Liquid-liquid phase separation (LLPS) has been recently suggested as a new potential mechanism underpinning various organizational aspects of the cell, from the formation of sub-cellular, biomolecule enrichments to the assembly of organelles. In eukaryotes, DNA replication follows a strict temporal and spatial program that is majorly affected by the chromatin structure, the nuclear organization and the availability of limiting initiation factors; however the regulatory mechanisms driving the process have not been fully elucidated. Original data published lately revealed for the first time that the components of the pre-replicative complex, ORC, Cdc6 and Cdt1, are able to phase separate indicating a possible connection between LLPS and DNA replication. Here, we critically present these preliminary data and propose mechanistic models that could support this regulatory link and lead to new future research directions.
Objective To examine the validity and the reliability of a novel measurement tool, the Newly Diagnosed Breast Cancer Stress Scale (NDBCSS) in the Greek population. The tool aimed to assess distress in patients recently diagnosed with breast cancer. Methods We performed a principal component analysis (PCA) of the 17 items of the scale. Results The PCA resulted in 4 factors: 1. Personal life, 2. Procedural issues, 3. Facing challenges and 4. Psychological load. All subscales showed satisfactory internal consistency and variance, relative to theoretical score ranges. Subscale scores and total score were significantly correlated with perceived stress and hospital anxiety and depression scale, implying good criterion validity. Associations with social, demographic and disease related information were also found. Conclusions The NDBCSS resulted in acceptable reliability and good validity, and was considered as a valuable tool for health-care workers and oncologists to measure psychological distress in early stage of breast cancer.
BACKGROUND:The aim of this study was to evaluate the effect of a novel cognitive-behavioral stress management intervention, termed "Pythagorean Self-Awareness Intervention" (PSAI). Materials and Methods: The PSAI was applied to a community sample for eight weeks. Measurements included demographic characteristics, daily habits, sleep quality, fatigue, perceived stress levels and depressive symptoms. Cognitive function was measured by the Symbol Digits Modality Test (SDMT), the California Verbal Learning Test (CVLT) and the Brief Visuospatial Memory Test-Revised (BVMT-R). RESULTS:The high-compliance group showed statistically significant differences in healthy lifestyle and personal control choices (HLPCQ; p=0.006), sleep quality (PSQI; p=0.007), self-regulation eating behavior (SREBQ; p=0.009), perceived stress (PSS; p=0.001) and depressive symptoms (p=0.003). Conclusions: Frequent practice of the PSAI had a positive effect on the psychological, lifestyle, and cognitive measures of the community sample. Larger studies are needed to establish the PSAI as an effective stress management method.
Background Emotional eating is the tendency to regulate negative emotions (such as stress, depression and anxiety) through increased or unhealthy food intake. Emotion management, such as stress management could be an appropriate approach to prevent or control maladaptive eating behavior among children. Materials and methods This is a controlled pragmatic trial, testing the effects of Pythagorean Self Awareness Intervention (PSAI), a cognitive stress management program in a primary school setting. The eligibility criterion was being a 4th grade active pupil. Participants were randomly assigned to either the intervention group (n = 23) or the control group (n = 22). Self-report measures were used for the evaluation of various variables at the beginning and the end of the 8-week monitoring period. Descriptive and inferential statistic methods were used for the statistical analysis. Results At the end of the 8-week period pupils in the intervention group experienced statistically significant reduction in stress (SIC, p < 0.001), anxiety (STAIC-trait anxiety, p = 0.019, STAIC-state anxiety, p = 0.006), guilt (p < 0.001) and emotional eating (EES-C, p < 0.001) and an increase in Mediterranean diet quality (KIDMED, p = 0.001) and pride (p < 0.001). No statistically significant differences between the two groups were recorded regarding depression symptoms (CDI, p = 0.551) and shame (p = 0.120). Conclusions PSAI had positive effects on a sample of primary school attendants' emotional eating and psychological state.
