Socioeconomic status and adiposity in childhood cancer survivors: A cross-sectional retrospective study.

This is a retrospective cross-sectional study examining the association between unemployment, cancer type, treatment and total body fat percentage of childhood cancer survivors recruited at St. Anne's University Hospital in Brno, Czech Republic. A total of 55 survivors aged 18-49 who were in remission of cancer and fulfilled the criteria for body composition measurements by the BIA and completed questionnaires investigating their socioeconomic status, employment status, and history. There was a significant relationship between the employment status and central nervous system-directed treatment (c2(1) = 7.53, p = 0.006, Cramér's V = 0.38) and between the type of cancer and employment status (c2(3) = 7.83, p = 0.049, Cramér's V = 0.38), the highest unemployment rate was recorded for brain and spine survivors (72.7%) compared to survivors with other diagnosis (35.7%) (uLR(1) = 4.91, p = 0.027; OR = 4.80, 95% CI:1.10-20.86, p = 0.036); these survivors did not have a significantly different body fat percentage compared to survivors with other diagnoses (t(53) = 1.29, p = 0.202, Cohen's d = 0.41) Interestingly, the survivors reporting having a partner also had a significantly higher percentage of body fat (t(53) = 2.90, p = 0.005, Cohen's d = 0.81). A linear regression model was used to model the percentage of body fat in relation to a set of selected variables and the we observed a significant effect of sex (female vs male: b = 6.37, 95% CI: 1.82-10.93, p = 0.007), partnership status (yes vs no: b = 5.65, 95% CI: 0.67-10.62, p = 0.027) and category of diagnosis (Brain and spinal column tumors vs Other solid tumors: b = 12.40, 95% CI: 0.59-24.21, p = 0.040; Brain and spinal column tumors vs Lymphoma: b = 14.02, 95% CI: 2.06-25.97, p = 0.023). Employment status and risk of adiposity in childhood cancer survivors depends on the type of treatment and diagnosis group, which may significantly impact their lifestyle and overall quality of life after treatment. Trial registration: This study was registered on July 29, 2022, at ClinicalTrials.gov (NCT05481229).

Physiological evidence of stress reduction during a summer Antarctic expedition with a significant influence of previous experience and vigor.

Antarctica provides a unique environment for studying human adaptability, characterized by controlled conditions, limited sensory stimulation, and significant challenges in logistics and communication. This longitudinal study investigates the relationship between stress indicators, with a specific focus on mean sleep heart rate, during a COVID-19 quarantine and subsequent 83 days long summer Antarctic expedition at the J. G. Mendel Czech Antarctic Station. Our novel approach includes daily recordings of sleep heart rate and weekly assessments of emotions, stress, and sleep quality. Associations between variables were analyzed using the generalized least squares method, providing unique insights into nuances of adaptation. The results support previous findings by providing empirical evidence on the stress reducing effect of Antarctic summer expedition and highlight the importance of previous experience and positive emotions, with the novel contribution of utilizing physiological data in addition to psychological measures. High-frequency sampling and combination of psychological and physiological data addresses a crucial gap in the research of stress. This study contributes valuable knowledge to the field of psychophysiology and has implications for expedition planners, research organizations, teams in action settings, pandemic prevention protocols, global crises, and long-duration spaceflight missions. Comprehensive insights promote the well-being and success of individuals in extreme conditions.

The effect of space travel on human reproductive health: a systematic review.

With increasing possibilities of multi-year missions in deep space, colonizing other planets, and space tourism, it is important to investigate the effects of space travel on human reproduction. This study aimed to systematically review and summarize the results of available literature on space travel, microgravity, and space radiation, or Earth-based spaceflight analogues impact on female and male reproductive functions in humans. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Space Biomedicine Systematic Review methods. The search was performed using three databases: PubMed, Web of Science, and Medline Complete. During the database search, 364 studies were identified. After the study selection process, 16 studies were included in the review. Five studies included female participants, and the findings show an increased risk of thromboembolism in combined oral contraceptive users, decreased decidualization, functional insufficiency of corpus luteum, and decreased progesterone and LH levels related to space travel or its simulation. Male participants were included in 13 studies. In males, reproductive health considerations focused on the decrease in testosterone and sex hormone-binding globulin levels, the ratio of male offspring, sperm motility, sperm vitality, and the increase in sperm DNA fragmentation related to space travel or its simulation. Results of this systematic review highlight the need to focus more on the astronaut's reproductive health in future research, as only 16 studies were found during the literature search, and many more research questions related to reproductive health in astronauts still need to be answered.

