Colorectal cancer development is affected by the ECM molecule EMILIN-2 hinging on macrophage polarization via the TLR-4/MyD88 pathway

Background Colorectal cancer is one of the most frequent and deadly tumors. Among the key regulators of CRC growth and progression, the microenvironment has emerged as a crucial player and as a possible route for the development of new therapeutic opportunities. More specifically, the extracellular matrix acts directly on cancer cells and indirectly affecting the behavior of stromal and inflammatory cells, as well as the bioavailability of growth factors. Among the ECM molecules, EMILIN-2 is frequently down-regulated by methylation in CRC and the purpose of this study was to verify the impact of EMILIN-2 loss in CRC development and its possible value as a prognostic biomarker. Methods The AOM/DSS CRC protocol was applied to Emilin-2 null and wild type mice. Tumor development was monitored by endoscopy, the molecular analyses performed by IHC, IF and WB and the immune subpopulations characterized by flow cytometry. Ex vivo cultures of monocyte/macrophages from the murine models were used to verify the molecular pathways. Publicly available datasets were exploited to determine the CRC patients' expression profile; Spearman's correlation analyses and Cox regression were applied to evaluate the association with the inflammatory response; the clinical outcome was predicted by Kaplan-Meier survival curves. Pearson correlation analyses were also applied to a cohort of patients enrolled in our Institute. Results In preclinical settings, loss of EMILIN-2 associated with an increased number of tumor lesions upon AOM/DSS treatment. In addition, in the early stages of the disease, the Emilin-2 knockout mice displayed a myeloid-derived suppressor cells-rich infiltrate. Instead, in the late stages, lack of EMILIN-2 associated with a decreased number of M1 macrophages, resulting in a higher percentage of the tumor-promoting M2 macrophages. Mechanistically, EMILIN-2 triggered the activation of the Toll-like Receptor 4/MyD88/NF-kappa B pathway, instrumental for the polarization of macrophages towards the M1 phenotype. Accordingly, dataset and immunofluorescence analyses indicated that low EMILIN-2 expression levels correlated with an increased M2/M1 ratio and with poor CRC patients' prognosis. Conclusions These novel results indicate that EMILIN-2 is a key regulator of the tumor-associated inflammatory environment and may represent a promising prognostic biomarker for CRC patients

PRA Melting-ICE Project: Svalbard 2022 Expeditions Report

Arctic regions are among the fastest warming areas of the planet. Increasing average temperatures over the last five decades have deepened the thawing of the upper-most layer of permafrost across the Arctic, which contains significant amounts of organic carbon. The progressive deepening of seasonal thawing releases carbon that is used by active microorganisms which also produce greenhouse gases, potentially onsetting a positive feedback on global warming. Despite their importance in controlling organic matter degradation and greenhouse gas fluxes to the atmosphere, there is a lack of data on activity and dynamics of microbial communities in High Arctic soils in response to seasonal thaw. This report describes three specific expeditions performed on the Svalbard archipelago, carried out within the framework of the PRA (Italian Arctic Research Program) project Melting-ICE, performed between February and October 2022, reporting site characteristics and samples collected. The project aims to investigate the diversity and activity of active layer microbial communities across a full season thaw cycle, correlating microbial diversity with gas fluxes and composition. During these expeditions, a total of eight different sites were selected to investigate the microbiology and geochemistry of soils, as well as to estimate the gas fluxes from the soil to the atmosphere. The data collected in the field, combined with the results obtained in the laboratory, will provide a snapshot of the seasonal activity of the microbial communities present in the permafrost’s active layer. The three campaigns will provide data to estimate the impact of permafrost melting on the carbon cycle and the role of microorganisms in the release of greenhouse gases

Colorectal cancer development is affected by the ECM molecule EMILIN-2 hinging on macrophage polarization via the TLR-4/MyD88 pathway

