RAGE inhibition blunts insulin-induced oncogenic signals in breast cancer.

The receptor for advanced glycation end products (RAGE) is implicated in diabetes and obesity complications, as well as in breast cancer (BC). Herein, we evaluated whether RAGE contributes to the oncogenic actions of Insulin, which plays a key role in BC progression particularly in obese and diabetic patients. Analysis of the publicly available METABRIC study, which collects gene expression and clinical data from a large cohort (n = 1904) of BC patients, revealed that RAGE and the Insulin Receptor (IR) are co-expressed and associated with negative prognostic parameters. In MCF-7, ZR75 and 4T1 BC cells, as well as in patient-derived Cancer-Associated Fibroblasts, the pharmacological inhibition of RAGE as well as its genetic depletion interfered with Insulin-induced activation of the oncogenic pathway IR/IRS1/AKT/CD1. Mechanistically, IR and RAGE directly interacted upon Insulin stimulation, as shown by in situ proximity ligation assays and coimmunoprecipitation studies. Of note, RAGE inhibition halted the activation of both IR and insulin like growth factor 1 receptor (IGF-1R), as demonstrated in MCF-7 cells KO for the IR and the IGF-1R gene via CRISPR-cas9 technology. An unbiased label-free proteomic analysis uncovered proteins and predicted pathways affected by RAGE inhibition in Insulin-stimulated BC cells. Biologically, RAGE inhibition reduced cell proliferation, migration, and patient-derived mammosphere formation triggered by Insulin. In vivo, the pharmacological inhibition of RAGE halted Insulin-induced tumor growth, without affecting blood glucose homeostasis. Together, our findings suggest that targeting RAGE may represent an appealing opportunity to blunt Insulin-induced oncogenic signaling in BC.

Endoparasites of the European Hare (Lepus Europaeus) (Pallas, 1778) in Central Italy.

Brown hare (Lepus europaeus) populations in Europe have declined through decades due to several, but not clear yet, factors. Parasite infections and diseases are some of the causes that directly affected the survival and breeding rates of animal population. A study on the endoparasites of 70 hares (37 hunted free-living hares, and 33 bred on farms hares) was performed between 2015 - 2017 in the province of Grosseto (central Italy), an area where the impact of parasites in the hare population has never been investigated. During necroscopic analysis of hunted hares the following helminthes were found: Trichostrongylus retortaeformis (87.1 %), Passalurus ambiguus (12.9 %) and Andrya spp. (6.4 %) in the intestinal tract, Protostrongylus cuniculorum (8.3 %) in lungs and Dicrocoelium dendriticum (16.7 %) in livers. The prevalences of the intestinal helminthes in bred hares were: 12.1 % for Passalurus ambiguus and 3 % for Trichostrongylus retortaeformis. The coprological analysis showed prevalences of 64.9 % for coccidia in the 37 hunted hares and 45.5 % in the 33 bred hares. The relationship between the intensities of parasitic infections and body weight was evaluated. The results of the present study in the Grosseto area indicate that free-living hares have few species of parasites and that the intensities of parasitic infection did not affect their general condition and health, suggesting that endoparasites played no detectable role in the dynamics of this hare population.

Performance characteristics of five antigen-detecting rapid diagnostic test (Ag-RDT) for SARS-CoV-2 asymptomatic infection: a head-to-head benchmark comparison.

BACKGROUND: Mass testing for early identification and isolation of infectious COVID-19 individuals is efficacious for reducing disease spread. Antigen-detecting rapid diagnostic tests (Ag-RDT) may be suitable for testing strategies; however, benchmark comparisons are scarce. METHODS: We used 286 nasopharyngeal specimens from unexposed asymptomatic individuals collected between December 2020 and January 2021 to assess five Ag-RDTs marketed by Abbott, Siemens, Roche Diagnostics, Lepu Medical, and Surescreen. RESULTS: For the overall sample, the performance parameters of Ag-RDTs were as follows: Abbott assay, sensitivity 38.6% (95%CI 29.1-48.8) and specificity 99.5% (97-100%); Siemens, sensitivity 51.5% (41.3-61.6) and specificity 98.4% (95.3-99.6); Roche, sensitivity 43.6% (33.7-53.8) and specificity 96.2% (92.4-98.5); Lepu, sensitivity 45.5% (35.6-55.8) and specificity 89.2% (83.8-93.3%); Surescreen, sensitivity 28.8% (20.2-38.6) and specificity 97.8% (94.5-99.4%). For specimens with cycle threshold (Ct) <30 in RT-qPCR, all Ag-RDT achieved a sensitivity ≥70%. The modelled negative- and positive-predictive value for 1% prevalence were >99% and <50%, respectively. CONCLUSIONS: When screening unexposed asymptomatic individuals, two Ag-RDTs achieved sensitivity ≥80% for specimens with Ct<30 and specificity ≥96%. The estimated negative predictive value suggests the suitability of Ag-RDTs for mass screenings of SARS-CoV-2 infection in the general population.