Publications by authors named "Aristides Tsatsakis"

110 Publications

Genetic and Epigenetic Alterations Induced by Pesticide Exposure: Integrated Analysis of Gene Expression, microRNA Expression, and DNA Methylation Datasets.

Int J Environ Res Public Health 2021 08 17;18(16). Epub 2021 Aug 17.

Epidemiology and Biostatistics Unit, National Cancer Institute-IRCCS 'Fondazione G. Pascale', 80131 Naples, Italy.

Environmental or occupational exposure to pesticides is considered one of the main risk factors for the development of various diseases. Behind the development of pesticide-associated pathologies, there are both genetic and epigenetic alterations, where these latter are mainly represented by the alteration in the expression levels of microRNAs and by the change in the methylation status of the DNA. At present, no studies have comprehensively evaluated the genetic and epigenetic alterations induced by pesticides; therefore, the aim of the present study was to identify modifications in gene miRNA expression and DNA methylation useful for the prediction of pesticide exposure. For this purpose, an integrated analysis of gene expression, microRNA expression, and DNA methylation datasets obtained from the GEO DataSets database was performed to identify putative genes, microRNAs, and DNA methylation hotspots associated with pesticide exposure and responsible for the development of different diseases. In addition, DIANA-miRPath, STRING, and GO Panther prediction tools were used to establish the functional role of the putative biomarkers identified. The results obtained demonstrated that pesticides can modulate the expression levels of different genes and induce different epigenetic alterations in the expression levels of miRNAs and in the modulation of DNA methylation status.
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http://dx.doi.org/10.3390/ijerph18168697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394939PMC
August 2021

The EU chemicals strategy for sustainability: in support of the BfR position.

Arch Toxicol 2021 09 7;95(9):3133-3136. Epub 2021 Aug 7.

Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit, Amsterdam, The Netherlands.

The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved. A continuous process of improvement in consumer protection is clearly desirable but any initiative directed towards this objective must be based on scientific knowledge. It must not confound risk with other factors in determining policy. This conclusion is fully supported in the present Commentary including the request to improve both, data collection and the time-consuming and bureaucratic procedures that delay the publication of regulations.
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http://dx.doi.org/10.1007/s00204-021-03125-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380226PMC
September 2021

The state of the scientific revolution in toxicology.

ALTEX 2021 17;38(3):379-386. Epub 2021 Jun 17.

University of Crete, Medical School, Toxicology Science and Research Centre in the Department of Forensic Sciences, Crete, Greece.

Science changes in waves, the so-called paradigm shifts or scientific revolutions. This concept was prominently elabo­rated by Thomas S. Kuhn more than 50 years ago in what remains one of the most cited science philosophy books of all time. Kuhn described how “normal science” experiences anomalies, which bring it to crisis and revolution from which a new, immature scientific paradigm results, which over time becomes the new normal. Building on an analysis on how this applies to toxicology and its change in approach in 2008, we concluded at the time that toxicology had encountered a number of such anomalies and was moving into crisis. Here, the progress along Kuhn’s trajectory over the last 12 years of a scientific revolution is discussed. We conclude that this decade has shown up even more anomalies, and the perception of crisis has spread and consolidated. Indications of revolutionary paradigm changes are emerging.
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http://dx.doi.org/10.14573/altex.2106101DOI Listing
June 2021

Ameliorative Effects of the Sesquiterpenoid Valerenic Acid on Oxidative Stress Induced in HepG2 Cells after Exposure to the Fungicide Benomyl.

Antioxidants (Basel) 2021 May 8;10(5). Epub 2021 May 8.

Center of Toxicology Science and Research, Medical School, University of Crete, 71003 Heraklion, Greece.

