease, and other AD were included and compared to 163 healthy individuals. Targeted metabolomic analysis of serum TFAs was performed using GC-MS, and 28 variables were used as input for the predictive models. The primary analysis identified 12 variables that were statistically significantly different between the two groups, and metabolite-metabolite correlation analysis revealed 653 significant correlation coefficients with 90% level of significance ( < 0.05). Three predictive models were developed, namely (a) a logistic regression based on Principal Component Analysis (PCA), (b) a straightforward logistic regression model and (c) an Artificial Neural Network (ANN) model. PCA and straightforward logistic regression analysis, indicated reasonably well adequacy (74.7 and 78.9%, respectively). For the ANN, a model using two hidden layers and 11 variables was developed, resulting in 76.2% total predictive accuracy. The models identified important biomarkers: lauric acid (C12:0), myristic acid (C14:0), stearic acid (C18:0), lignoceric acid (C24:0), palmitic acid (C16:0) and heptadecanoic acid (C17:0) among saturated fatty acids, Cis-10-pentadecanoic acid (C15:1), Cis-11-eicosenoic acid (C20:1n9), and erucic acid (C22:1n9) among monounsaturated fatty acids and the Gamma-linolenic acid (C18:3n6) polyunsaturated fatty acid. The metabolic pathways of the candidate biomarkers are discussed in relation to ADs. The findings indicate that the metabolic profile of serum TFAs is associated with the presence of ADs and can be an adjunct tool for the early diagnosis of ADs.
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http://dx.doi.org/10.3389/fmolb.2019.00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839420PMC
November 2019

Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives.

Mol Med Rep 2019 Oct 23;20(4):3701-3708. Epub 2019 Aug 23.

Department of Clinical Pharmacy, University of Medicine and Pharmacy, Faculty of Pharmacy, 200349 Craiova, Romania.

Telomere length, a marker of cellular aging, decreases with age and it has been associated with aging‑related diseases. Environmental factors, including diet and lifestyle factors, affect the rate of telomere shortening which can be reversed by telomerase. Telomerase activation by natural molecules has been suggested to be an anti‑aging modulator that can play a role in the treatment of aging‑related diseases. This study aimed to investigate the effect of natural compounds on telomerase activity in human peripheral blood mononuclear cells (PBMCs). The tested compounds included Centella asiatica extract formulation (08AGTLF), Astragalus extract formulation (Nutrient 4), TA‑65 (containing Astragalus membranaceus extract), oleanolic acid (OA), maslinic acid (MA), and 3 multi‑nutrient formulas (Nutrients 1, 2 and 3) at various concentrations. The mean absorbance values of telomerase activity measured following treatment with some of the above‑mentioned formulations were statistically significantly higher compared to those of the untreated cells. In particular, in order of importance with respect to telomerase activation from highest to lowest, 08AGTLF, OA, Nutrient 4, TA‑65, MA, Nutrient 3 and Nutrient 2, triggered statistically significant increase in telomerase activity compared to the untreated cells. 08AGTLF reached the highest levels of telomerase activity reported to date, at least to our knowledge, increasing telomerase activity by 8.8 folds compared to untreated cells, while Nutrient 4 and OA were also potent activators (4.3‑fold and 5.9‑fold increase, respectively). On the whole, this study indicates that the synergistic effect of nutrients and natural compounds can activate telomerase and produce more potent formulations. Human clinical studies using these formulations are required to evaluate their mode of action. This would reveal the health benefits of telomerase activation through natural molecules and would shed new light onto the treatment of aging‑related diseases.
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http://dx.doi.org/10.3892/mmr.2019.10614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755196PMC
October 2019

Association of nutraceutical supplements with longer telomere length.

Int J Mol Med 2019 Jul 10;44(1):218-226. Epub 2019 May 10.

Department of Clinical Pharmacy, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova 200349, Romania.

