👤 Jorge Mercado

Identifying proteomic signatures in treatment-naïve individuals newly diagnosed with inflammatory bowel disease (IBD) may provide insights into the underlying pathophysiological mechanisms of the disease and aid in distinguishing Crohn's disease (CD) from ulcerative colitis (UC). In the discovery phase, label-free quantitative proteomics was performed to analyze proteomic profiles in serum extracellular vesicles (EVs), serum, urine, and intestinal tissue from 100 newly diagnosed IBD patients (50 CD and 50 UC), and 51 healthy controls (HC). Serum candidate biomarkers were validated using ELISA in a separate subset cohort (87 CD, 134 UC, and 99 HC), and immunohistochemistry was performed on biopsies from the discovery cohort to confirm findings. We identified 419 proteins in serum EVs, 468 in serum, 683 in urine, and 2603 in intestinal tissue. ELISA results showed lower levels of TTR and APOC3 and higher levels of ATRN in UC patients compared to HC. Similarly, CD patients showed lower TTR and higher ATRN levels compared to HC. Moreover, serum protein S10A9 was differentially upregulated in CD vs UC. Immunohistochemistry revealed increased PRDX4 and AZU1 expression in the ileum of CD patients, whereas AOFB expression was lower in the ileum of CD and in the left colon of both CD and UC compared to HC. This comprehensive proteomic study has identified a set of proteins differentially expressed in IBD, which may contribute to a better understanding of its mechanisms and hold promise as candidate biomarkers. Although these findings are preliminary, they warrant further investigation to evaluate their diagnostic and therapeutic relevance. Show less

GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion. Show less

Lipopolysaccharide binding proteins (LBPs) and bactericidal permeability increasing proteins (BPIs) play significant roles in the immune response of vertebrates against bacterial pathogens. These soluble proteins produced by immune cells, specifically interact with and bind to bacterial lipopolysaccharides (LPS), with BPIs also displaying antibacterial activity. In Argopecten purpuratus scallop larvae resistant to Vibrio bivalvicida VPAP30, we identified a significant overexpression of a transcript displaying molecular features of an LBP/BPI protein, both before and after infection. Therefore, in the present work we aimed to understand the role of this novel LBP/BPI, named ApLBP/BPI3, in the scallop resistance to this Vibrio. The ApLBP/BPI3 open reading frame encodes a putative protein of 506 amino acids, with a molecular weight 56.78 kDa. The protein contains a C-terminal domain of 403-amino acid that, after theorical cleavage, displays a soluble form of 44.99 kDa, featuring two BPI/LBP/CETP domains, an apolar binding pocket, a single disulfide bond and a BPI dimerization interface. Phylogenetic analysis reveals high similarity between ApLBP/BPI3 and other mollusk LBP/BPI proteins. Aplbp/bpi3 transcripts were constitutively and highly expressed in hemocytes, gills, mantle, and digestive gland tissues, and were induced following VPAP30 infection in scallop larvae and adult hemocytes. We characterized ApLBP/BPI3 protein using a polyclonal antibody against a synthetic peptide. ApLBP/BPI3 was secreted to the media by infected cultured hemocytes, detected by ELISA. ApLBP/BPI3 was spotted inside non-infected hemocytes, bound to the cell wall of V. bivalvicida after in vitro hemocyte infection, and coating the gills and mantle epithelial barriers before and after an in vivo immune challenge, with stronger detection after VPAP30 injection, detected by immunofluorescence. Infected scallop larvae showed increased ApLBP/BPI3 levels, with slightly higher production in resistant larvae, determined by Western blot. Finally, silencing the Aplbp/bpi3 transcript through RNA interference and and subsequently infecting scallop juveniles with an LD50 of V. bivalvicida resulted in 100 % mortality. Altogether, results demonstrate the essential role of this immune effector in the resistance of A. purpuratus. Show less