Valerenic acid (VA) is a sesquiterpenoid and a phytoconstituent of the plant valerian used for sleeping disorders and anxiety. The frequency of using herbal components as therapeutic nutritional agents has increased lately. Their ability to improve redox homeostasis makes them a valuable approach against harmful xenobiotics. The purpose of this study was to evaluate the putative beneficial role of VA against the redox-perturbating role of the fungicide benomyl in HepG2 human liver cells in terms of oxidative stress in the cellular environment and in endoplasmic reticulum (ER). Benomyl increased cell total oxidant status and reactive oxygen species production and decreased total antioxidant status. The expression of genes coding for antioxidant molecules, namely, heme oxygenase-1, alpha glutathione s-transferase, NF-ĸB, and liver fatty acid binding protein, were decreased due to benomyl. VA ameliorated these effects. Benomyl also increased ER-stress-related molecules such as endoplasmic reticulum to nucleus signaling 1 protein, glucose-regulated protein 78, and caspase-12 levels, and VA acted also as a preventive agent. These results indicate that VA exerts ameliorative effects after benomyl-induced oxidative stress. VA, a widely used nutritional supplement, is a compound with potent antioxidant properties, which are valuable for the protection of cells against xenobiotic-induced oxidative damage.
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http://dx.doi.org/10.3390/antiox10050746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151918PMC
May 2021

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, 150003 Yaroslavl, Russia.

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.
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http://dx.doi.org/10.3390/ijms22094646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124173PMC
April 2021

Serum Zinc, Copper, and Other Biometals Are Associated with COVID-19 Severity Markers.

Metabolites 2021 Apr 15;11(4). Epub 2021 Apr 15.

World-Class Research Center "Digital Biodesign and Personalized Healthcare", IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia.

The objective of the present study was to evaluate of serum metal levels in COVID-19 patients with different disease severity, and to investigate the independent association between serum metal profile and markers of lung damage. The cohort of COVID-19 patients consisted of groups of subjects with mild, moderate, and severe illness, 50 examinees each. Forty-four healthy subjects of the respective age were involved in the current study as the control group. Serum metal levels were evaluated using inductively-coupled plasma mass-spectrometry. Examination of COVID-19 patients demonstrated that heart rate, respiratory rate, body temperature, C-reactive protein levels, as well as lung damage increased significantly with COVID-19 severity, whereas SpO decreased gradually. Increasing COVID-19 severity was also associated with a significant gradual decrease in serum Ca, Fe, Se, Zn levels as compared to controls, whereas serum Cu and especially Cu/Zn ratio were elevated. No significant group differences in serum Mg and Mn levels were observed. Serum Ca, Fe, Se, Zn correlated positively with SpO, being inversely associated with fever, lung damage, and C-reactive protein concentrations. Opposite correlations were observed for Cu and Cu/Zn ratio. In regression models, serum Se levels were inversely associated with lung damage independently of other markers of disease severity, anthropometric, biochemical, and hemostatic parameters. Cu/Zn ratio was also considered as a significant predictor of lower SpO in adjusted regression models. Taken together, these findings demonstrated that metal metabolism significantly interferes with COVID-19 pathogenesis, although the causal relations as well as precise mechanisms are yet to be characterized.
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http://dx.doi.org/10.3390/metabo11040244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071197PMC
April 2021

Social injustice in environmental health: A call for fortitude.

Environ Res 2021 03 26;194:110675. Epub 2020 Dec 26.

Laboratório de Toxicologia Analítica e de Sistemas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, SP, Brazil.

The objective of this short paper is to call upon the scientific community to channel its attention to the duty and heedfulness of social justice issues. While recognized for decades the impact of social injustice on public health and its disproportionate effects on poorer communities, little has been done to systematically address it. Here, we provide several examples pertinent to the health outcomes associated with social injustice and call upon the scientific community to attend to the issue and antagonize those who attempt to subvert science and its role in ensuring social justice in health.
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http://dx.doi.org/10.1016/j.envres.2020.110675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946715PMC
March 2021

Improved strategies to counter the COVID-19 pandemic: Lockdowns vs. primary and community healthcare.

Toxicol Rep 2021 3;8:1-9. Epub 2020 Dec 3.

Department of Analytical Toxicology, Pharmaceutical Chemistry and Pharmacognosy, Sechenov University, 119991, Moscow, Russia.

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.
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http://dx.doi.org/10.1016/j.toxrep.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713637PMC
December 2020

Curcumin Formulations and Trials: What's New in Neurological Diseases.

Molecules 2020 Nov 18;25(22). Epub 2020 Nov 18.

Genomic and Post Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy.

