Both Hsd20b2.L and Hsd20b2.S catalyzed the 20β-reduction of further C21 steroids (17α-hydroxyprogesterone, progesterone, 11-deoxycortisol, 11-deoxycorticosterone), while only Hsd20b2.S was able to convert corticosterone and cortisol to their 20β-reduced metabolites. Estrone was only a poor and androstenedione no substrate for both enzymes. Our results demonstrate multispecificity of 20β-HSD type 2 enzymes from X. laevis similar to other teleost 20β-HSD type 2 enzymes. X. laevis 20β-HSD type 2 enzymes are probably involved in steroid catabolism and in the generation of pheromones for intraspecies communication. A role in oocyte maturation is unlikely.Breast cancer is the leading cause of cancer-related death in women worldwide. In the last years, cannabinoids have gained attention in the clinical setting and clinical trials with cannabinoid-based preparations are underway. However, contradictory anti-tumour properties have also been reported. Thus, the elucidation of the molecular mechanisms behind their anti-tumour efficacy is crucial to better understand its therapeutic potential. Considering this, our work aims to clarify the molecular mechanisms underlying the anti-cancer properties of the endocannabinoid anandamide (AEA) and of the phytocannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), in estrogen receptor-positive (ER+) breast cancer cells that overexpress aromatase (MCF-7aro). Their in vitro effects on cell proliferation, cell death and activity/expression of aromatase, ERα, ERβ and AR were investigated. Our results demonstrated that cannabinoids disrupted MCF-7aro cell cycle progression. Unlike AEA and THC that induced apoptosis, CBD triggered autophagy to promote apoptotic cell death. Interestingly, all cannabinoids reduced aromatase and ERα expression levels in cells. On the other hand, AEA and CBD not only exhibited high anti-aromatase activity but also induced up-regulation of ERβ. Therefore, all cannabinoids, albeit by different actions, target aromatase and ERs, impairing, in that way, the growth of ER+ breast cancer cells, which is dependent on estrogen signalling. As aromatase and ERs are key targets for ER+ breast cancer treatment, cannabinoids can be considered as potential and attractive therapeutic compounds for this type of cancer, being CBD the most promising one. Thus, from an in vitro perspective, this work may contribute to the growing mass of evidence of cannabinoids and cannabinoids-based medicines as potential anti-cancer drugs.Glucocorticoid (GC) receptor (GR) is a key transcription factor (TF) that regulates vital metabolic and anti-inflammatory processes. We have identified BCL6 corepressor (BCOR) as a dexamethasone-stimulated interaction partner of GR. BCOR is a component of non-canonical polycomb repressor complex 1.1 (ncPCR1.1) and linked to different developmental disorders and cancers, but the role of BCOR in GC signaling is poorly characterized. Here, using ChIP-seq we show that, GC induces genome-wide redistribution of BCOR chromatin binding towards GR-occupied enhancers in HEK293 cells. As assessed by RNA-seq, depletion of BCOR altered the expression of hundreds of GC-regulated genes, especially the ones linked to TNF signaling, GR signaling and cell migration pathways. Biotinylation-based proximity mapping revealed that GR and BCOR share several interacting partners, including nuclear receptor corepressor NCOR1. ChIP-seq showed that the NCOR1 co-occurs with both BCOR and GR on a subset of enhancers upon GC treatment.  https://www.selleckchem.com/products/ly333531.html  Simultaneous depletion of BCOR and NCOR1 influenced GR target gene expression in a combinatorial and gene-specific manner. Finally, we show using live cell imaging that the depletion of BCOR together with NCOR1 markedly enhances cell migration. Collectively, our data suggest BCOR as an important gene and pathway selective coregulator of GR transcriptional activity.
  to evaluate the effect of home confinement related to COVID-19 lockdown on metabolic control in subjects with T2DM in Italy.
 
  we evaluated the metabolic profile of 304 individuals with T2DM (65% males; age 69±9years; diabetes duration 16±10years) attending our Diabetes Unit early at the end of lockdown period (June 8 to July 7, 2020) and compared it with the latest one recorded before lockdown.
 
  There was no significant difference in fasting plasma glucose (8.6±2.1 vs 8.8±2.5mmol/L; P=0.353) and HbA1c (7.1±0.9 vs 7.1±0.9%; P=0.600) before and after lockdown. Worsening of glycaemic control (i.e., ΔHbA1c≥0.5%) occurred more frequently in older patients (32.2% in>80years vs 21.3% in 61-80years vs 9.3% in<60years; P=0.05) and in insulin users (28.8 vs 16.5%; P=0.012). On multivariable analysis, age>80years (OR 4.62; 95%CI 1.22-16.07) and insulin therapy (OR 1.96; 95%CI 1.10-3.50) remained independently associated to worsening in glycaemic control.
 
  Home confinement related to COVID-19 lockdown did not exert a negative effect on glycaemic control in patients with T2DM. However, age and insulin therapy can identify patients at greatest risk of deterioration of glycaemic control.
 Home confinement related to COVID-19 lockdown did not exert a negative effect on glycaemic control in patients with T2DM. However, age and insulin therapy can identify patients at greatest risk of deterioration of glycaemic control.
  To use latent class analysis to identify unobservable subpopulations amongst the heterogeneous population and explore the relationship between subpopulations and incident diabetes among Chinese adults.
 
  The retrospective study included 32,312 Chinese adults without diabetes at baseline. Latent class indicators included demographic and clinical variables. The outcome was incident diabetes. The relationship between latent class and outcome was evaluated with Cox proportional hazard regression analysis.
 
  After screening, the two-class latent class model best fits the population. Participants in class 2 are characterized by higher age, body mass index, systolic and diastolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, serum creatinine, serum urea nitrogen, alanine aminotransferase, and a higher proportion of males, ever/current smokers and drinkers, but lower high-density lipoprotein cholesterol and a lower proportion of family history of diabetes.