Abstract Background Colorectal cancer is one of the most frequent and deadly tumors. Among the key regulators of CRC growth and progression, the microenvironment has emerged as a crucial player and as a possible route for the development of new therapeutic opportunities. More specifically, the extracellular matrix acts directly on cancer cells and indirectly affecting the behavior of stromal and inflammatory cells, as well as the bioavailability of growth factors. Among the ECM molecules, EMILIN-2 is frequently down-regulated by methylation in CRC and the purpose of this study was to verify the impact of EMILIN-2 loss in CRC development and its possible value as a prognostic biomarker. Methods The AOM/DSS CRC protocol was applied to Emilin-2 null and wild type mice. Tumor development was monitored by endoscopy, the molecular analyses performed by IHC, IF and WB and the immune subpopulations characterized by flow cytometry. Ex vivo cultures of monocyte/macrophages from the murine models were used to verify the molecular pathways. Publicly available datasets were exploited to determine the CRC patients’ expression profile; Spearman’s correlation analyses and Cox regression were applied to evaluate the association with the inflammatory response; the clinical outcome was predicted by Kaplan-Meier survival curves. Pearson correlation analyses were also applied to a cohort of patients enrolled in our Institute. Results In preclinical settings, loss of EMILIN-2 associated with an increased number of tumor lesions upon AOM/DSS treatment. In addition, in the early stages of the disease, the Emilin-2 knockout mice displayed a myeloid-derived suppressor cells-rich infiltrate. Instead, in the late stages, lack of EMILIN-2 associated with a decreased number of M1 macrophages, resulting in a higher percentage of the tumor-promoting M2 macrophages. Mechanistically, EMILIN-2 triggered the activation of the Toll-like Receptor 4/MyD88/NF-κB pathway, instrumental for the polarization of macrophages towards the M1 phenotype. Accordingly, dataset and immunofluorescence analyses indicated that low EMILIN-2 expression levels correlated with an increased M2/M1 ratio and with poor CRC patients’ prognosis. Conclusions These novel results indicate that EMILIN-2 is a key regulator of the tumor-associated inflammatory environment and may represent a promising prognostic biomarker for CRC patients. </jats:sec

Efficacy of novel endoscopic hemostatic agent for bleeding control and prevention: Results from a prospective, multicenter national registry

: Background and study aims Topical hemostatic agents emerged as a new treatment modality for gastrointestinal bleeding. The aim of this study was to assess the safety and efficacy of PuraStat for control of active bleeding and for prevention of bleeding after different operative endoscopy procedures. Patients and methods A national, multicenter, observational registry was established to collect data from ten Italian centers from June 2021 to February 2023. Demographics, type of application (active gastrointestinal bleeding or prevention after endoscopic procedures, site, amount of gel used, completeness of coverage of the treated area), outcomes (rates of intraprocedural hemostasis and bleeding events during 30-day follow-up), and adverse events (AEs) were prospectively analyzed. Results Four hundred and one patients were treated for active gastrointestinal bleeding or as a preventive measure after different types of operative endoscopy procedures. Ninety-one treatments for active bleeding and 310 preventive applications were included. In 174 of 401 cases (43.4%), PuraStat was the primary treatment modality. Complete coverage was possible in 330 of 401 (82.3%) with difficulty in application in seven of 401 cases (1.7%). Hemostasis of active bleedings was achieved in 90 of 91 patients (98.9%). In 30-day follow-up 3.9% patients in whom PuraStat was used for prophylaxis had a bleeding event compared with 7.7% after hemostasis. No AEs related to the use of PuraStat were reported. Conclusions PuraStat is a safe and effective hemostat both for bleeding control and for bleeding prevention after different operative endoscopy procedures. Our results suggest that the possible applications for the use of PuraStat may be wider compared with current indications

A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy

An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors

Additional file 2 of Colorectal cancer development is affected by the ECM molecule EMILIN-2 hinging on macrophage polarization via the TLR-4/MyD88 pathway

Additional file 2: Table S2

Additional file 3 of Colorectal cancer development is affected by the ECM molecule EMILIN-2 hinging on macrophage polarization via the TLR-4/MyD88 pathway

Additional file 3: Figure S1-Figure S3