Curcumin's pharmacological properties and its possible benefits for neurological diseases and dementia have been much debated. In vitro experiments show that curcumin modulates several key physiological pathways of importance for neurology. However, in vivo studies have not always matched expectations. Thus, improved formulations of curcumin are emerging as powerful tools in overcoming the bioavailability and stability limitations of curcumin. New studies in animal models and recent double-blinded, placebo-controlled clinical trials using some of these new formulations are finally beginning to show that curcumin could be used for the treatment of cognitive decline. Ultimately, this work could ease the burden caused by a group of diseases that are becoming a global emergency because of the unprecedented growth in the number of people aged 65 and over worldwide. In this review, we discuss curcumin's main mechanisms of action and also data from in vivo experiments on the effects of curcumin on cognitive decline.
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http://dx.doi.org/10.3390/molecules25225389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698610PMC
November 2020

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases.

Food Chem Toxicol 2020 Dec 16;146:111809. Epub 2020 Oct 16.

Yaroslavl State University, Yaroslavl, Russia.

Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for COronaVIrus Disease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19.
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http://dx.doi.org/10.1016/j.fct.2020.111809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563920PMC
December 2020

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19.

Food Chem Toxicol 2020 Dec 30;146:111769. Epub 2020 Sep 30.

Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania. Electronic address:

Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection can also affect the gastrointestinal tract, liver and pancreatic functions, leading to gastrointestinal symptoms. Moreover, SARS-CoV-2 can cause central and peripheral neurological manifestations, affect the cardiovascular system and promote renal dysfunction. Epidemiological data have indicated that cancer patients are at a higher risk of contracting the SARS-CoV-2 virus. Considering the multitude of clinical symptoms of COVID-19, the objective of the present review was to summarize their pathophysiology in previously healthy patients, as well as in those with comorbidities. The present review summarizes the current, though admittedly fluid knowledge on the pathophysiology and symptoms of COVID-19 infection. Although unclear issues still remain, the present study contributes to a more complete understanding of the disease, and may drive the direction of new research. The recognition of the severity of the clinical symptoms of COVID-19 is crucial for the specific therapeutic management of affected patients.
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http://dx.doi.org/10.1016/j.fct.2020.111769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833750PMC
December 2020

Health risk assessment of aflatoxin M1 in infant formula milk in IR Iran.

Food Chem Toxicol 2020 Aug 28;142:111455. Epub 2020 May 28.

Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece.

In this study, two accurate, precise, selective and sensitive methods were developed for determining aflatoxin M1 (AFM1) in infant formula milk using immunoaffinity column clean-up followed by high performance liquid chromatography (HPLC) with fluorescence detection. The validated methods were used for determination of AFM1 in 29 samples of 6 different infant formula milk brands and the risk of AFM1 in infants aged zero to 6 months old was assessed using cancer risk, Margin of Exposure (MOE) and Hazard Index (HI). Only one sample (3.4%) was contaminated with AFM1. Although the results showed that MOE values for the mean and median exposure to AFM1 was <10,000 in infants, the additional cancer risk due to mean and median exposure to AFM1 in infant <6 months were 0.00010 and 0.00012 additional cases per year per 10 individuals, respectively, which indicates no health concern. In addition, HI values for the mean and median exposure to AFM1 for infants were quite below one which indicates no health concern. To the best of our knowledge, this is the first report on risk assessment of AFM1 in infant formula milk consumed by Iranian infants <6 months old, presenting a low risk for the evaluated groups.
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http://dx.doi.org/10.1016/j.fct.2020.111455DOI Listing
August 2020

Biochemical adaptation of wild and cultivated soybean against toxicity of lead salts.

Environ Toxicol Pharmacol 2020 Oct 27;79:103429. Epub 2020 May 27.

Education and Scientific Center of Nanotechnology, Far Eastern Federal University, Vladivostok, 690950, Russia. Electronic address:

Agricultural production is becoming increasingly dependent on the environmental factors that alter soil properties, plant productivity, and product quality. Environment pollution caused by heavy metals because of human activities are among the most dangerous pollutants on the biosphere. Here, we have studied the biochemical adaptation of wild and cultivated soybeans to the simulated effects of lead nitrate and lead acetate. Lead in the form of acetate had a relevant toxic effect, as evidenced by a significant increase in the concentration of malonic dialdehyde in the treated samples relative to control samples. Catalase and peroxidase, possibly performing a signaling function, are involved in the adaptation to the toxicity of Pb salts. The studied Pb salts showed a predominant stimulating effect on the specific activity of acid phosphatases in cultivated soybean, while the ribonuclease activity changed in both Glycine species. Moreover, in wild soybean, it was mostly suppressive, except for the first day. We found that the electrophoretic spectra of acid phosphatases of soybean seedlings was highly stabile, while that of ribonucleases varied depending on the salt. On the seventh day of exposure, lead nitrate caused a decrease in the specific activity of the studied hydrolases of seedlings of cultivated and wild soybeans. A change in the number or electrophoretic mobility of multiple forms of enzymes during treatment with Pb salts was revealed, which indicates the adaptation of the plants at the molecular genetic level. These results imply that the observed enzymes can be used as sensitive indicators for predicting the effects of heavy metals on soybean.
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http://dx.doi.org/10.1016/j.etap.2020.103429DOI Listing
October 2020

