Clinical and biological significance of miR-23b and miR-193a in human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common cancer of the liver with a very poor prognosis. The dysregulation of microRNAs (miRs) is indeed implicated in HCC onset and progression. In this study, we have evaluated the expression of miR-23b and miR-193a in a large cohort of 59 and 67 HCC patients, respectively. miR-23b and miR-193a resulted significantly down-regulated in primary HCCs compared to their matched peritumoral counterparts. Furthermore, patients with higher miR-193a expression exhibited longer OS and DFS, suggesting that miR-193a may be a molecular prognostic factor for HCC patients. Since the regulation of miRs by DNA methylation may occur in human cancers, we verified whether the down-modulation of miR-23b and miR-193a in HCC tissues could be related to DNA methylation. An inverse trend between miR-23b expression and DNA methylation was observed, indicating that miR-23b can be epigenetically regulated. By contrast, the down-regulation of miR-193a was not mediated by DNA methylation. To verify the potential role of miR-23b and miR-193a as responsive molecular targets in vitro, we used the inhibitor of DNA methylation 5-aza-dC to restore miR-23b expression level in combination with miR-193a transfection. The combined treatment led to a significant inhibition of cellular proliferation and migration. Taken together, our findings provide evidence that miR-23b and miR-193a may be molecular diagnostic and prognostic factors for HCC; furthermore, miR-23b and miR-193a are responsive molecular targets for limiting HCC cell aggressiveness in combination with the epigenetic drug 5-aza-dC. Moreover, our results provide new advances in the epigenetic regulation of these miRs in HCC

On the β-detection efficiency of a combined Si and plastic stack detector for DESPEC

A Geant4 simulation has been carried out in order to determine the B-detection efficiency of a rare isotope beam implantation setup, for decay spectroscopy experiments, comprising a number of Double Sided Silicon Strip Detectors (DSSSDs) and two plastic scintillation detectors placed upstream and downstream. The absolute efficiency for the emitted B-particle detection from radioactive fragments implanted in the DSSSDs using fast-timing plastic-scintillator detector, is calculated. The detection efficiency of the setup has been studied with two different distances between the Si layers and plastics. The requirement for the thickness of the Si detector layers and its implication on the B-detection effciency has been investigated for 1 mm and 300 um thickness of Si layers. The combined efficiency of DSSSD and plastic detectors were also simulated for two different thicknesses of the DSSSD

Tecnologie Digitali e DSA

Il termine “strumento compensativo”, concetto essenziale nel percorso educativo degli studenti con DSA, è spesso fonte di dubbio per genitori, insegnanti e ragazzi: quali sono gli strumenti compensativi digitali presenti sul mercato? Uno strumento vale l’altro? Come si fa a scegliere quello giusto? Per contribuire a rispondere a queste domande è stata redatta una “rassegna ragionata” di 233 tecnologie digitali, raccogliendo informazioni sugli strumenti utilizzati da docenti, esperti, genitori e studenti con DSA. La rassegna offre un aiuto per orientarsi tra le varie opportunità e attuare una scelta consapevole delle tecnologie compensative a supporto dell’apprendimento e dello studio autonomo

Effect of comorbidities on survival in patients > 80 years of age at onset of renal replacement therapy: data from the ERA-EDTA Registry

Background. The number of elderly patients on renal replacement therapy (RRT) is increasing. The survival and quality of life of these patients may be lower if they have multiple comorbidities at the onset of RRT. The aim of this study was to explore whether the effect of comorbidities on survival is similar in elderly RRT patients compared with younger ones. Methods. Included were 9333 patients >= 80years of age and 48352 patients 20-79 years of age starting RRT between 2010 and 2015 from 15 national or regional registries submitting data to the European Renal Association-European Dialysis and Transplantation Association Registry. Patients were followed until death or the end of 2016. Survival was assessed by Kaplan-Meier curves and the relative risk of death associated with comorbidities was assessed by Cox regression analysis. Results. Patients >= 80years of age had a greater comorbidity burden than younger patients. However, relative risks of death associated with all studied comorbidities (diabetes, ischaemic heart disease, chronic heart failure, cerebrovascular disease, peripheral vascular disease and malignancy) were significantly lower in elderly patients compared with younger patients. Also, the increase in absolute mortality rates associated with an increasing number of comorbidities was smaller in elderly patients. Conclusions. Comorbidities are common in elderly patients who enter RRT, but the risk of death associated with comorbidities is less than in younger patients. This should be taken into account when assessing the prognosis of elderly RRT patients.Peer reviewe