AimThe aim of this study is to compare and evaluate the sort-term benefits of the effects of an 8-week stress management techniques in information technology professionals.MethodsIn this parallel randomized controlled trial, participants were randomly assigned to either the stress management group (n=40; relaxation breathing, progressive muscle relaxation, guided imagery) or in the Pythagorean Self awareness group (n=41). Self-reported validated measures were used to evaluate perceived stress, health locus of control, anxiety and depression.ResultsAll groups were found with significantly better cognitive speed and verbal memory at the end of the follow-up. Taking into account the group by time interaction coefficients, PSAT was found significantly superior to standard SM with regards to depression, emotional intelligence, lifestyle and personal control and verbal memory suggesting that verbal memory improvement through time should be mostly attributed to PSAT. On the other hand, the cognitive speed improvement during follow-up should be attributed to both interventions.ConclusionsThese findings provide important insight into the role of stress management. Future studies should focus on randomized, controlled trials with larger samples and longer follow-up times.
AIM:The purpose of this study was to validate a Greek version of the Stress in Children (SiC) Questionnaire and assess its psychometric qualities in a Greek pediatric sample. MATERIALS AND METHODS:Healthy children aged 8-12 years, attending schools of various areas of Attica, the largest region in Greece, were eligible to participate in the study. Data were collected from May 2016 until June 2017, anonymously, though three self-reported questionnaires, a simple demographic questionnaire, the SiC Questionnaire and the State and Trait Anxiety in Children Questionnaire. RESULTS:Questionnaires were completed by 100 pupils (54 boys, 46 girls) aged (mean ± SD) 10.6 ± 1.26 years. A three-factor structure ("Distress", "Presence of well-being", and "Presence of social support") accounted for 41.33% of variance. Reliability Cronbach's alpha of "Distress", "Presence of well-being" and "Presence of social support" factors was equal to 0.75, 0.75 and 0.61, respectively. Regarding concurrent validity, positive correlations were found between "Distress" and both trait anxiety (rho=0.59, p<0.0001) and state anxiety (rho=0.61, p<0.0001). Correlations were also found between "Presence of Wellbeing" and age (rho=-0.24, p=0.019), state (rho=-0.36, p=0.006) and trait anxiety (rho=-0.45, p<0.0001). CONCLUSIONS:The Greek version of SiC Questionnaire demonstrated satisfactory psychometric properties (content validity, internal reliability) that support its use in Greek children.
AIM:Stress has been implicated in the pathogenesis of Hashimoto's thyroiditis (HT), nevertheless evidence is scarce regarding the effect of stress management on individuals suffering from HT. The purpose of this study was to evaluate the impact of an 8-week stress management intervention on the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies as well as thyroid-stimulating hormone (TSH) levels of women with HT. Secondary endpoints included the effect on the patients' lifestyle, body mass index (BMI), depression, anxiety and stress.METHODS:This was a two-arm parallel group (stress management intervention vs. standard care groups) randomized controlled study. Adult women with Hashimoto's thyroiditis, completed questionnaires on stress, anxiety, depression and lifestyle, at the beginning of the programme and 8 weeks later. Laboratory thyroid function tests (anti-TPO, anti-TG antibodies and TSH) were also measured at baseline and at the end of the study.RESULTS:A total of 60 women with HT, aged 25-76 years, participated in the study (30 patients in each group). After eight weeks, patients in the intervention group demonstrated statistically significant beneficial decrements in the rate change of anti-TG titers and the levels of stress, depression and anxiety as well as better lifestyle scores, compared to the control group.
AIM:In this study, we focused on the Greek validation of the Emotional Eating Scale for Children and Adolescents (EES-C).METHODS:Our sample consisted of 150 students in primary and secondary school settings from two different areas of Greece. Child Depression Inventory (CDI) and State and Trait Anxiety in Children (STAIC) were also used for validation purposes.RESULTS:The principal component factor analysis for construct validity generated three subscales: eating in response to anger/anxiety, feeling unsettled and de-pression. The EES-C tool was found with high internal reliability (Cronbach's Alpha 0.917).CONCLUSIONS:EES-C is a valid and reliable instrument to detect the emotional eating in children and adolescents in Greece.