Benomyl, a benzimidazole fungicide, induces oxidative stress and apoptosis in neural cells.

Toxicol Rep 2020 11;7:501-509. Epub 2020 Apr 11.

Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500, Larissa, Greece.

Fungicides are used in the agricultural sector against the harmful action of fungi, however they are potential toxic agents for the environment and the living organisms. Benomyl is a widely encountered benzimidazole fungicide that exerts its toxicity via inhibiting microtubule formation in the nervous system and the male reproductive and endocrine systems, whilst it is a known teratogen. Since toxic effects of benomyl and its molecular mechanisms are not fully understood, we aimed to detect its neurotoxic potential via evaluating cytotoxicity, oxidative stress and apoptosis in SH-SY5Y cell line. The cells were incubated with benomyl in a concentration range between 1 and 6 μM for 24 h. Our results indicated a concentration-dependent enhancement of reactive oxygen species measured through flow cytometry and DNA damage evaluated via the comet assay. Additionally, it induced apoptosis in all tested concentrations. According to the findings of the present study, benomyl is a xenobiotic, which it appears to exert its toxic action via a redox-related mechanism that, finally, induces cell apoptosis and death. We believe that this study will offer further insight in the toxicity mechanism of benomyl, although further studies are recommended in order to elucidate these mechanisms in the molecular level.
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http://dx.doi.org/10.1016/j.toxrep.2020.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175046PMC
April 2020

Carbon monoxide poisoning.

Toxicol Rep 2020 20;7:169-173. Epub 2020 Jan 20.

Department of Toxicology & Forensic Sciences, Medical School, University of Crete, Voutes Campus, Heraklion, 71003, Greece.

Carbon monoxide (CO) is the leading cause of poisoning deaths in many countries, including Japan. Annually, CO poisoning claims about 2000-5000 lives in Japan, which is over half of the total number of poisoning deaths. This paper discusses the physicochemical properties of CO and the toxicological evaluation of CO poisoning.
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http://dx.doi.org/10.1016/j.toxrep.2020.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992844PMC
January 2020

Adverse health effects of 5G mobile networking technology under real-life conditions.

Toxicol Lett 2020 May 25;323:35-40. Epub 2020 Jan 25.

Laboratory of Toxicology, Medical School, University of Crete, Voutes, 71409 Heraklion, Crete, Greece; Department of Analytical, Toxicology, Pharmaceutical Chemistry and Pharmacognosy, Sechenov University, 119991 Moscow, Russia. Electronic address:

This article identifies adverse effects of non-ionizing non-visible radiation (hereafter called wireless radiation) reported in the premier biomedical literature. It emphasizes that most of the laboratory experiments conducted to date are not designed to identify the more severe adverse effects reflective of the real-life operating environment in which wireless radiation systems operate. Many experiments do not include pulsing and modulation of the carrier signal. The vast majority do not account for synergistic adverse effects of other toxic stimuli (such as chemical and biological) acting in concert with the wireless radiation. This article also presents evidence that the nascent 5G mobile networking technology will affect not only the skin and eyes, as commonly believed, but will have adverse systemic effects as well.
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http://dx.doi.org/10.1016/j.toxlet.2020.01.020DOI Listing
May 2020

A review of the alleged health hazards of monosodium glutamate.

Compr Rev Food Sci Food Saf 2019 Jul 8;18(4):1111-1134. Epub 2019 May 8.

Faculty of Pharmacy, "Carol Davila" Univ. of Medicine and Pharmacy, Traian Vuia 6, Bucharest, 020956, Romania.

