Publications

Immunoreactive CRH (IrCRH) is produced locally in experimentally induced and spontaneous inflammation. Where it exerts autocrine or paracrine proinflammatory effects. In addition, CRH is secreted by the human placenta, rat Leydig cells, and rat and human ovaries, where it may participate in the inflammatory processes of ovulation and luteolysis, and/or the regulation of steroidogenesis. Finally, CRH is secreted in vitro by cultured human epithelial and decidualized stromal endometrial cells. To investigate the presence of CRH in human endometrium in vivo, we examined this tissue immunohistochemically and by extraction/RIA using a polyclonal, highly specific antirat/human CRH antibody. Endometrial biopsies from 33 women, aged 23-43 yr (median age, 33.5 yr), were performed by linear endometrial curettage for diagnostic purposes at different stages of the cycle. Intense IrCRH staining was localized in the cytoplasm of cells of the endometrial glands in all samples examined. IrCRH was also found in endometrial stromal cells exhibiting decidual reaction and in local immune accessory cells. The mobility of the endometrial IrCRH molecule was similar to that of r/hCRH in reverse phase high pressure liquid chromatography. The presence of CRH in the endometrium, and more specifically in the glandular epithelium during the proliferative and secretory phases of the menstrual cycle together with its known proinflammatory properties, suggest that this neuropeptide might participate in the inflammatory-like phenomena of endometrial physiology, such as menstrual shedding, surface epithelium repair, and/or implantation of the blastocyst. The presence of CRH in decidualized stromal cells is in accordance with its previously reported production by in vitro decidualized cultured endometrial stromal cells as well as by the placental decidua.

Chronic stress is a recognized risk factor for poor health, body composition disequilibrium, impaired mental health, and deterioration of quality of life. Chronic stress-related cortisol oversecretion and circadian dysregulation and associated systemic low grade, injurious inflammation ("para-inflammation") contribute to steatosis in various metabolically active solid organs, affecting both their structure and function. The aim of this review was to summarize current knowledge on the impact of chronic stress and associated para-inflammation on skeletal muscle, bone, liver, and pancreas, leading to their steatosis. Current management of these maladaptive conditions is also included and underscored in this review.Steatosis of metabolically active solid organs is involved in various metabolic processes and considered a risk factor for chronic noncommunicable diseases, yet its role in chronic stress physiology and pathophysiology has been overlooked.Chronic stress-associated steatosis of several solid organs is generally disregarded in current clinical practice. Physicians should be alert for these steatoses and should address them adequately so as to provide appropriate medical care. New guidelines generated by learned societies are needed, along with large observational studies, to offer novel solutions to this old problem.

A high-affinity, nonpeptide radioligand for the CRHR1 was synthesized and showed distribution in rat brain consistent with CRHR1 using in vitro autoradiography. This is the first nonpeptide radiotracer combining high affinity and appropriate lipophilicity that penetrates the blood−brain barrier and hence has the potential to be used for PET imaging studies. In vivo visualization of changes in the CRH1 receptor or its occupancy would further the understanding of the pathophysiology of stress related diseases.

Objective: Cysteinyl leukotrienes potentially promote adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). In adults, 5-lipoxygenase (5-LO) is expressed by tonsillar B-lymphocytes, but conflicting data have been presented regarding 5-LO in T-lymphocytes. We hypothesized that in children with OSA, leukotriene biosynthetic enzymes [5-LO; 5-LO activating protein (FLAP); LTA4 hydrolase (LTA4H); and leukotriene C4 synthase (LTC4S)] are expressed by both T- and B-tonsillar lymphocytes. Study design: Tonsillar tissue from children with OSA or controls with recurrent tonsillitis (RT) was studied for expression of biosynthetic enzymes by RT-PCR and flow cytometry (FC). Results: Thirteen children with OSA and 12 subjects with RT were included. mRNA for all enzymes was detected in both T- and B-lymphocytes. Children with OSA had higher LTC4S mRNA copies obtained from CD19+ B-lymphocytes than subjects with RT (RT-PCR: 1.72 ± 0.14 vs. 1.14 ± 0.92; p=0.04). There were no other differences in mRNA copies for the other enzymes from T- or B-lymphocytes. In OSA participants, LTC4S + fractions of CD3+ T-lymphocytes or CD19+ B-lymphocytes were significantly higher than in children with RT (FC: 22.5 ± 13.8% vs. 11.8 ± 6.7% or 28.9 ± 18% vs. 14.5 ± 11%, respectively; p<0.05). The two groups were similar regarding T- or B-lymphocytes fractions expressing other enzymes. Conclusions: Enzymes of the leukotriene biosynthetic pathway are detected in both T- and B-tonsillar lymphocytes. Children with sleep apnea and hypertrophic tonsils have enhanced expression of LTC4S, a key enzyme for cysteinyl leukotriene synthesis.

