Papers by George P Chrousos
Deleted Journal, May 10, 2024
Conflicts and wars, particularly prevalent in regions such as Africa, the Middle East and Asia, h... more Conflicts and wars, particularly prevalent in regions such as Africa, the Middle East and Asia, have profound and multifaceted effects on individuals, spanning socioeconomic, medical and psychological realms. The present review delves into the intricate interplay between genetics, epigenetics and the experiences of individuals, particularly children, in conflict zones. Genetics, the study of inherited traits, and epigenetics, the study of how environmental factors influence gene expression, jointly shape the development and response to trauma of an individual. While traditionally, genes were considered the sole determinants of traits, epigenetic modifications reveal the significant role of environmental factors. Children in war zones are particularly vulnerable, suffering from a myriad of physical and psychological traumas, including post-traumatic stress disorder and depression. Moreover, exposure to violence during critical developmental periods can have transgenerational effects, affecting the mental and physical health of subsequent generations. Recent research highlights epigenetic changes in individuals affected by historical traumas, such as the Holocaust, demonstrating how parental trauma can influence offspring. Interventions targeting epigenetic mechanisms show promise in mitigating the effects of trauma. Narrative exposure therapy and other psychological interventions have been shown to induce epigenetic changes associated with memory and trauma processing, offering hope for affected individuals. Additionally, environmental influences during critical periods, such as famine during adolescence, have been linked to long-term health outcomes, including the risk of developing colorectal cancer. Herein, the intricate interplay between genetics, epigenetics and environmental factors in shaping individual responses to trauma is underscore. Further research on a larger scale is warranted to validate and expand upon these findings, offering insight into potential avenues for intervention and support for individuals affected by conflict-related trauma. Contents 1. Introduction 2. Genetics and epigenetics of the war child 3. Conclusion
Frontiers in Psychology, Jul 20, 2020
Children
This research outlines the initial validation of a new instrument to quantify academic stress, th... more This research outlines the initial validation of a new instrument to quantify academic stress, the Educational Stress Scale for Adolescents (ESSA). A total of 399 students (61.9% females, 38.1% males), with a mean age of 16.3 years, participated in the research protocol. Cronbach’s α for the total 16-item ESSA scale was 0.878, suggesting good reliability. Cronbach’s α for each one of the five components were statistically positively significant. The Greek version of the Educational Stress Scale for Adolescents (ESSA) can be utilized as a valid tool to measure the perceived educational stress in adolescents.
Molecules
The poly(A) tail at the 3′ end of mRNAs determines their stability, translational efficiency, and... more The poly(A) tail at the 3′ end of mRNAs determines their stability, translational efficiency, and fate. The shortening of the poly(A) tail, and its efficient removal, triggers the degradation of mRNAs, thus, regulating gene expression. The process is catalyzed by a family of enzymes, known as deadenylases. As the dysregulation of gene expression is a hallmark of cancer, understanding the role of deadenylases has gained additional interest. Herein, the genetic association network shows that CNOT6 and CNOT7 are the most prevalent and most interconnected nodes in the equilibrated diagram. Subsequent silencing and transcriptomic analysis identifies transcripts possibly regulated by specific deadenylases. Furthermore, several gene ontologies are enriched by common deregulated genes. Given the potential concerted action and overlapping functions of deadenylases, we examined the effect of silencing a deadenylase on the remaining ones. Our results suggest that specific deadenylases target u...
Nutrients, 2021
Self-efficacy is perhaps the most important parameter associated with behavioral changes. The mai... more Self-efficacy is perhaps the most important parameter associated with behavioral changes. The main aim of this study was to provide insight into the diet and exercise self-efficacy of Greek adolescents and how they could be modified via a multilevel multicomponent school-based lifestyle intervention. Secondary aims were to study the associations of students’ dietary and exercise self-efficacy indices with their anthropometric and sociodemographic parameters. A representative sample of the adolescent population in Attica, consisting of 1610 adolescents aged 12–17 years, recruited from 23 public high schools in three municipalities of the Attica area in Greece, received a three-component lifestyle educational intervention for health promotion and underwent screening for characteristics of metabolic syndrome with the use of portable telemedicine. All assessments and anthropometric measurements were performed at baseline and after the 6-month intervention. Anthropometric measurements in...
