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microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumoral tissues from surgical specimens of CRC patients. KRAS mutations were detected in 11 tumoral samples. In a first analysis, we found 5 miRNAs (miR-215-5p, miR-9-5p, miR-138-5p, miR378a-3p, and miR-150-5p) that were significantly downregulated and one upregulated (miR-135b-5p) in tumoral tissues compared with the peritumoral tissues. Furthermore, by comparing miRNA profile between KRAS mutated CRC tissues respect to wild type CRC tissues, we found 7 miRNA (miR-27b-3p, miR-191-5p, miR-let7d-5p, miR-15b-5p, miR-98-5p, miR-10a-5p, and miR-149-5p) downregulated in KRAS mutated condition. In conclusion, we have identified a panel of miRNAs that specifically distinguish CRC tissues from peritumoral tissue and a different set of miRNAs specific for CRC with KRAS mutations. These findings may contribute to the discovering of new molecular biomarkers with clinic relevance and might shed light on novel molecular aspects of CRC. [ABSTRACT FROM AUTHOR]

Chronic inflammatory bowel diseases (IBDs) are a subject of great interest in gastroenterology, due to a pathological mechanism that is difficult to explain and an optimal therapeutic approach still undiscovered. Crohn's disease (CD) is one of the main entities in IBD, characterized by clinical polymorphism and great variability in the treatment response. Modern theories on the pathogenesis of CD have proven that gut microbiome and environmental factors lead to an abnormal immune response in a genetically predisposed patient. Genome-wide association studies in patients with CD worldwide revealed several genetic mutations that increase the risk of IBD and that predispose to a more severe course of disease. Gut microbiota is considered a compulsory and an essential part in the pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different bacterial strains can be found in all patients with IBD. The discovery of Escherichia coli entero-invasive on resection pieces in patients with CD now increases the likelihood of antimicrobial or vaccine-type treatments. Recent studies targeting intestinal immunology and its molecular activation pathways provide new possibilities for therapeutics. In addition to antitumor necrosis factor molecules, which were a breakthrough in IBD, improving mucosal healing and resection-free survival rate, other classes of therapeutic agents come to focus. Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent cellular immune response. In addition to anti-integrin antibodies, chemokine receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging results in clinical trials. Micro-RNAs have demonstrated their role as disease biomarkers but it could also become useful for the treatment of IBD. Moreover, cellular therapy is another therapeutic approach under development, aimed for severe refractory CD. Other experimental treatments include intravenous immunoglobulins, exclusive enteral nutrition, and granulocyte colony-stimulating factors. [ABSTRACT FROM AUTHOR]

Intestinal strictures are an important complication of Crohn's disease (CD), with ~40% of patients developing symptomatic obstruction within 10 years of diagnosis. However, there is a paucity of research examining the mechanisms driving the development of fibrotic strictures in CD. The present study aimed to identify the mucosal markers associated with stricturing complications by examining the differences in the gene expression profiles of two patient cohorts: Patients diagnosed with inflammatory CD (n=12) and patients with stricturing CD (n=9). For each patient, a paired sample of inflamed and uninflamed mucosa was isolated and assessed by quantitative PCR using a large panel of genes associated with inflammatory bowel disease. The presents study revealed a significantly increased level of four genes in the mucosa of patients with strictures compared with the inflammatory pattern of the disease: Formyl-peptide receptor 1 [P=0.019; fold change (FC)=11.6], C-C chemokine receptor type 1 (P=0.035; FC=5.44), IFN-γ-inducible protein 10 (P=0.037; FC=3.8) and C-C chemokine ligand 25 (P=0.048; FC=3.56). The augmented expression of these four genes in the CD stricturing phenotype, if confirmed in larger cohorts of patients, could help elucidate the mechanisms leading to disease-associated complications. [ABSTRACT FROM AUTHOR]

Background & Aims: Colorectal cancer (CRC) is the third cause of cancer-related death worldwide. Screening programs can reduce CRC mortality rates by up to 60%. In line with the European Union recommendations, Romania started the first four regional pilot screening programs in 2020 (the ROCCAS II projects). This study reports the interim screening performance indicators. Methods: People aged 50 to 74 years were invited to the screening program. General practitioners (GPs) evaluated CRC risk based on a survey. High-risk or symptomatic individuals were referred directly to colonoscopy. The average risk participants received a fecal immunochemical test (FIT). Positive cases were invited to colonoscopy. Three regions were screened using the OC-SENSOR® (South-Muntenia, Bucharest-Ilfov, South-East) and one region (South-West) used the FOB GOLD®. The data was collected in the ROCCAS screening electronic registry. The following FIT parameters were evaluated: rates of return, invalidity, positivity, and colonoscopy acceptance rate according to age group, gender, region of provenience, and vulnerability status. Results: We included all cases screened between January 1, 2022 and September 30, 2023. In total, 168,958 people received the FIT test within the projects. The global FIT return rate was 90%. Factors associated with a higher return rate were female gender (90.77% vs 88.83%, p<0.0001), vulnerable status (91.23% vs 88.83%; p<0.00001), and rural residence (91.84% vs 88.42%, p<0.00001). The overall positivity rate was 5.75%. It was higher in males (7.64% vs 4.57% in females, p<0.00001) and progressively increased with the age group. The total invalid FIT rate was 5.87%, significantly lower for OC-SENSOR® (2.24%) than for the FOB GOLD® (13.6%). The overall acceptability rate for colonoscopy was 51.3%. Conclusions: According to our preliminary data, GP's participation in the pilot programs ensured adequate adherence to screening through FIT. The rate for FIT return and positivity were acceptable for both tests, while the invalid rate was much higher in FOB GOLD® compared to the OC-SENSOR®. Moreover, colonoscopy acceptance needs to be improved. Our preliminary analysis revealed the screening performance indicators meet the EU recommendations and fulfill the premises for national-level expansion of the program starting in 2024. [ABSTRACT FROM AUTHOR]