Showing papers by "Elias Castanas published in 2016"

Estrogen anti-inflammatory activity on human monocytes is mediated through cross-talk between estrogen receptor ERα36 and GPR30/GPER1

Abstract: Estrogens are known modulators of monocyte/macrophage functions; however, the underlying mechanism has not been clearly defined. Recently, a number of estrogen receptor molecules and splice variants were identified that exert different and sometimes opposing actions. We assessed the expression of estrogen receptors and explored their role in mediating estrogenic anti-inflammatory effects on human primary monocytes. We report that the only estrogen receptors expressed are estrogen receptor-α 36-kDa splice variant and G-protein coupled receptor 30/G-protein estrogen receptor 1, in a sex-independent manner. 17-β-Estradiol inhibits the LPS-induced IL-6 inflammatory response, resulting in inhibition of NF-κB transcriptional activity. This is achieved via a direct physical interaction of ligand-activated estrogen receptor-α 36-kDa splice variant with the p65 component of NF-κB in the nucleus. G-protein coupled receptor 30/G-protein estrogen receptor 1, which also physically interacts with estrogen receptor-α 36-kDa splice variant, acts a coregulator in this process, because its inhibition blocks the effect of estrogens on IL-6 expression. However, its activation does not mimic the effect of estrogens, on neither IL-6 nor NF-κB activity. Finally, we show that the estrogen receptor profile observed in monocytes is not modified during their differentiation to macrophages or dendritic cells in vitro and is shared in vivo by macrophages present in atherosclerotic plaques. These results position estrogen receptor-α 36-kDa splice variant and G-protein coupled receptor 30 as important players and potential therapeutic targets in monocyte/macrophage-dependent inflammatory processes.

Vitamin D levels in a large Mediterranean cohort: reconsidering normal cut-off values

Abstract: OBJECTIVE: The determination of the normal range of 25-hydroxyvitamin D [25-(OH)D], though currently based on suppression of PTH levels, still remains a controversial issue. The 25-(OH)D levels exhibit gender and seasonal variability, the latter attributed in part to changes of insolation. DESIGN: The aim of this cross-sectional study was to estimate the levels of 25-(OH)D on the island of Crete and their correlation with metabolic, hormonal and bone turnover parameters. The study was performed over a period of five years and involved 8,183 male and female individuals (8,042 analyzed). RESULTS: Our results are as follows: (1) 25-(OH)D was significantly lower than expected (19.48±9.51 and 18.01±9.01 (ng/mL±SD) in males and females, respectively); (2) seasonal variation of 25-(OH)D was observed in both sexes (females < males), with values peaking in August; (3) a decline of 25-(OH)D was evident with advancing age, with lower levels in females compared to males up to menopause and no apparent difference between the genders thereafter; (4) levels of 25-(OH)D were lower in renal function impairment, diabetes/insulin resistance and inflammation, while no correlation was detectable in thyroid dysfunction; (5) normalization of PTH levels was observed at ∼20 ng/mL 25-(OH)D. At the same cut-off level, a significant decrease of all measured bone turnover indices (b-ALP, osteocalcin and CTX) was evident. CONCLUSION: Based on the above data, it appears that a cut-off level of 25-(OH)D close to 20 ng/mL better reflects the physiology of our population.

Cord blood leptin levels in relation to child growth trajectories.

Abstract: Objective Leptin represents a potential modulator of developmental programming of childhood obesity. We investigated the association of cord blood leptin with growth trajectories from birth to early childhood. Materials/methods We used data from the prospective mother–child cohort “Rhea”, Crete, Greece. Cord blood samples from 642 neonates were collected. 578 (90%) children had complete follow up data from birth to 4 years. We measured child weight, height, waist circumference, skinfold thicknesses, blood pressure, and serum lipids, leptin, adiponectin and C-reactive protein in early childhood (median 4.2 years). We estimated growth trajectories from 3 months up to 4 years using random-effects linear-spline models. Multivariable logistic and linear regression models were used adjusting for confounders. Results Mean cord blood leptin levels were 7.3 ng/mL (standard deviation: 6.3). Children with high cord blood leptin (> 90th percentile) exhibited lower weight, height and body mass index from 6 months to early childhood. Each SD increase in cord blood leptin was associated with lower weight at the age of 4 by 242 g (95% CI: − 416, − 69). In a stratified analysis, the reverse association was observed in children born small for gestational age (p for interaction = 0.001), and in those exhibiting rapid infant growth during the first 3 months of life (p for interaction = 0.002). Cord blood leptin levels were not associated with cardiometabolic risk factors at 4 years. Conclusions Long term programming effects of in utero exposure to leptin extends beyond infancy into early childhood. Further studies are needed to explore potential effect modification by intrauterine and early infancy growth patterns.

Androgen Control in Prostate Cancer

Abstract: Research on prostate cancer has extensively advanced in the past decade, through an improved understanding for its genetic basis and risk-stratification. Molecular classification of prostate cancer into distinct subtypes and the recognition of new histologic entities promise the development of tailored-made management strategies of patients. Nowadays, various alternatives are available for clinical management of localized disease ranging from observation alone through radical prostatectomy. In patients with castration-resistant prostate cancer, the approval of new drugs for the management of metastatic disease has offered promising results improving the survival of these patients. In this context, androgen receptors (AR) remain at the epicenter of prostate cancer research holding a prominent role in the biology and therapeutic regimens of prostate cancer. As many of castration-resistant tumors retain hormone-responsiveness, AR is a clinical relevant, druggable target. However, AR paradoxically remains neglected as a prostate cancer biomarker. The great advancements in prostate cancer preclinical and clinical research, imply further improvement in clinical and translational data, for patient selection and treatment optimization. For a precision medicine-guided clinical management of prostate cancer, AR evaluation has to be implemented in companion and complementary diagnostics, as discussed here. J. Cell. Biochem. 117: 2224-2234, 2016. © 2016 Wiley Periodicals, Inc.