Monosodium glutamate (MSG) is an umami substance widely used as flavor enhancer. Although it is generally recognized as being safe by food safety regulatory agencies, several studies have questioned its long-term safety. The purpose of this review was to survey the available literature on preclinical studies and clinical trials regarding the alleged adverse effects of MSG. Here, we aim to provide a comprehensive overview of the reported possible risks that may potentially arise following chronic exposure. Furthermore, we intend to critically evaluate the relevance of this data for dietary human intake. Preclinical studies have associated MSG administration with cardiotoxicity, hepatotoxicity, neurotoxicity, low-grade inflammation, metabolic disarray and premalignant alterations, along with behavioral changes. Moreover, links between MSG consumption and tumorigenesis, increased oxidative stress and apoptosis in thymocytes, as well as genotoxic effects in lymphocytes have been reported. However, in reviewing the available literature, we detected several methodological flaws, which led us to conclude that these studies have limited relevance for extrapolation to dietary human intakes of MSG risk exposure. Clinical trials have focused mainly on the effects of MSG on food intake and energy expenditure. Besides its well-known impact on food palatability, MSG enhances salivary secretion and interferes with carbohydrate metabolism, while the impact on satiety and post-meal recovery of hunger varied in relation to meal composition. Reports on MSG hypersensitivity, also known as 'Chinese restaurant syndrome', or links of its use to increased pain sensitivity and atopic dermatitis were found to have little supporting evidence. Based on the available literature, we conclude that further clinical and epidemiological studies are needed, with an appropriate design, accounting for both added and naturally occurring dietary MSG. Critical analysis of existing literature, establishes that many of the reported negative health effects of MSG have little relevance for chronic human exposure and are poorly informative as they are based on excessive dosing that does not meet with levels normally consumed in food products.
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http://dx.doi.org/10.1111/1541-4337.12448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952072PMC
July 2019

Sildenafil and tadalafil reduce the risk of contrast-induced nephropathy by modulating the oxidant/antioxidant balance in a murine model.

Food Chem Toxicol 2020 Jan 9;135:111038. Epub 2019 Dec 9.

Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania. Electronic address:

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.
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http://dx.doi.org/10.1016/j.fct.2019.111038DOI Listing
January 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

Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a Southeastern European Caucasian Cluster Headache Population.

J Mol Neurosci 2020 Mar 25;70(3):467-474. Epub 2019 Nov 25.

Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece.

Studies point to an increased hereditary risk of cluster headache. HCRTR2 gene rs2653349 and ADH4 gene rs1800759 polymorphisms have been associated with cluster headache susceptibility. Also, GNB3 rs5443 polymorphism, associated with increased signal transduction via GPCRs, seems to influence triptan treatment response. DNA from 114 cluster headache patients and 570 non-related controls, representing a general Southeastern European Caucasian (SEC) population, was extracted from buccal swabs and genotyped using real-time PCR. Gene distribution for the rs2653349 was GG = 79.8%, GA = 18.4%, and AA = 1.8% for patients and GG = 79.1%, GA = 19.1%, and AA = 1.8% for controls. The frequency of the mutated A allele was 11.0% for patients and 11.3% for controls. The frequencies for rs5443 were CC = 44.7%, CT = 44.7%, and TT = 10.5% for patients and CC = 43.9%, CT = 42.6%, and TT = 13.5% for controls. The frequency of the mutated T allele was 32.9% for patients and 34.8% for controls. A 2.7-fold more frequent appearance of the mutated T allele was observed in patients with better triptan treatment response, although not statistically significant. For rs1800759, the frequencies were CC = 36.0%, CA = 43.0%, and AA = 21.0% for patients and CC = 34.0%, CA = 50.2%, and AA = 15.8% for controls. The frequency of the mutated A allele was 42.5% and 40.9% for patients and controls, respectively. The mutated T allele of GNB3 rs5443 polymorphism was more prevalent in patients with better triptan treatment response, indicating a possible trend of association between this polymorphism and triptan treatment response in SEC population. According to our observation, no association of HCRTR2 rs2653349 and ADH4 rs1800759 polymorphisms and cluster headache in SEC population could be documented.
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http://dx.doi.org/10.1007/s12031-019-01439-0DOI Listing
March 2020

Transgenic crops for the agricultural improvement in Pakistan: a perspective of environmental stresses and the current status of genetically modified crops.

GM Crops Food 2020 3;11(1):1-29. Epub 2019 Nov 3.