Biosensors, 2021
The availability of antigen tests for SARS-CoV-2 represents a major step for the mass surveillanc... more The availability of antigen tests for SARS-CoV-2 represents a major step for the mass surveillance of the incidence of infection, especially regarding COVID-19 asymptomatic and/or early-stage patients. Recently, we reported the development of a Bioelectric Recognition Assay-based biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus in just three minutes, with high sensitivity and selectivity. The working principle was established by measuring the change of the electric potential of membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody after attachment of the respective viral protein. In the present study, we applied the novel biosensor to patient-derived nasopharyngeal samples in a clinical set-up, with absolutely no sample pretreatment. More importantly, membrane-engineered cells were pre-immobilized in a proprietary biomatrix, thus enabling their long-term preservation prior to use as well as significantly increa...
International Journal of Epigenetics, 2020
Molecular Medicine Reports, 2020
Studies on extracellular vesicles have increased in recent years. The multi-dimensional nature of... more Studies on extracellular vesicles have increased in recent years. The multi-dimensional nature of their roles in cellular homeostasis, cell-to-cell and tissue-to-tissue communication at the level of the organism, as well as their actions on the holobiome (intra-/interspecies interaction), have garnered the interest of a large number of researchers. Exosomes are one of the most researched classes of extracellular vesicles because they are carriers of targeted protein and DNA/RNA loads. Their multi-functional cargo have been indicated to regulate a vast number of biological pathways in target cells. However, the mechanisms governing these interactions have not yet been fully determined. Endocrinology, by definition, focuses on homeostatic, and cell-to-cell and tissue-to-tissue communication mechanisms. Therefore exosomes should be included in this research topic. Exosomes have previously been associated with a number of endocrine disorders, including obesity, type 2 diabetes mellitus, disorders of the reproductive system and cancer. Furthermore, their biogenesis, composition and function have been associated with viruses, an entirely different domain of life. The profound roles of exosomes in homeostasis, stress and several pathological conditions, in conjunction with their selective and cell-specific composition/function, allude to their use as promising circulating clinical biomarkers of systemic stress and specific pathologic states, and as biocompatible vehicles of therapeutic cargo. The current review provides information on exosomes and discusses their endocrine implications. 1. Introduction 2. An in-depth view of exosomes 3. Cell-to-cell interactions and the microenvironment 4. Biological processes 5. Disorders of the endocrine system and exosomes 6. Exosome-based personalized medical applications 7. Conclusion
Nutrients, 2019
Background: Gaps remain on the safety of egg intake on cardiovascular health, setting the study’s... more Background: Gaps remain on the safety of egg intake on cardiovascular health, setting the study’s aim to investigate the association between quantity and frequency of egg consumption, with established dyslipidemia. Methods: Study participants (N = 3558, 40.3% males) included individuals from the Hellenic National and Nutrition Health Survey (HNNHS), of national representation. Quantity and frequency of egg consumption was determined. Minimally adjusted, multivariable logistic and linear analysis were used to assess egg consumption and dyslipidemia. Results: The more frequent egg consumption compared to no or rare egg consumption significantly decreased the odds of dyslipidemia in the minimally adjusted (Odds Ratio (OR) for frequency: 0.83; 95% Confidence Interval (CI): 0.752, 0.904; OR for quantified frequency: 0.87; 95% CI: 0.796, 0.963) and the fully adjusted models (OR for frequency: 0.80; 95% CI: 0.718, 0.887; OR for quantified frequency: 0.85; 95%CI: 0.759, 0.945). Level of ser...
Endocrine connections, 2018
Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of β cells of the endocri... more Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of β cells of the endocrine pancreas. Pathogenesis of T1DM is different from that of type 2 diabetes mellitus, where both insulin resistance and reduced secretion of insulin by the β cells play a synergistic role. We will present genetic, environmental and immunologic factors that destroy β cells of the endocrine pancreas and lead to insulin deficiency. The process of autoimmune destruction takes place in genetically susceptible individuals under the triggering effect of one or more environmental factors and usually progresses over a period of many months to years, during which period patients are asymptomatic and euglycemic, but positive for relevant autoantibodies. Symptomatic hyperglycemia and frank diabetes occur after a long latency period, which reflects the large percentage of β cells that need to be destroyed before overt diabetes become evident.
