Nelsonsanford9972

Breast cancer (BC) is the second leading cause of cancer deaths among women. DEK is a known oncoprotein that is highly expressed in over 60% of breast cancers and is an independent marker of poor prognosis. However, the molecular mechanisms by which DEK promotes tumor progression are poorly understood. To identify novel oncogenic functions of DEK, we performed RNA-Seq analysis on isogenic Dek-knockout and complemented murine BC cells. Gene ontology analyses identified gene sets associated with immune system regulation and cytokine-mediated signaling and differential cytokine and chemokine expression was confirmed across Dek-proficient versus Dek-deficient cells. By exposing murine bone marrow-derived macrophages (BMDM) to tumor cell conditioned media (TCM) to mimic a tumor microenvironment, we showed that Dek-expressing breast cancer cells produce a cytokine milieu, including up-regulated Tslp and Ccl5 and down-regulated Cxcl1, Il-6, and GM-CSF, that drives the M2 polarization of macrophages. We validated this finding in primary murine mammary tumors and show that Dek expression in vivo is also associated with increased expression of M2 macrophage markers in murine tumors. selleck chemical Using TCGA data, we verified that DEK expression in primary human breast cancers correlates with the expression of several genes identified by RNA-Seq in our murine model and with M2 macrophage phenotypes. Together, our data demonstrate that by regulating the production of multiple secreted factors, DEK expression in BC cells creates a potentially immune suppressed tumor microenvironment, particularly by inducing M2 tumor associated macrophage (TAM) polarization.The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium-glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included-279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (-0.90%) and weight (-4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (-0.35%) and weight (-2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM.The purpose of this study was to compare the efficacy of botulinum toxin (BoNT) in masseter muscle reduction depending on the amount of chin deviation. Exploring distinctive effects of BoNT relative to the characteristics of facial asymmetry will aid in planning and predicting treatment outcomes. Sixteen adult volunteers were classified into two groups according to the degree of menton deviation observed in posteroanterior cephalograms. Eight had a menton deviation of 3 mm or more and the other eight had less than 3 mm. A total of 25 Units of BoNT was injected into the unilateral masseter muscle of the prominent side for each participant. Changes in the volume and bulkiest height of the lower face on each side were measured with a 3D laser scan at four time points before and 4, 8, and 12 weeks after the injection. Two-way mixed ANOVA was employed for analyses. The volume and bulkiest height of the injected side decreased over time in both types of asymmetry, with significant differences at each time point. The reductions in the volume and bulkiest height were significantly greater in subjects without chin deviation. The reductions in the volume and bulkiest height of the lower face using BoNT are more effective for subjects without chin deviation.Background Bullying is a serious public issue, which mainly occurs in school with negative consequences for the students involved as victims. Very few teacher-delivered interventions have shown positive changes in the victims. The present study aimed at implementing the P.E.A.C.E. (Preparation, Education. Action, Coping, Evaluation) pack program, developed in Australia, in Italian high schools. Method The effectiveness of the program was analyzed through an observational study (pre/post-intervention), involving 551 Italian high school students who completed a questionnaire on bullying victimization, self-efficacy, and bystander behavior. The students were divided into three groups (not involved students, occasional and severe victims) according to their self-reported victimization in the pre-intervention. Results After the intervention, severe victims (victimized once/week or more often) showed a significant decrease in victimization and higher scores in self-efficacy, while an increase in victimization was observed in the not involved students. As reported by all the groups after the intervention, classmates were perceived more likely to intervene when a bullying episode occurred. By contrast, occasional and severe victims perceived their teachers as less likely to intervene. Conclusions The P.E.A.C.E. pack is a promising program confirming in Italian schools the effectiveness already shown in other countries. This program is very useful for severe victims, supporting their self-confidence with a decrease in the frequency of aggressive episodes.Many studies focus on the identification of genomic regions that undergo selective processes, where evidence of selection is revealed and positional candidate genes are identified. The aim of the research was to evaluate the association between positional candidate genes, namely secreted phosphoprotein 1 (SPP1, sheep chromosome Ovis aries OAR6, 36.651-36.658 Mb), protein O-fucosyltransferase 1 (POFUT1, OAR13, 61.006-61.027 Mb) and prolactin receptor (PRLR, OAR16, 38.969-39.028 Mb) with milk yield, composition and coagulation traits. Eight single nucleotide polymorphisms (SNPs) mapping to the three genes were genotyped in 380 Sarda dairy sheep. Statistical analysis revealed an association between SNP rs161844011 at SPP1 (chromosome position Oar_v3 OAR636651870, gene region exon 7) and somatic cell score, while POFUT1 SNP rs424501869 (OAR1361007495, intron 1) was associated with curd firmness both 45 and 60 min after rennet addition (p = 0.015 and p = 0.007, respectively). SNP rs400874750 at PRLR gene (OAR1639004070, intron 2) had a significant association with lactose content (p = 0.