Sphingomyelin Metabolism Modifies Luminal A Breast Cancer Cell Line under a High Dose of Vitamin C.

The role of sphingomyelin metabolism and vitamin C in cancer has been widely described with conflicting results ranging from a total absence of effect to possible preventive and/or protective effects. The aim of this study was to establish the possible involvement of sphingomyelin metabolism in the changes induced by vitamin C in breast cancer cells. The MCF7 cell line reproducing luminal A breast cancer and the MDA-MB-231 cell line reproducing triple-negative breast cancer were used. Cell phenotype was tested by estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 expression, and proliferation index percentage. Sphingomyelin was localized by an EGFP-NT-Lys fluorescent probe. Sphingomyelin metabolism was analyzed by RT-PCR, Western blotting and UFLC-MS/MS. The results showed that a high dose of vitamin C produced reduced cell viability, modulated cell cycle related genes, and changed the cell phenotype with estrogen receptor downregulation in MCF7 cell. In these cells, the catabolism of sphingomyelin was promoted with a large increase in ceramide content. No changes in viability and molecular expression were observed in MB231 cells. In conclusion, a high dose of vitamin C induces changes in the luminal A cell line involving sphingomyelin metabolism.

The development of artificial intelligence in the histological diagnosis of Inflammatory Bowel Disease (IBD-AI).

BACKGROUND: Inflammatory bowel disease (IBD) includes Crohn's Disease (CD) and Ulcerative Colitis (UC). Correct diagnosis requires the identification of precise morphological features such basal plasmacytosis. However, histopathological interpretation can be challenging, and it is subject to high variability. AIM: The IBD-Artificial Intelligence (AI) project aims at the development of an AI-based evaluation system to support the diagnosis of IBD, semi-automatically quantifying basal plasmacytosis. METHODS: A deep learning model was trained to detect and quantify plasma cells on a public dataset of 4981 annotated images. The model was then tested on an external validation cohort of 356 intestinal biopsies of CD, UC and healthy controls. AI diagnostic performance was calculated compared to human gold standard. RESULTS: The system correctly found that CD and UC samples had a greater prevalence of basal plasma cells with mean number of PCs within ROIs of 38.22 (95 % CI: 31.73, 49.04) for CD, 55.16 (46.57, 65.93) for UC, and 17.25 (CI: 12.17, 27.05) for controls. Overall, OR=4.968 (CI: 1.835, 14.638) was found for IBD compared to normal mucosa (CD: +59 %; UC: +129 %). Additionally, as expected, UC samples were found to have more plasma cells in colon than CD cases. CONCLUSION: Our model accurately replicated human assessment of basal plasmacytosis, underscoring the value of AI models as a potential aid IBD diagnosis.

Claudin-2: A marker for a better evaluation of histological mucosal healing in inflammatory bowel diseases.

BACKGROUND: Histological mucosal healing has become a paramount target goal to achieve in the treatment of inflammatory bowel diseases. However, there is still a lack of agreement on the best way to reach this goal, since numerous histological scores are available worldwide. AIMS: We investigated whether claudin-2, a member of claudin family involved in the regulation of intestinal tight junctions, might be useful to assess the presence of active disease in patients with inflammatory bowel diseases. METHODS: Biopsies from 123 patients with ulcerative colitis, Crohn's disease, infectious colitides and irritable bowel syndrome patients where tested with immunohistochemistry for claudin-2. RESULTS: Claudin-2 appeared to be a very sensitive marker of disease activity in inflammatory bowel diseases, but was negative in the other kinds of patients. In addition, immunohistochemistry for claudin-2 showed good reproducibility by different pathologists. CONCLUSIONS: Should these findings be confirmed in more numerous cohorts of patients, and especially in those with minimal or focal residual disease activity, this simple assessment could be useful in the routine daily practice to facilitate the task of pathologists and clinicians in the diagnosis and management of patients with inflammatory bowel diseases.