Unraveling adipose tissue proteomic landscapes in severe obesity: insights into metabolic complications and potential biomarkers.

In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies.NEW & NOTEWORTHY This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.

Biological factors and self-perception of stress in relation to freeze-like response in humans.

Many animals react to threatening stimuli such as a predator attacks by freezing. However, little experimental research investigated freeze response in humans. Here, we have employed practices commonly used in self-defense training to create two unique scenarios simulating armed physical threat. Sixty healthy men volunteers divided into three groups of twenty (untrained, trained but unexperienced, trained and experienced) underwent these scenarios accompanied by measurement of biochemical, physiological, and psychological markers of stress. Our results show that untrained individuals exhibit stronger freezing reactions, while highly skilled participants display the lowest propensity for freezing, especially in high-intensity scenarios. Moreover, the study shows variations in anxiety levels and selected biomarkers, with cortisol and osteocalcin showing different patterns in low and high-intensity scenarios, and suggests a complex interplay between these factors, electrodermal activity, and stress perception.

Learning mitigates genetic drift.

Genetic drift is a basic evolutionary principle describing random changes in allelic frequencies, with far-reaching consequences in various topics ranging from species conservation efforts to speciation. The conventional approach assumes that genetic drift has the same effect on all populations undergoing the same changes in size, regardless of different non-reproductive behaviors and history of the populations. However, here we reason that processes leading to a systematic increase of individuals` chances of survival, such as learning or immunological memory, can mitigate loss of genetic diversity caused by genetic drift even if the overall mortality rate in the population does not change. We further test this notion in an agent-based model with overlapping generations, monitoring allele numbers in a population of prey, either able or not able to learn from successfully escaping predators' attacks. Importantly, both these populations start with the same effective size and have the same and constant overall mortality rates. Our results demonstrate that even under these conditions, learning can mitigate loss of genetic diversity caused by drift, by creating a pool of harder-to-die individuals that protect alleles they carry from extinction. Furthermore, this effect holds regardless if the population is haploid or diploid or whether it reproduces sexually or asexually. These findings may be of importance not only for basic evolutionary theory but also for other fields using the concept of genetic drift.

Polymorphism rs7079 in miR-31/-584 Binding Site in Angiotensinogen Gene Associates with Earlier Onset of Coronary Artery Disease in Central European Population.

Angiotensinogen (AGT) represents a key component of the renin-angiotensin-aldosterone system (RAAS). Polymorphisms in the 3' untranslated region (3'UTR) of the AGT gene may alter miRNA binding and cause disbalance in the RAAS. Within this study, we evaluated the possible association of AGT +11525C/A (rs7079) with the clinical characteristics of patients with coronary artery diseases (CAD). Selective coronarography was performed in 652 consecutive CAD patients. Clinical characteristics of the patients, together with peripheral blood samples for DNA isolation, were collected. The genotyping of rs7079 polymorphism was performed with TaqMan® SNP Genotyping Assays. We observed that patients with the CC genotype were referred for coronarography at a younger age compared to those with the AA+CA genotypes (CC vs. AA+CA: 59.1 ± 9.64 vs. 60.91 ± 9.5 (years), p = 0.045). Moreover, according to the logistic regression model, patients with the CC genotype presented more often with restenosis than those with the CA genotype (p = 0.0081). In conclusion, CC homozygotes for rs7079 present with CAD symptoms at a younger age compared with those with the AA+CA genotype, and they are more prone to present with restenosis compared with heterozygotes.

Osteocalcin levels decrease during the treatment of an acute depressive episode.