Lactase deficiency can lead to significant symptoms in the pediatric population. To date, few studies have examined the prevalence of enzyme testing-based lactase and other disaccharidase deficiencies (DDs) in pediatric patients undergoing upper endoscopic evaluation. The primary objective of this study was to determine the prevalence of selective lactase and other DDs amongst a large cohort of pediatric patients with and without inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis) via a chart review of 739 patients who underwent esophago-gastro-dudenoscopy EGD between April 2010 and August 2016. We identified 560 pediatric patients (ages 1-18 years) who underwent mucosal enzyme testing at the time of their EGD. The overall rate of lactase deficiency (LD) was 39%. LD positively correlated with age (p=0.00017), but there was no significant difference between age matched IBD and non-IBD patients (45% vs. 42% p=0.68). Four patients (0.17%) were found to have selective maltase deficiency. No selective sucrase or palatinase deficiency was identified. Statistically significant differences occurred in lactase deficiency amongst patients of different races. In conclusion, lactase deficiency is a relatively common finding in children undergoing EGD though at no increased rate amongst the IBD patient population. Disaccharidase testing should be considered in pediatric patients undergoing EGD.
Bone adapts to physical forces and this process is dependent on osteocyte mechanotransduction. One way osteocytes sense mechanical stimulation is through the primary cilium, a sensory organelle that triggers intracellular signaling cascades in response to fluid shear. Our lab previously determined that flow-induced ciliary Ca2+ influx and changes in cytosolic cAMP levels are critical for osteogenesis. We also identified two proteins important for osteocyte mechanotransduction: transient receptor potential vanilloid 4 (TRPV4) and adenylyl cyclase 6 (AC6). Interestingly, disrupting the Ca2+-binding ability of these proteins results in loss of function. Although knockdowns of TRPV4 and AC6 disrupt osteogenesis, there is no definitive evidence linking them to Ca2+/cAMP dynamics that facilitate osteocyte mechanotransduction. We therefore transfected MLO-Y4 osteocytes with AC3/6 and TRPV4 overexpression plasmids that fail to interact with Ca2+ and observed the response to fluid shear. Indeed, mutant groups exhibited adverse changes in cAMP and lower mRNA expression of an osteogenic marker, COX-2, at the onset of flow. This pattern persisted for AC3 and TRPV4 but we detected no difference in AC6 at longer exposure to flow. These results suggest TRPV4 and ACs mediate Ca2+/cAMP dynamics that are important for osteocyte mechanotransduction. These mechanisms are potential targets for therapeutics to combat bone loss and should be investigated further.
AIM:To evaluate the impact of a stress management program on weight loss, depression, anxiety and stress as well as on the adoption of healthy lifestyle in adults with obesity. METHODS:Adults with obesity who sought help for weight loss at a medical obesity clinic were consecutively enrolled in the study and were randomly assigned to the intervention or control group. All participants received standard instructions for a healthy lifestyle. The intervention group attended an 8-week stress management program that comprised diaphragmatic breathing, progressive muscle relaxation, guided visualization and instructions about healthy nutrition/dietary habits. Anthropometric parameters were assessed and several questionnaires were completed by all participants, at the beginning and at the end of the study. RESULTS:A total of 45 adults (mean age±SD 45.7±10.55 years) with obesity were enrolled in the study; 22 in the intervention group and 23 in the control group. Participants in the two groups were matched for age and BMI. Participants in the intervention group achieved a significantly larger reduction in BMI compared to the control group (ΔBMI -3.1 vs. -1.74 kg/m2 respectively, P<0.001). In addition, they displayed ameliorated depression and anxiety scores and a reduction in the health locus of control based on chance.
A suite of computer programs has been developed under the general name Thetis, for monitoring structural changes during molecular dynamics (MD) simulations on proteins. Conformational analysis includes estimation of structural similarities during the simulation and analysis of the secondary structure with emphasis on helices. In contrast to available freeware dealing with MD snapshots, Thetis can be used on a series of consecutive MD structures, thus allowing a detailed conformational analysis over the time course of the simulation.
