Altered miRNAs Expression Correlates With Gastroenteropancreatic Neuroendocrine Tumors Grades

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors that present a wide spectrum of different clinical and biological characteristics. Currently, tumor grading, determined by Ki-67 staining and mitotic counts, represents the most reliable predictor of prognosis. This time-consuming approach fails to reach high reproducibility standards thus requiring novel approaches to support histological evaluation and prognosis. In this study, starting from a microarray analysis of paraffin-embedded tissue specimens, we defined the miRNAs signature for poorly differentiated NETs (G3) compared to well-differentiated NETs (G1 and G2) consisting of 56 deregulated miRNAs. We identified 8 miRNAs that were expressed in all GEP-NETs grades but at different level. Among these miRNAs, miR-96-5p expression level was progressively higher from grade 1 to grade 3; inversely, its target FoxO1 expression decreased from grade 1 to grade 3. Our results reveal that the miRNAs expression profile of GEP-NET is correlated with the tumor grade, showing a potential advantage of miRNA quantification that could aid clinicians in the classification of common GEP-NETs subtypes. These findings could reliably support the histological evaluation of GEP-NETs paving the way toward personalized treatment approaches

The remarkable influence of N , O -ligands in the assembly of a bis-calix[4]arene-supported [MnIV2MnIII10MnII8] cluster

Calix[4]arenes are versatile ligands, capable of supporting the formation of a wide variety of polymetallic clusters comprising 3d, 4f or 3d-4f metal ions. Calixarene-based metal ion fragments act as both bridging and structure capping moieties in these systems, and this behaviour is systematically extended upon moving to bis-calix[4]arene, a relatively new ligand in which two calix[4]arenes are tethered at the methylene bridge position. N,O-Ligands greatly influence cluster formation with bis-calix[4]arene, affording a remarkable mixed-valence [MnIV2MnIII10MnII8] cluster that displays coordination chemistry typical of each ligand type, but also new structure capping behaviour for the latter.</p

Magneto-structural studies of an unusual [MnIIIMnIIGdIII(OR)4]4− partial cubane from 2,2′-bis-p-tBu-calix[4]arene

Reaction of 2,2'-bis-p-tBu-calix[4]arene (H8L) with MnCl2·4H2O, GdCl3·6H2O and 2,6-pyridinedimethanol (H2pdm) affords [MnIIIMnIIGdIII(H3L)(pdmH)(pdm)(MeOH)2(dmf)]·3MeCN·dmf (3·3MeCN·dmf) upon vapour diffusion of MeCN into the basic dmf/MeOH mother liquor. 3 crystallises in the tetragonal space group P41212 with the asymmetric unit comprising the entire cluster. The highly unusual core contains a triangular arrangement of MnIIIMnIIGdIII ions housed within a [MnIIIMnIIGdIII(OR)4]4- partial cubane. Magnetic susceptibility and magnetisation data reveal best fit parameters JMn(II)-Mn(III) = +0.415 cm-1, JMn(III)-Gd(III) = +0.221 cm-1, JMn(II)-Gd(III) = -0.258 cm-1 and DMn(III) = -4.139 cm-1. Theoretically derived magnetic exchange interactions, anisotropy parameters, and magneto-structural correlations for 3 are in excellent agreement with the experimental data

Dysbiosis Triggers ACF Development in Genetically Predisposed Subjects

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (the Winnie-APCMin/+) combining inflammation and genetics.Methods: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/+ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother's genetics in ACF development, the large intestines of APCMin/+ mice born from wild type mice were investigated by histological analysis at 8 weeks.Results: ACF development in 8-week-old Winnie-APCMin/+mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/+ hosts leads to an increased rate of ACF development.Conclusions: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring

An [Fe^III₃₀] molecular metal oxide

Dearle AE, Cutler DJ, Coletta M, et al. An [FeIII30] molecular metal oxide. Chemical Communications. 2021.Dissolution of FeBr3 in a mixture of acetonitrile and 3,4-lutidine in the presence of an amine results in the formation of an [Fe30] molecular metal oxide containing alternating layers of tetrahedral and octahedral FeIII ions. Mass spectrometry suggests the cluster is formed quickly and remains stable in solution, while magnetic measurements and DFT calculations reveal competing antiferromagnetic exchange interactions

GALAD outperforms aMAP and ALBI for predicting HCC in patients with compensated advanced chronic liver disease: A 12-year prospective study

Background and aims: Surveillance programs are strongly recommended in patients with liver cirrhosis for early detection of HCC development. Six-monthly ultrasound sonography is the most reliable and commonly used technique, especially when associated with serum determination of α-fetoprotein, but different score systems have been proposed to overcome the unsatisfactory diagnostic accuracy of α-fetoprotein. The aim of this 12-year prospective study is to compare the gender, age, AFP-L3, AFP, des-gamma-carboxy prothrombin (GALAD) versus age, gender, bilirubin, albumin, and platelets and albumin-bilirubin scores in predicting HCC onset. Approach and results: A cohort of 545 consecutive patients with compensated advanced chronic liver disease without suspected focal lesions was followed up every 6 months by liver imaging and α-fetoprotein to detect HCC occurrence. Harrell's C-index for censored data was employed to evaluate the performance of any parameters or scores helping to predict HCC development. ROC curve analysis showed that the GALAD score was more accurate in evaluating HCC development than albumin-bilirubin and age, gender, bilirubin, albumin, and platelets. The AUC ranged from 0.7268 to 0.6851 at 5 and 10 years, both in the total cohort and in the sub-cohorts (viral hepatitis, NASH, and alcohol). The HCC Risk model was constructed using univariate and multivariate Cox proportional hazard regression analysis, showing a strong association of GALAD with HR &gt; 1, p &lt; 0.05, in the total and sub-cohorts, and a better risk prediction in the alcohol cohort, both alone and standardized with other blood parameters. Conclusions: GALAD is the most reliable and accurate score system to detect HCC risk of development in patients with compensated advanced chronic liver disease

Effects of Different Biological Therapies on S1/S2 Antibody Response to SARS-CoV-2 Vaccination in a Cohort of Patients with Inflammatory Bowel Disease

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the entire planet. The objectives of our study were to compare responses to the vaccine (Pfizer-Biontech COMIRNATY) in a population of patients with intestinal bowel syndrome undergoing different biological therapies or conventional therapy. The study recruited 390 patients who received the first vaccination dose during the dedicated vaccination campaign for inflammatory bowel disease (IBD) patients. The inclusion criteria were a diagnosis of CD or UC and complete vaccination with the Pfizer-BioNTech COVID-19 (Comirnaty) vaccine. The exclusion criteria were other significant diseases or important therapies under way or contraindications to vaccination according to the European drug surveillance recommendations. Linear rank models were run to assess the association between the different therapies and S1/S2 antibodies at three different times. The models showed that in patients with IBD receiving Vedolizumab a significant increase in mean IgG levels was observed, independently of other therapies and confounding factors (β: 57.45, 95% CI 19.62 to 19.00). This study confirmed the complete antibody response to vaccination against COVID-19 in patients with IBD undergoing biological therapy-particularly Vedolizumab treatment-but also a reduced immune response due to concomitant steroid therapy

Core expansion of bis-calix[4]arene-supported clusters

Stoichiometric control allows for remarkable expansion of the cores of two known bis-calix[4]arene-supported clusters, with concomitant changes to the magnetic properties.</p