Objectives: Osteocalcin is a protein secreted by osteoblasts with a versatile endocrine role. Several domains in which it plays a role-stress response, monoamine synthesis, and cognitive functioning-are implicated also in the pathophysiology of major depressive disorder. In search of possible objective biomarkers of depression, the aim of the study was to assess the relationship between osteocalcin and depressive symptoms during the treatment of depressive episode. Methods: The study included female inpatients with at least moderate depressive episode. In these patients, depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), and osteocalcin levels were assessed before the stabilization of antidepressive treatment and after 6 weeks. Relationships between osteocalcin levels and symptoms were analyzed with mixed-effect and linear models, taking into account age, menopausal status, and body mass index. Results: In 11 out of 13 enrolled inpatients, osteocalcin levels decreased during the first 6 weeks of treatment; this decrease was significant according to the mixed-effects model (t = -2.345, p = 0.019). According to the linear model, this decrease was significantly associated with reduction in depressive symptom severity (t = 2.673, p = 0.028). Osteocalcin was not associated with initial depressive symptom severity, and initial osteocalcin levels did not predict response to treatment. Limitations of the study include low sample size and inclusion of both pre- and postmenopausal women of various ages. Conclusions: This preliminary study suggests that osteocalcin may be a candidate biomarker of antidepressive treatment response and that this topic warrants further investigation.

GDF11 inhibits adipogenesis and improves mature adipocytes metabolic function via WNT/ß-catenin and ALK5/SMAD2/3 pathways.

OBJECTIVE: GDF11 is a member of the TGF-ß superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue. METHODS: We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines. RESULTS: Our in vivo experiments employing GDF11 treatment in ob/ob mice showed improved glucose/insulin homeostasis, decreased weight gain and white adipocyte size. Furthermore, GDF11 treatment inhibited adipogenesis in pre-adipocytes by ALK5-SMAD2/3 activation in cooperation with the WNT/ß-catenin pathway, whose inhibition resulted in adipogenic differentiation. Lastly, we observed significantly elevated levels of the adipokine hormone adiponectin and increased glucose uptake by mature adipocytes upon GDF11 exposure. CONCLUSION: We show evidence that link GDF11 to adipogenic differentiation, glucose, and insulin homeostasis, which are pointing towards potential beneficial effects of GDF11-based "anti-obesity" therapy.

Follistatin-like 1 and its paralogs in heart development and cardiovascular disease.

Cardiovascular diseases (CVDs) are a group of disorders affecting the heart and blood vessels and a leading cause of death worldwide. Thus, there is a need to identify new cardiokines that may protect the heart from damage as reported in GBD 2017 Causes of Death Collaborators (2018) (The Lancet 392:1736-1788). Follistatin-like 1 (FSTL1) is a cardiokine that is highly expressed in the heart and released to the serum after cardiac injury where it is associated with CVD and predicts poor outcome. The action of FSTL1 likely depends not only on the tissue source but also post-translation modifications that are target tissue- and cell-specific. Animal studies examining the effect of FSTL1 in various models of heart disease have exploded over the past 15 years and primarily report a protective effect spanning from inhibiting inflammation via transforming growth factor, preventing remodeling and fibrosis to promoting angiogenesis and hypertrophy. A better understanding of FSTL1 and its homologs is needed to determine whether this protein could be a useful novel biomarker to predict poor outcome and death and whether it has therapeutic potential. The aim of this review is to provide a comprehensive description of the literature for this family of proteins in order to better understand their role in normal physiology and CVD.

Association of Picky Eating with Weight and Height-The European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ).