Aluminum salts are widely used as the active antiperspirant in underarm cosmetic. Experimental observations indicate that its long term application may correlate with breast cancer development and progression. This action is proposed to be attributed, among others, to aluminum possible estrogen-like activities. In this study we showed that aluminum, in the form of aluminum chlorohydrate (ACH), caused increase in estrogen receptor alpha (ERα) protein levels, in ERα-positive MCF-7 cells. This effect was accompanied by moderate activation of Estrogen Response Elements (ERE)-driven reporter gene expression and 20%-50% increase in certain estrogen responsive, ERE-independent genes expression. Genes affected were ERα, p53, cyclin D1, and c-fos, crucial regulators of breast cancer development and progression. ACH-induced genes expression was eliminated in the presence of the estrogen antagonist: ICI 182780, in MCF-7 cells, whereas it was not observed in ERα-negative MDA-MB-231 breast cancer cells, indicating aluminum interference with estrogen signaling. Moreover, ACH caused increase in the perinuclear localization of estrogen receptor alpha in MCF-7 breast cancer cells and increase in the mitochondrial Bcl-2 protein, possibly affecting receptors-mediated mitochondrial actions and mitochondrial-dependent apoptosis. ACH-induced perinuclear localization of estrogen receptor beta was also observed in MDA-MB-231. Our findings indicate that aluminum actions on estrogen receptors protein level and subcellular localization possibly affect receptors-mediated actions and thus, aluminum interference with estrogen signaling.
BACKGROUNDMany rapid nongenomic glucocorticoid actions are mediated by membrane-bound glucocorticoid receptors (GRs). S-palmitoylation is a lipid post-translational modification that mediates the membrane localization of some steroid receptors. A highly homologous amino acid sequence (663YLCM KTLLL671) is present in the ligand-binding domain of hGRα, suggesting that hGRα might also undergo S-palmitoylation.AIMTo investigate the role of the motif 663YLCMKTLLL671 in membrane localization of the hGRα and in mediating rapid nongenomic glucocorticoid signaling.METHODS AND RESULTSWe showed that the mutant receptors hGRαY663A, hGRαC665A and hGRαLL670/671AA, and the addition of the palmitoylation inhibitor 2-bromopalmitate did not prevent membrane localization of hGRα and co-localization with caveolin-1, and did not influence the biphasic activation of mitogen-activated protein kinase (MAPK) signaling pathway in the early time points. Finally, the hGRα was not shown to undergo S-palmitoylation.CONCLUSIONSThe motif 663YLCMKTLLL671 does not play a role in membrane localization of hGRα and does not mediate the nongenomic glucocorticoid actions.
At the end of the 1980s, the hepatitis C virus (HCV) was cloned and formally identified as the cause of the majority of non-A and non-B hepatitis cases. Today, around 170 million people worldwide are infected with HCV, making it five times more common than infection with the human immunodeficiency virus (HIV). Several methods exist which mediate the spread of infection. One of the most common and efficient is sharing or re-using injecting equipment; studies have indicated that 80-90% of individuals in some populations of intravenous drug users test positive in serum HCV assays. Contracting HCV from infected blood transfusions was also a major cause of infection before screening tests were introduced in the early 1990s. Other possible, but less common, methods of infection transmission include mother-to-child during pregnancy, sexual contact and nosocomial acquisition (for example between surgical or dialysis patients). It appears that concurrent HIV-1 infection increases the risk of HCV transmission via the mother-to-child or sexual routes.
Viral binding and entry provides the first trigger of a cell death response and thus how human cytomegalovirus (HCMV) evades this - particularly during latent infection where a very limited pattern of gene expression is observed - is less well understood. It has been demonstrated that the activation of cellular signalling pathways upon virus binding promotes the survival of latently infected cells by the activation of cell encoded anti-apoptotic responses. In CD34+ cells, a major site of HCMV latency, ERK signalling is important for survival and we now show that the activation of this pathway impacts on multiple aspects of cell death pathways. The data illustrate that HCMV infection triggers activation of pro-apoptotic Bak which is then countered through multiple ERK-dependent functions. Specifically, ERK promotes ELK1 mediated transcription of the key survival molecule MCL-1, along with a concomitant decrease of the pro-apoptotic BIM and PUMA proteins. Finally, we show that the elimination of ELK-1 from CD34+ cells results in elevated Bak activation in response to viral infection, resulting in cell death. Taken together, these data begin to shed light on the poly-functional response elicited by HCMV via ERK-MAPK to promote cell survival.