Preventive acetaminophen reduces postoperative opioid consumption, vomiting, and pain scores after surgery: systematic review and meta-analysis

Background and Objectives: Preventive analgesia has been proposed as a potential strategy to reduce postoperative pain. However, there is currently no review that focuses on acetaminophen for preventive analgesia. Methods: We conducted a search of MEDLINE, EMBASE, Cinahl, AMED, and CENTRAL databases identifying randomized controlled trials that compared preventive acetaminophen with postincision acetaminophen. Results: Seven studies with 544 participants were included. Overall, the studies showed a reduction in 24-hour opioid consumption (standardized mean difference [SMD] of -0.52; 95% confidence interval [95% CI], -0.98 to -0.06), lower pain scores at 1 hour (MD, -0.50; 95% CI, -0.98 to -0.02) and 2 hours (MD, -0.34; 95% CI, -0.67 to -0.01), and a lower incidence of postoperative vomiting (risk ratio, 0.50; 95% CI, 0.31-0.83) in the preventive acetaminophen group. Current studies are limited by a potential risk of bias. Conclusions: To our knowledge, this is the first review to describe a potential preventive effect of acetaminophen. However, well-conducted randomized controlled trials are necessary to substantiate the conclusions of this review

Novel Roles for Hypoxia and Prostaglandin E2 in the Regulation of IL-8 During Endometrial Repair

The endometrium has a remarkable capacity for efficient repair; however, factors involved remain undefined. Premenstrual progesterone withdrawal leads to increased prostaglandin (PG) production and local hypoxia. Here we determined human endometrial expression of interleukin-8 (IL-8) and the roles of PGE2 and hypoxia in its regulation. Endometrial biopsy specimens (n = 51) were collected. Endometrial cells and explants were exposed to 100 nmol/L of PGE2 or 0.5% O2. The endometrial IL-8 concentration peaked during menstruation (P < 0.001) and had a significant proangiogenic effect. IL-8 was increased by PGE2 and hypoxia in secretory but not proliferative explants, which suggests that exposure to progesterone is essential. In vitro progesterone withdrawal induced significant IL-8 up-regulation in proliferative explants primed with progestins, but only in the presence of hypoxia. Epithelial cells treated simultaneously with PGE2 and hypoxia demonstrated synergistic increases in IL-8. Inhibition of HIF-1 by short hairpin RNA abolished hypoxic IL-8 induction, and inhibition of NF-κB by an adenoviral dominant negative inhibitor decreased PGE2-induced IL-8 expression (P > 0.05). Increased menstrual IL-8 is consistent with a role in repair. Progesterone withdrawal, hypoxia, and PGE2 regulate endometrial IL-8 by acting via HIF-1 and NF-κB. Hence, progesterone withdrawal may activate two distinct pathways to initiate endometrial repair

Prokineticin 1 modulates IL-8 expression via the calcineurin/NFAT signaling pathway

AbstractProkineticins and their receptors are expressed in various cellular compartments in human endometrium, with prokineticin 1 (PROK1) showing a dynamic pattern of expression across the menstrual cycle and during pregnancy. Previous studies suggest that PROK1 can play an important role in implantation and early pregnancy by inducing vascular remodeling and increasing vascular permeability. Here we demonstrate that PROK1 induces the expression of IL-8, a chemokine with angiogenic properties, in endometrial epithelial Ishikawa cells stably expressing prokineticin receptor 1 and in human first trimester decidua. We also show that IL-8 promoter activity is induced by PROK1 and that this requires the presence of AP1 and NFAT motifs. The role of calcineurin/NFAT signaling pathway is confirmed by the use of specific chemical inhibitors. Additionally, PROK1 induces the expression of the regulator of calcineurin 1 isoform 4 (RCAN1-4) via the calcineurin/NFAT pathway. A modulatory role for RCAN1-4 is demonstrated by RCAN1-4 overexpression which results in the inhibition of PROK1-induced IL-8 expression whereas reduction in RCAN1-4 endogenous expression results in an increase in PROK1-induced IL-8 production. Our findings show that in endometrial cells PROK1 can activate the calcineurin/NFAT pathway to induce IL-8 expression and that this is negatively modulated by the induction of expression of RCAN1-4