Interleukin-12 (IL-12) is a key inducer of differentiation of uncommitted T helper (TH) cells toward the TH1 phenotype, which regulates cellular immunity, whereas IL-10 inhibits TH1 functions and potentiates TH2-regulated responses (i.e., humoral immunity). To examine the potential effects of stress on TH1/TH2 balance, we studied the ability of three prototype stress hormones-dexamethasone (a synthetic glucocorticoid) and the catecholamines norepinephrine and epinephrine-to alter the production of IL-12 (p70) and IL-10 induced by bacterial lipopolysaccharide (LPS) in human whole blood. Dexamethasone inhibited LPS-induced bioactive IL-12 production in a dose-dependent fashion and at physiologically relevant concentrations; it had no effect on IL-10 secretion. The glucocorticoid-induced reduction of IL-12 production was antagonized by RU 486, a glucocorticoid-receptor antagonist, suggesting that it was mediated by the glucocorticoid receptor. Norepinephrine and epinephrine also suppressed IL-12 production in a dose-dependent fashion and at physiological concentrations; both catecholamines, however, dose-dependently increased the production of IL-10. The effects of either catecholamine on IL-12 or IL-10 secretion were blocked completely by propranolol, a beta-adrenoreceptor antagonist, indicating that they were mediated by the beta-adrenergic receptor. These findings suggest that the central nervous system may regulate IL-12 and IL-10 secretion and, hence, TH1/TH2 balance via the peripheral end-effectors of the stress system. Thus, stress may cause a selective suppression of TH1 functions and a shift toward a TH2 cytokine pattern rather than generalized TH suppression. The TH1-to-TH2 shift may be responsible for the stress-induced susceptibility of the organism to certain infections. Through the same or a reciprocal mechanism, states associated with chronic hyperactivity or hypoactivity of the stress system might influence the susceptibility of an individual to certain autoimmune, allergic, infectious, or neoplastic diseases.

This monitoring system aims at increasing the resilience of the road infrastructures and ensuring reliable network availability under unfavourable conditions, such as extreme weather, landslides, and earthquakes. The main target is to combine downscaled climate change scenarios (applied to road infrastructures) with simulation tools (structural/geotechnical) and actual data (from existing and novel sensors), so as to provide the operators with an integrated tool able to support more effective management of their infrastructures at planning, maintenance and operation level. Towards this, the proposed framework aims to use high resolution modelling data for the determination and the assessment of the climatic risk of the selected, transport infrastructures and associated expected damages, use existing SHM data (from accelerometers, strain gauges etc.) with new types of sensor-generated data (computer vision) to feed the structural/geotechnical simulator, utilize tailored weather forecasts (combining seamlessly all available data sources) for specific hot-spots, providing early warnings with corresponding impact assessment in real time; develop improved multi-temporal, multi-sensor UAV, computer vision and machine learning-based damage diagnostic for diverse transport infrastructures; design and implement a Holistic Resilience Assessment Platform environment as an innovative planning tool that will permit a quantitative resilience assessment through an end-to-end simulation environment, running "what-if" impact/risk/resilience assessment scenarios. The effects of adaptation measures can be investigated by changing the hazard, exposure and vulnerability input parameters; design and implement a Common Operational Picture, including an enhanced visualisation interface and an Incident Management System. The integrated platform (and its sub-modules) will be validated in two real case studies in Spain and in Greece.

The COVID‑19 pandemic has radically changed the lives of individuals. To date, there is no specific antiviral drug available against SARS‑CoV‑2 and the recently developed vaccines are very promising; however, their influence on the pandemic remains limited. The most effective strategy to reduce the spread of the virus is social distancing and social lockdowns. All humanity is going through a period in which the health domain is at the forefront, demanding the adoption of new habits to protect individuals and public health, such as the continued use of masks and vigilant hand hygiene. Lifestyle conditions have a negative effect on the psychological and mental health of individuals, as there has been an increase in the rates of psychological stress, panic attacks, depression, violence and sleep disorders. Quarantines also have a negative impact on the socio‑economic sector, as unemployment and poverty rates have risen worldwide due to industrial production arrest and closure of businesses. Additionally, the epigenetic effect of the undergoing tension due to the pandemic and social lockdowns can cause a long‑term negative effects on human behavior and physiology. However, lockdowns and quarantines have a positive impact on the environment and energy saving due to limited human activity and transport. Thus, the aim of the present review article was to record the impact of lockdowns on the health, physical and mental, of people as well as on society and the environment.

HIV-1 accessory protein Vpr arrests host cells at the G2/M phase of the cell cycle by interacting with members of the protein family 14-3-3, which regulate the activities of “partner” molecules by binding to their phosphorylated serine or threonine residues and changing their intracellular localization and/or stability. Vpr does this by facilitating the association of 14-3-3 to its partner protein Cdc25C, independent of the latter’s phosphorylation status. Here we report that the same viral protein interfered with and altered the activity of another 14-3-3 partner molecule, Foxo3a, a subtype of the forkhead transcription factors, by inhibiting its association with 14-3-3. Foxo3a’s transcriptional activity is normally suppressed by insulin-induced translocation of this protein from the nucleus into the cytoplasm. Vpr inhibited the ability of insulin or its downstream protein kinase Akt to change the intracellular localization of Foxo3a preferentially to the cytoplasm. This HIV-1 protein also interfered with insulin-induced coprecipitation of 14-3-3 and Foxo3a in vivo and antagonized the negative effect of insulin on Foxo3a-induced transactivation of a FOXO-responsive promoter. Moreover, Vpr antagonized insulin-induced suppression of the mRNA expression of the glucose 6-phosphatase, manganese superoxide dismutase, and sterol carrier protein 2 genes, which are known targets of insulin and FOXO, in HepG2 cells. These findings indicate that Vpr interferes with the suppressive effects of insulin on FOXO-mediated transcription of target genes via 14-3-3. Vpr thus may contribute to the tissue-selective insulin resistance often observed in HIV-1–infected individuals.