Journal of molecular biochemistry, 2017
Frailty is a natural state of physical, cognitive and mental decline that is expected in the elde... more Frailty is a natural state of physical, cognitive and mental decline that is expected in the elderly. The role of inflammation in the pathogenesis of frailty has been hypothesized, and so far many studies have been performed in order to understand the mechanism of action underlying this association. Recent studies support this hypothesis and show a clear association between inflammation, frailty, and age-related disease. Chronic inflammation is key pathophysiologic process that contributes to the frailty directly and indirectly through other intermediate physiologic systems, such as the musculoskeletal, endocrine, and hematologic systems. The complex multifactorial etiologies of frailty also include obesity and other age-related specific diseases. Herein, we investigate the link between chronic inflammation and frailty of the older people. In particular, we present an up-to-date review of the role of cytokines, interleukins, cardiovascular abnormalities, chronic high blood pressure,...
PharmacoEconomics - Open, 2017
Background The Migraine Disability Assessment (MIDAS) Questionnaire is a reliable and valid instr... more Background The Migraine Disability Assessment (MIDAS) Questionnaire is a reliable and valid instrument for migraine-related disability. Such a tool is needed to quantify migraine-related disability in the Greek population. Objective This validation study aims to assess the test-retest reliability, internal consistency, item discriminant and convergent validity of the Greek translation of the MIDAS. Methods Adults diagnosed with migraine completed the MIDAS Questionnaire on two occasions 3 weeks apart to assess reliability, and completed the RAND-36 to assess validity. Results Participants (n = 152) had a median MIDAS score of 24 and mostly severe disability (58% were grade IV). The testretest reliability analysis (N = 59) revealed excellent reliability for the total score. Internal consistency was a = 0.71 for initial and a = 0.82 for retest completion. For item discriminant validity, the correlations between each question and the total score were significant, with high correlations for questions 2-5 (range 0.67 B r B 0.79; p \ 0.01). For convergent validity, there was significant negative correlation between the total score and all RAND-36 subscales except for 'emotional wellbeing'. The negative correlation indicates that patients with a lower degree of disability according to their MIDAS score tended to have better wellbeing. Psychometric properties are comparable with those of other published validation studies of the MIDAS and the original. Findings on question 1 show that missing work/school days may be closely related with increased affect issues. The Greek version of the MIDAS Questionnaire has good reliability and validity. This study allowed for cross-cultural comparability of research findings. The Greek version of the Migraine Disability Assessment (MIDAS) Questionnaire has good internal consistency, item-discriminant and convergent validity and test-retest reliability. It can be used in research as well as for stratified migraine care in clinical settings. Findings show that missing work or school days may be more closely related with increased affect issues compared with physical limitations imposed by migraine.
International Journal of Molecular Sciences, 2017
γH2AX has emerged in the last 20 years as a central player in the DDR (DNA damage response), with... more γH2AX has emerged in the last 20 years as a central player in the DDR (DNA damage response), with specificity for DSBs (double-strand breaks). Upon the generation of DSBs, γ-phosphorylation extends along megabase-long domains in chromatin, both sides of the damage. The significance of this mechanism is of great importance; it depicts a biological amplification mechanism where one DSB induces the γ-phosphorylation of thousands of H2AX molecules along megabaselong domains of chromatin, that are adjusted to the sites of DSBs. A sequential recruitment of signal transduction factors that interact to each other and become activated to further amplify the signal that will travel to the cytoplasm take place on the γ-phosphorylated chromatin. γ-phosphorylation is an early event in the DSB damage response, induced in all phases of the cell cycle, and participates in both DSB repair pathways, the HR (homologous recombination) and NHEJ (non-homologous end joining). Today, numerous studies support the notion that γH2AX functions as a guardian of the genome by preventing misrepaired DSB that increase the mutation load of the cells and may further lead to genome instability and carcinogenesis.
Physical therapy, Jan 4, 2015
Only a few studies have been conducted in order to create norms of the Alberta Infant Motor Scale... more Only a few studies have been conducted in order to create norms of the Alberta Infant Motor Scale (AIMS) for the assessment of gross motor development of preterm (PT) infants; AIMS performance of PT infants was compared with that of the Canadian norms of full-term (FT) infants, but not with FT infants of the same nationality. Moreover, the possible impact of prematurity-related morbidity factors on AIMS performance is unknown. To evaluate AIMS trajectory in a large population of Greek PT infants and create norms; to compare it with AIMS trajectory of Greek FT infants; and to examine the possible influence of neonatal morbidity on AIMS scores in the PT sample. Cross-sectional study METHODS: Mean AIMS scores were compared, per month (1-19), between 403 PT infants (≤32 weeks) at corrected for prematurity age and 1038 FT infants. In PT infants, association of AIMS scores with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) of grade ≤III, bronchopulmonary dysplasia...