Telomeres are nucleotide tandem repeats located at the tip of eukaryotic chromosomes that maintain genomic integrity. The gradual shortening of telomeres leads to cellular senescence and apoptosis, a key mechanism of aging and age‑related chronic diseases. Epigenetic factors, such as nutrition, exercise and tobacco can affect the rate at which telomeres shorten and can modify the risk of developing chronic diseases. In this study, we evaluated the effects of a combination of nutraceutical supplements (NS) on telomere length (TL) in healthy volunteers with no medical history of any disease. Participants (n=47) were selected from healthy outpatients visiting a private clinic and were divided into the experimental group (n=16), that received the NS and the control group (n=31). We estimated the length of single telomeres in metaphase spread leukocytes, isolated from peripheral blood, using quantitative‑fluorescent in situ hybridization (Q‑FISH) analysis. The length of the whole telomere genome was significantly increased (P<0.05) for the mean, 1st quartile and median measurements in the experimental group. Similar findings were observed for short TL (20th percentile) (P<0.05) for the median and 3rd quartile measurements in the NS group, compared to the control group. The beneficial effects of the supplements on the length of short telomeres remained significant (P<0.05) following adjustment for age and sex. Telomeres were moderately longer in female patients compared to the male patients. On the whole, the findings of this study suggest that the administration of NS may be linked to sustaining the TL.
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http://dx.doi.org/10.3892/ijmm.2019.4191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559326PMC
July 2019

Developing BIOTEL: A Semi-Automated Spreadsheet for Estimating Telomere Length and Biological Age.

Front Genet 2019 19;10:84. Epub 2019 Feb 19.

Laboratory of Toxicology, Medical School, University of Crete, Heraklion, Greece.

Telomere length (TL) is causally related to aging and several age-related diseases. Specifically, the abundance of short telomeres and the rate of telomere shortening are strong determinants of cell homeostasis. Thus, tools for analyzing and manipulating TL data can vastly improve research focused on aging. Aim: In this study, we developed a semi-automated worksheet, BIOTEL, to generate individual and group TL statistics and provide a crude estimation of biological age. Data from the Telomere Length Database Project (TLDP) were implemented to the spreadsheet to produce TL statistics. 150 participants were included, and their age was from 21 to 82 years, and the sex distribution ratio was 52.3%: 47.7% (male: female). Initially, we analyzed the fluorescence intensities of telomeres that were measured on metaphase spread leukocytes using three-dimensional (3D) quantitative-fluorescent hybridization (Q-FISH) procedures (3D DNA FISH) with a (C3TA2)3 peptide nucleic acid (PNA) probe. Raw data of fluorescence intensities, demographic data and medical records from the participants were imported into the worksheet. Basic statistical analyses of TL data were provided through BIOTEL, including TL percentiles, specialized charts for TL distribution including the percentage of critically short telomeres (< 3,000 kilobases), individual telomere profiles, and graphs of biological age vs. chronological age. BIOTEL ver. 2.4 is a functional semi-automated worksheet that calculates a wide range of TL statistics, thus a useful tool with applications in research of telomeres and biological age estimation.
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http://dx.doi.org/10.3389/fgene.2019.00084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389611PMC
February 2019

Application of metabolomics part II: Focus on fatty acids and their metabolites in healthy adults.

Int J Mol Med 2019 Jan 14;43(1):233-242. Epub 2018 Nov 14.

Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece.

Fatty acids (FAs) play critical roles in health and disease. The detection of FA imbalances through metabolomics can provide an overview of an individual's health status, particularly as regards chronic inflammatory disorders. In this study, we aimed to establish sensitive reference value ranges for targeted plasma FAs in a well‑defined population of healthy adults. Plasma samples were collected from 159 participants admitted as outpatients. A total of 24 FAs were analyzed using gas chromatography‑mass spectrometry, and physiological values and 95% reference intervals were calculated using an approximate method of analysis. The differences among the age groups for the relative levels of stearic acid (P=0.005), the omega‑6/omega‑3 ratio (P=0.027), the arachidonic acid/eicosapentaenoic acid ratio (P<0.001) and the linoleic acid‑produced dihomo‑gamma‑linolenic acid (P=0.046) were statistically significant. The majority of relative FA levels were higher in males than in females. The levels of myristic acid (P=0.0170) and docosahexaenoic acid (P=0.033) were significantly different between the sexes. The reference values for the FAs examined in this study represent a baseline for further studies examining the reproducibility of this methodology and sensitivities for nutrient deficiency detection and investigating the biochemical background of pathological conditions. The application of these values to clinical practice will allow for the discrimination between health and disease and contribute to early prevention and treatment.
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http://dx.doi.org/10.3892/ijmm.2018.3989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257830PMC
January 2019
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