OBJECTIVE: This study aimed to evaluate whether preschool children identified as picky eaters showed differences in anthropometric characteristics (weight and height) from their non-picky peers at 15 years of age. DESIGN: This study was performed among the cohort members of the EL- SPAC-CZ study, a longitudinal study of pregnancy and childhood. The analysis included 2068 children (997 girls and 1071 boys) followed between births and 15 years of age. Picky eaters were identified at 1.5, 3, and 5 years of age. Anthropometric characteristics were measured at 15 years of age (15 years). RESULTS: Picky eaters (n = 346; 16.7%) had a lower weight and height than non-picky eaters (n = 1722; 83.3%) at 15 years. This difference in weight and height was maintained after controlling for sex of the child, birth weight, birth length, maternal education, family structure at 15 years, and maternal age at childbirth. The picky children were on average 2.3 kg lighter and 0.8 cm shorter than non- picky children at 15 years. CONCLUSIONS: Persistent picky eating in preschool children is related to lower weight and height at 15 years of age in ELSPAC-CZ study.

Proteomic Signatures of Human Visceral and Subcutaneous Adipocytes.

CONTEXT: Adipose tissue distribution is a key factor influencing metabolic health and risk in obesity-associated comorbidities. OBJECTIVE: Here we aim to compare the proteomic profiles of mature adipocytes from different depots. METHODS: Abdominal subcutaneous (SA) and omental visceral adipocytes (VA) were isolated from paired adipose tissue biopsies obtained during bariatric surgery on 19 severely obese women (body mass index > 30 kg/m2) and analyzed using state-of-the-art mass spectrometry. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to investigate proteome signature properties and to examine a possible association of the protein expression with the clinical data. RESULTS: We identified 3686 protein groups and found 1140 differentially expressed proteins (adj. P value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. We provide a global protein profile of abdominal SA and omental VA, present the most differentially expressed pathways and processes distinguishing SA from VA, and correlate them with clinical and body composition data. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA. CONCLUSION: Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity.

Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide. With no Food and Drug Administration approved drugs, current treatment options include dietary restrictions and lifestyle modification. NAFLD is closely associated with metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia. Hence, clinically various pharmacological approaches using existing drugs such as antidiabetic, anti-obesity, antioxidants, and cytoprotective agents have been considered in the management of NAFLD and nonalcoholic steatohepatitis (NASH). However, several pharmacological therapies aiming to alleviate NAFLD-NASH are currently being examined at various phases of clinical trials. Emerging data from these studies with drugs targeting diverse molecular mechanisms show promising outcomes. This review summarizes the current understanding of the pathogenic mechanisms of NAFLD and provides an insight into the pharmacological targets and emerging therapeutics with specific interventional mechanisms. In addition, we also discuss the importance and utility of new approach methodologies and regulatory perspectives for NAFLD-NASH drug development.

Dietary patterns and birth outcomes in the ELSPAC pregnancy cohort.

OBJECTIVES: The aim of this study was to identify dietary patterns in a Czech pregnancy cohort established in the early postcommunist era and investigate associations between dietary patterns, maternal characteristics and birth outcomes. METHODS: Pregnant women were recruited for the Czech part of the European Longitudinal Study of Pregnancy and Childhood. A self-reported questionnaire answered in late pregnancy was used to assess information about the weekly intake of 43 food items. Information about birth outcomes (birth weight, height, ponderal index, head circumference, cephalisation index, gestational length and Apgar score) was obtained from the National Registry of Newborns. Complete details on diet and birth outcomes were available for 4320 mother-infant pairs. RESULTS AND CONCLUSION: The food items were aggregated into 28 variables and used for extraction of two dietary patterns by principal component factor analysis. The patterns were denoted 'unhealthy' and 'healthy/traditional' based on the food items with the highest factor loadings on each pattern. The 'unhealthy' pattern had high positive loadings on meat, processed food and confectionaries. In contrast, the 'healthy/traditional' pattern had high positive loadings on vegetables, dairy, fruits and wholemeal bread. Following adjustment for covariates, we found that high adherence to the unhealthy pattern (expressed as beta for 1 unit increase in pattern score), that is, the higher consumption of less healthy foods, was associated with lower birth weight: -23.8 g (95% CI -44.4 to -3.2) and length: -0.10 cm (95% CI -0.19 to -0.01) and increased cephalisation index: 0.91 µm/g (95% CI 0.23 to 1.60). The 'healthy/traditional' pattern was not associated with any birth outcomes. This study supports the recommendation to eat a healthy and balanced diet during pregnancy.