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, hyperlipidemia and diabetes in relation to the severity of frailty in the elderly.
Current treatment options for castration-resistant prostate cancer (CRPC) are limited. In this study, a high-throughput screen of 4910 drugs and drug-like molecules was performed to identify antiproliferative compounds in androgen ablated prostate cancer cells. The effect of compounds on cell viability was compared in androgen ablated LNCaP prostate cancer cells and in LNCaP cells grown in presence of androgens as well as in two non-malignant prostate epithelial cells (RWPE-1 and EP156T). Validation experiments of cancer specific anti-proliferative compounds indicated pinosylvin methyl ether (PSME) and tanshinone IIA as potent inhibitors of androgen ablated LNCaP cell proliferation. PSME is a stilbene compound with no previously described anti-neoplastic activity whereas tanshinone IIA is currently used in cardiovascular disorders and proposed as a cancer drug. To gain insights into growth inhibitory mechanisms in CRPC, genome-wide gene expression analysis was performed in PSME- and tanshinone IIA-exposed cells. Both compounds altered the expression of genes involved in cell cycle and steroid and cholesterol biosynthesis in androgen ablated LNCaP cells. Decrease in androgen signalling was confirmed by reduced expression of androgen receptor and prostate specific antigen in PSME- or tanshinone IIA-exposed cells. Taken together, this systematic screen identified a novel anti-proliferative agent, PSME, for CRPC. Moreover, our screen confirmed tanshinone IIA as well as several other compounds as potential prostate cancer growth inhibitors also in androgen ablated prostate cancer cells. These results provide valuable starting points for preclinical and clinical studies for CRPC treatment.
BACKGROUND:Obesity in childhood and adolescence represents a major health problem of our century, and accounts for a significant increase in morbidity and mortality in adulthood. In addition to the increased consumption of calories and lack of exercise, accumulating evidence suggests that childhood obesity is strongly associated with prolonged and excessive activation of the stress system.AIM:The aim of our study was to assess the effectiveness of a stress-management intervention program, which included progressive muscle relaxation, diaphragmatic breathing, guided imagery and cognitive restructuring, in overweight and obese children and adolescents.METHODS:Forty-nine children and adolescents (mean age ± SEM: 11.15 ± 1.48 years) were prospectively recruited to participate in this randomized controlled study. Of those, 23 participants were assigned into the intervention group, while 26 participants represented the control group. Anthropometric measurements were recorded at the beginning and at the end of the study, and participants were asked to complete the Screen for Child Anxiety Related Disorders (S.C.A.R.E.D.), the Child Depression Inventory (C.D.I.), the Child Behavior Checklist (C.B.C.L.) and the Youth Self Report (Y.S.R.).RESULTS:The applied stress-management methods resulted in a significant reduction in the body mass index (BMI) in the intervention group compared with the control group [ΔBMI=1.18 vs 0.10 kg/m2 (p<0.001)]. In addition to BMI, these methods ameliorated depression and anxiety, and reduced the internalizing and externalizing problems in the intervention group.CONCLUSIONS:Our study demonstrated that the application of an 8-week stress management program could facilitate weight loss in Greek overweight and obese children and adolescents. Further larger studies are required to evaluate the effectiveness of stress-management methods in overweight and obese subjects.
Nucleophosmin (NPM) is a ubiquitously expressed phosphoprotein involved in many cellular processes. Phosphorylation is considered the major regulatory mechanism of the NPM protein, associated with diverse cellular events. In this study, we characterized the phosphorylation status of several physiological phosphorylation sites of NPM, especially the newly confirmed in vivo site threonine 95 (Thr95). NPM-Thr95 exhibits a transient and cell cycle-dependent phosphorylation state compared to several other in vivo phosphorylation sites examined, including Ser4, Thr199 and Thr234/Thr237. In addition, we characterized a functional interaction between NPM and the peptidyl-prolyl isomerase Pin1, which specifically bind to each other during mitosis. The demonstration of this binding represents a novel post-phosphorylation regulatory mechanism for NPM that has not been investigated before. Mutated Pin1 putative binding sites result in defected cell division and reduced number of mitotic cells, suggesting that post-phosphorylation is important for NPM in regulating cell cycle progression.