Center of Agricultural Biochemistry and Biotechnology, University of Agriculture, Faisalabad, Pakistan.

Transgenic technologies have emerged as a powerful tool for crop improvement in terms of yield, quality, and quantity in many countries of the world. However, concerns also exist about the possible risks involved in transgenic crop cultivation. In this review, literature is analyzed to gauge the real intensity of the issues caused by environmental stresses in Pakistan. In addition, the research work on genetically modified organisms (GMOs) development and their performance is analyzed to serve as a guide for the scientists to help them select useful genes for crop transformation in Pakistan. The funding of GMOs research in Pakistan shows that it does not follow the global trend. We also present socio-economic impact of GM crops and political dimensions in the seed sector and the policies of the government. We envisage that this review provides guidelines for public and private sectors as well as the policy makers in Pakistan and in other countries that face similar environmental threats posed by the changing climate.
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http://dx.doi.org/10.1080/21645698.2019.1680078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158921PMC
February 2020

Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements.

Cells 2019 10 14;8(10). Epub 2019 Oct 14.

I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia.

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients' prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients' samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.
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http://dx.doi.org/10.3390/cells8101251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829588PMC
October 2019

Study Protocol of European Regulatory Science on Tobacco (EUREST-PLUS): Policy implementation to reduce lung disease.

Tob Induc Dis 2018 21;16:A2. Epub 2018 Aug 21.

University of Waterloo (UW), Waterloo, Canada.

Efforts to mitigate the devastation of tobacco-attributable morbidity and mortality in the European Union (EU) are founded on its newly adopted Tobacco Products Directive (TPD) along with the first-ever health treaty, the WHO Framework Convention on Tobacco Control (FCTC). The aim of this Horizon 2020 Project entitled is to monitor and evaluate the impact of the implementation of the TPD across the EU, within the context of WHO FCTC ratification. To address this aim, EUREST-PLUS consists of four objectives: 1) To create a cohort study of 6000 adult smokers in six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) within a pre-TID vs post-TPD implementation study design; 2) To conduct secondary dataset analyses of the Special Eurobarometer on Tobacco Survey (SETS); 3) To document changes in e-cigarette product parameters (technical design, labelling/packaging and chemical composition) pre-TID vs post-TPD; and 4) To enhance innovative joint research collaborations on chronic non-communicable diseases. Through this methodological approach, EUREST-PLUS is designed to generate strong inferences about the effectiveness of tobacco control policies, as well as to elucidate the mechanisms and factors by which policy implementation translates to population impact. Findings from EUREST-PLUS have potential global implications for the implementation of innovative tobacco control policies and its impact on the prevention of lung diseases.
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http://dx.doi.org/10.18332/tid/93305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659480PMC
August 2018

A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse.

J Clin Med 2019 Aug 23;8(9). Epub 2019 Aug 23.

Department of Immunology, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania.

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming.
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http://dx.doi.org/10.3390/jcm8091295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780697PMC
August 2019

Soil copper uptake by land snails: A semi-field experiment with juvenile Cantareus aspersus snails.

Environ Toxicol Pharmacol 2019 Nov 16;72:103243. Epub 2019 Aug 16.

Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq 2, 300041, Timisoara, Romania. Electronic address:

There is currently limited scientific evidence linking soil copper and land snails, although these invertebrates are important players in terrestrial ecosystems. In the present study, Cantareus aspersus juveniles, were exposed in two successive phases of 30 days each, to soil spiked with increasing concentrations of copper sulfate. Copper concentrated preferentially and in a dose-dependent manner in the hepatopancreas. In the case of specimens previously exposed to Cu-spiked soils, Cu retention kinetics were independent from the effects of a new exposure event. There was no effect on shell growth, but significant mortality was observed at 60 days. The no observed effect concentration and the lowest observed effect concentration for mortality in snails, were ˜ 41 and 54 mg, respectively, per grams dry weight in the hepatopancreas. The results demonstrate, for the first time, that terrestrial gastropods can accumulate soil Cu autonomously from dietary uptake.
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http://dx.doi.org/10.1016/j.etap.2019.103243DOI Listing
November 2019

Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics.

Cells 2019 08 9;8(8). Epub 2019 Aug 9.

Centre of Toxicology Science and Research, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece.

Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.
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http://dx.doi.org/10.3390/cells8080863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721640PMC
August 2019
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