Basic Science and Pathogenesis.

Background: Despite being the most common cause of dementia worldwide, the mechanisms underlying the progression of Alzheimer's disease (AD) are not clear and effective treatments are still needed. Hence, further investigation regarding the pathogenesis of AD is required, which might allow for a better understanding of the disease, as well as for an early diagnosis of AD, thus improving the clinical management of AD patients. Here, to identify key proteins in AD pathogenesis, we performed two proteomics strategies, TMT (Tandem Mass Tags) 10-plex quantitative proteomics and LFQ (Label Free Quantification).

'Insufficient'/'Inadequate'/'Non-Diagnostic' Category of the WHO Reporting System for Lung Cytopathology, 2022: A Survey About Use in Practice.

Introduction: The new 'WHO Reporting System for Lung Cytopathology' (2022) includes an 'Insufficient'/'Inadequate'/'Non-diagnostic' category. Although they recommend that each laboratory should choose one term to report this diagnostic category, they do not recommend one term over the others. Our aim was to evaluate the use of these three terms in pulmonary FNACs among Spanish pathologists.

Segmental Regulation of Intestinal Motility by Colitis and the Adaptive Immune System in the Mouse Ileum and Colon.

Gastrointestinal motility disturbances are a hallmark of inflammatory bowel disease (IBD); however, their mechanisms remain unclear. This study used a dextran sulfate sodium-induced colitis mouse model, deficient in mature B and T lymphocytes, to assess intestinal motility and the role of the adaptive immune system in health and IBD. In healthy mice, the absence of adaptive lymphocytes reduced acetylcholine (ACh) sensitivity in the ileum.

Nuclear versus cytoplasmic IKKα signaling in keratinocytes leads to opposite skin phenotypes and inflammatory responses, and a different predisposition to cancer.

IKKα is known as an essential protein for skin homeostasis. However, the lack of suitable models to investigate its functions in the skin has led to IKKα being mistakenly considered as a suppressor of non-melanoma skin cancer (NMSC) development. In this study, using our previously generated transgenic mouse models expressing exogenous IKKα in the cytoplasm (C-IKKα mice) or in the nucleus (N-IKKα mice) of basal keratinocytes, we demonstrate that at each subcellular localization, IKKα differently regulates signaling pathways important for maintaining the balance between keratinocyte proliferation and differentiation, and for the cutaneous inflammatory response.

SIRT1 Mediates the Antagonism of Wnt/β-Catenin Pathway by Vitamin D in Colon Carcinoma Cells.

Cancer initiation and progression result from genetic and epigenetic alterations caused by interactions between environmental and endogenous factors leading to aberrant cell signalling. Colorectal cancers (CRC) are linked to abnormal activation of the Wnt/β-catenin pathway, whose key feature is the nuclear accumulation of acetylated β-catenin in colon epithelial cells. Nuclear β-catenin acts as a transcriptional co-activator, targeting genes involved in cell proliferation and invasion.