Background/Objectives: Inflammatory bowel diseases (IBD), including mainly ulcerative colitis (UC) and Crohn’s disease (CD), have been associated with cognitive and psychological changes, though the mechanisms remain unclear. Methods: This prospective case-control study aimed to evaluate cognitive performance and biomarkers (homocysteine, serum amyloid A, brain-derived neurotrophic factor, and S100B protein) in IBD patients. Results: A total of 90 individuals (34 UC, 21 CD, and 35 controls) were assessed using the Montreal Cognitive Assessment (MoCA), the Memory Impairment Index (MIS), and biomarker analysis. MoCA and MIS testing showed significant differences between UC, CD, and the controls, with lower scores observed in IBD groups (p = 0.003, p = 0.015). Regarding trail-making tests, digit symbol substitution tests, and forward and backward digit spans, no significant changes were observed. No functional deficits were observed in daily activities. Biomarker analysis revealed lower brain-derived neurotrophic factor and higher serum amyloid A levels in IBD patients, correlated to MOCA and MIS scores. There were no significant differences in psychological distress between IBD patients and the controls. Subtle cognitive declines were noted across all groups during the 1-year follow-up, without any statistical significance when groups were compared. Conclusions: In conclusion, IBD patients reported lower cognitive scores compared to the controls, while no differences in depression and anxiety scores were observed. Higher BDNF levels correlated with better cognitive functioning, while higher serum amyloid A correlated with lower cognitive functioning.

Background: This research aimed to compare the traditional in-solution digestion (inSol) and solid-phase-enhanced sample preparation (SP3) methods for salivary proteomics, with a focus on identifying mucopolysaccharidosis (MPS)-relevant proteins. Methods: Saliva samples were processed under multiple analytical conditions, including two precipitation methods (methanol or incubation with trichloroacetic acid), paired with either Rapigest or 8M urea/2M thiourea (UT) solubilization buffers. Additionally, the SP3 method was directly applied to raw saliva without pre-processing. Proteome coverage, reproducibility, digestion efficiency, and gene function were assessed. Results: The inSol method consistently provided superior proteome coverage, with trichloroacetic acid precipitation and Rapigest buffer yielding 74 MPS-relevant proteins, compared to 40 with SP3 MeOH UT. Both methods showed high digestion efficiency, particularly with Rapigest buffer, achieving over 80% full cleavage across conditions. Functional analysis revealed broad similarities, with protocol-specific impacts on protein classes and cellular components. Conclusions: This study is the first to compare SP3 and in-solution digestion for salivary proteomics, emphasizing the importance of method selection to address matrix-specific challenges. The results highlight the robustness of inSol for comprehensive proteome profiling and SP3′s potential for streamlined clinical workflows, offering valuable insights into optimizing salivary proteomics for biomarker discovery in MPS and other diseases.

Background/Objectives: Mass-forming chronic pancreatitis (MFP) and pancreatic ductal adenocarcinoma (PDAC) can present with overlapping radiological, clinical, and serological features in patients with underlying chronic pancreatitis (CP), making differential diagnosis particularly challenging. Current diagnostic tools, including CA19-9 and endoscopic ultrasound (EUS) imaging, often lack the specificity needed to reliably distinguish between these conditions. The objective of this study was to investigate whether the proteomic profiling of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples could provide molecular-level discrimination between MFP and PDAC in patients with CP. Methods: Thirty CP patients with solid pancreatic lesions were prospectively enrolled: 15 with histologically confirmed PDAC and 15 with MFP. Traditional diagnostic parameters, including CA19-9 levels and EUS characteristics, were recorded but found insufficient for differentiation. EUS-FNA samples were analyzed using label-free mass spectrometry. A total of 928 proteins were identified in PDAC samples and 555 in MFP samples. Differential abundance analysis and pathway enrichment were performed. Results: Overall, 88 proteins showed significant differential abundance between PDAC and MFP samples, of which 26 met stringent statistical thresholds. Among these, Carboxylesterase 2 (CES2), Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1), Lumican (LUM), Transmembrane Protein 205 (TMEM205), and NAD(P)H Quinone Dehydrogenase 1 (NQO1) emerged as key discriminatory proteins. Pathway enrichment analysis revealed distinct biological processes between the groups, including mitochondrial fatty acid β-oxidation, Rho GTPase signaling, and platelet degranulation. Conclusions: Proteomic signatures derived from EUS-FNA samples offer a promising molecular approach to distinguish inflammatory pseudotumoral lesions from malignant pancreatic tumors in CP patients. This minimally invasive strategy could enhance diagnostic accuracy where current methods fall short. Further validation in larger, multicenter cohorts is warranted to confirm these findings and evaluate their clinical applicability.

Inflammatory bowel diseases(IBD), including mainly ulcerative colitis (UC) and Crohn's disease (CD), have been associated with cognitive and psychological changes, though the mechanisms remain unclear. This prospective case-control study aimed to evaluate cognitive performance, and biomarkers (homocysteine, serum amyloid A, brain derived neurotrophic factor and S100B protein) in IBD patients. A total of 90 individuals (34 UC, 21 CD, and 35 controls) were assessed using the Montreal Cognitive Assessment (MoCA), Memory Impairment Index (MIS), and biomarker analysis. MoCA and MIS testing showed significant differences between UC, CD and controls, with lower scores observed in IBD groups (p=0.003, p=0.015). Regarding trail making tests, digit symbol substitution test and forward and backward digit span, no significant changes were observed. No functional deficits were observed in daily activities. Biomarker analysis revealed lower brain-derived neurotrophic factor and higher serum amyloid A levels in IBD patients, correlated to MOCA and MIS score. There were no significant differences in psychological distress between IBD patients and controls. Subtle cognitive declines were noted across all groups during the 1-year follow-up, without any statistical significance when groups were compared. In conclusion, IBD patients reported lower cognitive scores compared to controls, while no differences in depression and anxiety scores were observed. Higher BDNF levels correlated with better cognitive functioning, while higher serum amyloid A correlated with lower cognitive functioning.

Maternal–fetal communication involves complex molecular exchanges that can be perturbed by chromosomal abnormalities. Despite the growing use of omics approaches in prenatal research, maternal urine remains underexplored as a non-invasive source of molecular information reflecting both systemic and pregnancy-specific processes. This study performed an exploratory, label-free mass spectrometry-based proteomic analysis of maternal urine from pregnancies with normal karyotype (n = 15) and those affected by fetal aneuploidy (n = 9; trisomy 21, 18, 13, or monosomy X). A total of 861 proteins were identified across all samples, of which 42 significantly differed between groups (p ≤ 0.05, |fold change| ≥ 1.2). Ten proteins, including TFF1, TFF3, KRT76, CD300, PVR, VWA1, FBLN1, FGA, AZGP1, and MAT1, were more abundant in aneuploid pregnancies, suggesting roles in immune modulation, epithelial restitution, metabolic control, and extracellular matrix remodeling. Conversely, 32 proteins with lower abundance were primarily involved in immune regulation, structural organization, and energy metabolism, consistent with impaired placental and vascular adaptation. These findings reveal distinct urinary proteomic signatures associated with fetal aneuploidy, highlighting biologically relevant pathways that may advance understanding of maternal–fetal metabolic communication.