Sex and age differences in sST2 in cardiovascular disease.

Aims: The goal of this study was to determine whether sex and age differences exist for soluble ST2 (sST2) for several cardiovascular diseases (CVDs). Methods: We examined sST2 levels using an ELISA kit for myocarditis (n = 303), cardiomyopathy (n = 293), coronary artery disease (CAD) (n = 239), myocardial infarct (MI) (n = 159), and congestive heart failure (CHF) (n = 286) and compared them to controls that did not have CVDs (n = 234). Results: Myocarditis occurred in this study in relatively young patients around age 40 while the other CVDs occurred more often in older individuals around age 60. We observed a sex difference in sST2 by age only in myocarditis patients (men aged 38, women 46, p = 0.0002), but not for other CVDs. Sera sST2 levels were significantly elevated compared to age-matched controls for all CVDs: myocarditis (p ≤ 0.0001), cardiomyopathy (p = 0.0009), CAD (p = 0.03), MI (p = 0.034), and CHF (p < 0.0001) driven by elevated sST2 levels in females for all CVDs except myocarditis, which was elevated in both females (p = 0.002) and males (p ≤ 0.0001). Sex differences in sST2 levels were found for myocarditis and cardiomyopathy but no other CVDs and were higher in males (myocarditis p = 0.0035; cardiomyopathy p = 0.0047). sST2 levels were higher in women with myocarditis over 50 years of age compared to men (p = 0.0004) or women under 50 years of age (p = 0.015). In cardiomyopathy and MI patients, men over 50 had significantly higher levels of sST2 than women (p = 0.012 and p = 0.043, respectively) but sex and age differences were not detected in other CVDs. However, women with cardiomyopathy that experienced early menopause had higher sST2 levels than those who underwent menopause at a natural age range (p = 0.02). Conclusion: We found that sex and age differences in sera sST2 exist for myocarditis, cardiomyopathy, and MI, but were not observed in other CVDs including CAD and CHF. These initial findings in patients with self-reported CVDs indicate that more research is needed into sex and age differences in sST2 levels in individual CVDs.

Homeostatic model of human thermoregulation with bi-stability.

All homoiothermic organisms are capable of maintaining a stable body temperature using various negative feedback mechanisms. However, current models cannot satisfactorily describe the thermal adaptation of homoiothermic living systems in a physiologically meaningful way. Previously, we introduced stress entropic load, a novel variable designed to quantify adaptation costs, i.e. the stress of the organism, using a thermodynamic approach. In this study, we use stress entropic load as a starting point for the construction of a novel dynamical model of human thermoregulation. This model exhibits bi-stable mechanisms, a physiologically plausible features which has thus far not been demonstrated using a mathematical model. This finding allows us to predict critical points at which a living system, in this case a human body, may proceed towards two stabilities, only one of which is compatible with being alive. In the future, this may allow us to quantify not only the direction but rather the extent of therapeutic intervention in critical care patients.

Birth weight rather than birth length is associated with childhood behavioural problems in a Czech ELSPAC cohort.

Many physical and psychological characteristics are influenced by prenatal development. Some studies have located links between low birth parameters and behavioural problems, with the latter in turn associated with educational progress, career success, overall health, and subsequent life events. However, few studies have investigated whether this association also applies to children in the normal birth growth range. This study thus investigates the relationship between normal-range birth length, weight, and behavioural problems at the age of seven. We use data from the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) cohort, which provides comprehensive insight into a post-communist country undergoing a period of economic transition. Childhood behavioural problems were measured in 1,796 children using the Strengths and Difficulties Questionnaire. Associations were modelled using weighted logistic regression. Birth weight was found to be linked to the total difficulties score, hyperactivity, and peer relationship problems subscales in a fully adjusted model while birth length was not significantly associated with any subscale in the fully adjusted model. We thus conclude that normal-range birth weight is associated with behavioural problems. It can therefore be assumed that the odds of behavioural problems and their consequences can be mitigated by preventive programs targeting pregnant women and children with lower but still normal weight.