European Respiratory Journal, 2015
Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic–pitui... more Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic–pituitary–adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use.72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment.In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls.These results suggest that OSA in nonobese men a...
Drugs acting on homeostasis: challenging cancer cell adaptation
Expert Review of Anticancer Therapy, 2015
Cancer treatment aims to exploit properties that define malignant cells. In recent years, it has ... more Cancer treatment aims to exploit properties that define malignant cells. In recent years, it has become apparent that malignant cells often survive cancer treatment and ensuing cell stress by switching on auxiliary turnover pathways, changing cellular metabolism and, concomitantly, the gene expression profile. The changed profile impacts the material exchange of cancer cells with affected tissues. Herein, we show that pathways of proteostasis and energy generation regulate common transcription factors. Namely, when one pathway of intracellular turnover is blocked, it triggers alternative turnover mechanisms, which induce transcription factor proteins that control expression of cytokines and regulators of apoptosis, cell division, differentiation, metabolism, and response to hormones. We focus on several alternative turnover mechanisms that can be blocked by drugs already used in clinical practice for the treatment of other non-cancer related diseases. We also discuss paradigms on the challenges posed by cancer cell adaptation mechanisms.
Cytokine & growth factor reviews, Jan 20, 2015
Recently it was discovered that a transient activation of transcription factor NF-κB can give cel... more Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells.
BioMed research international, 2013
The aim of the present study was to investigate the associations of iron depletion (ID) with mens... more The aim of the present study was to investigate the associations of iron depletion (ID) with menstrual blood losses, lifestyle, and dietary habits, in pubertal girls. The study sample comprised 1222 girls aged 9-13 years old. Biochemical, anthropometrical, dietary, clinical, and physical activity data were collected. Out of 274 adolescent girls with menses, 33.5% were found to be iron depleted (defined as serum ferritin < 12 μg/L) compared to 15.9% out of 948 girls without menses. Iron-depleted girls without menses were found to have lower consumption of poultry (P = 0.017) and higher consumption of fruits (P = 0.044) and fast food (P = 0.041) compared to their peers having normal iron status. Multivariate logistic regression analysis showed that girls with menses were 2.57 (95% CI: 1.37, 4.81) times more likely of being iron depleted compared to girls with no menses. Iron depletion was found to be associated with high calcium intake, high consumption of fast foods, and low consu...
Virology, 1998
Yeast two-hybrid selection of proteins interacting with human immunodeficiency virus type 1 Vpr i... more Yeast two-hybrid selection of proteins interacting with human immunodeficiency virus type 1 Vpr identified HHR23A, a human homologue of the yeast DNA repair protein RAD23, as a specific interactor. A small 57-amino-acid C-terminal portion of HHR23A was sufficient for Vpr interaction. When introduced into human cells by transfection, full-length HHR23A or its C-terminal fragments were able to alleviate Vpr-induced cell cycle arrest, suggesting that HHR23A may participate in the pathway leading to G2 arrest by Vpr. We have also examined the effects of HHR23 on the recently identified transcription coactivator function of Vpr. The two Vpr functions are independent, since we have identified mutants lacking either the cell cycle arrest or the coactivator function. Our analysis showed that excess of HHR23A does not affect the coactivator function of Vpr, while it affects the cell cycle arresting function. Therefore, a simple sequestering model for Vpr in the presence of excess HHR23A is not supported. We propose that the interaction of HHR23A with Vpr may affect specifically pathways leading to cell cycle regulation.
Trends in Endocrinology & Metabolism, 2007
Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects women of reproductive age. PCO... more Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects women of reproductive age. PCOS shares components with the metabolic syndrome and has broad health implications. Lipid abnormalities, including elevated low-density lipoprotein (LDL), triglyceride levels and decreased high-density lipoprotein (HDL), are often found in women with PCOS. It is clear that obesity, insulin resistance and hyperandrogenism coexist in PCOS, and have independent and interactive effects on dyslipidemia, although the mechanisms of these interactions remain elusive. Here, we review the types and pathophysiology of dyslipidemia associated with PCOS and its related conditions. Review
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Papers by George P Chrousos