Predation has small, short-term, and in certain conditions random effects on the evolution of aging.

BACKGROUND: The pace of aging varies considerably in nature. The best-known explanation of the evolution of specific rates of aging is the Williams' hypothesis suggesting that the aging rate should correlate with the level of extrinsic mortality. However, the current evidence is inconclusive with various examples where the Williams' hypothesis seems to be correct and where it doesn't. Here we explore the relationship between extrinsic mortality and aging rate by developing a simulation model of the evolution of aging rate in prey subject to predation. RESULTS: Our results suggest that more intense predation leads to the evolution of faster pace of aging in prey. However, this effect slowly vanishes when the predator diet breadth is allowed to evolve, too. Furthermore, in our model, the evolution of a specific aging rate is driven mainly by a single parameter, the strength of a trade-off between aging and fecundity. Indeed, in the absence of this trade-off the evolutionary impacts of predation on the prey aging rate appear random. CONCLUSIONS: We show that the William's hypothesis appears valid when there is a trade-off between aging and fecundity and predators and prey do not coevolve. However, we also show that when the prey and predators coevolve or if there is no trade-off between aging and fecundity the William`s hypothesis is no longer applicable.

MicroRNAs as theranostic markers in cardiac allograft transplantation: from murine models to clinical practice.

Congestive heart failure affects about 23 million people worldwide, and cardiac allograft transplantation remains one of the last options for patients with terminal refractory heart failure. Besides the infectious or oncological complications, the prognosis of patients after heart transplantation is affected by acute cellular or antibody-mediated rejection and allograft vasculopathy development. Current monitoring of both conditions requires the performance of invasive procedures (endomyocardial biopsy sampling and coronary angiography or optical coherence tomography, respectively) that are costly, time-demanding, and non-comfortable for the patient. Within this narrative review, we focus on the potential pathophysiological and clinical roles of microRNAs (miRNAs, miRs) in the field of cardiac allograft transplantation. Firstly, we provide a general introduction about the status of cardiac allograft function monitoring and the discovery of miRNAs as post-transcriptional regulators of gene expression and clinically relevant biomarkers found in the extracellular fluid. After this general introduction, information from animal and human studies are summarized to underline the importance of miRNAs both in the pathophysiology of the rejection process, the possibility of its modulation by altering miRNAs levels, and last but not least, about the use of miRNAs in the clinical practice to diagnose or predict the rejection occurrence.

Interacting effects of the MAM model of schizophrenia and antipsychotic treatment: Untargeted proteomics approach in adipose tissue.

Schizophrenia is a severe neuropsychiatric disease associated with substantially higher mortality. Reduced life expectancy in schizophrenia relates to an increased prevalence of metabolic disturbance, and antipsychotic medication is a major contributor. Molecular mechanisms underlying adverse metabolic effects of antipsychotics are not fully understood; however, adipose tissue homeostasis deregulation appears to be a critical factor. We employed mass spectrometry-based untargeted proteomics to assess the effect of chronic olanzapine, risperidone, and haloperidol treatment in visceral adipose tissue of prenatally methylazoxymethanol (MAM) acetate exposed rats, a well-validated neurodevelopmental animal model of schizophrenia. Bioinformatics analysis of differentially expressed proteins was performed to highlight the pathways affected by MAM and the antipsychotics treatment. MAM model was associated with the deregulation of the TOR (target of rapamycin) signalling pathway. Notably, alterations in protein expression triggered by antipsychotics were observed only in schizophrenia-like MAM animals where we revealed hundreds of affected proteins according to our two-fold threshold, but not in control animals. Treatments with all antipsychotics in MAM rats resulted in the downregulation of mRNA processing and splicing, while drug-specific effects included among others upregulation of insulin resistance (olanzapine), upregulation of fatty acid metabolism (risperidone), and upregulation of nucleic acid metabolism (haloperidol). Our data indicate that deregulation of several energetic and metabolic pathways in adipose tissue is associated with APs administration and is prominent in MAM schizophrenia-like model but not in control animals.