Biology subjects

Carneiro, F.

Publications and source records attributed to Carneiro, F..

4 recordsLinked to original sources

bioRxiv2025

White Matter Microstructure Fingerprint of Cerebral Small Vessel Disease

BackgroundWhite matter hyperintensities (WMHs) are the imaging hallmark of cerebral small vessel disease (SVD), yet their microstructural composition, spatial heterogeneity, and relationship to diffuse normal-appearing white matter (NAWM) damage and cardiovascular risk remain incompletely defined. MethodsIn 363 community-dwelling adults from the BrainLaus cohort (mean age 55.5 years; range 19.8-89.4; 48.8% male), we combined quantitative relaxometry (MTsat, R1, R2*) and diffusion-derived metrics (FA, MD, NODDI, g-ratio). WMHs were automatically segmented on FLAIR and microstructure was quantified across lobes, white matter compartments, and geodesic layers extending from the WMH core into surrounding NAWM. Multivariate organisation was assessed using principal component analysis, and associations with cardiovascular risk factors were tested using partial least squares. ResultsOur analysis revealed demyelination, axonal loss, and extracellular fluid accumulation, particularly in periventricular regions. Layer-specific profiles showed a centrifugal gradient, with myelin loss and oedema at the core and axonal alteration in surrounding tissue. These signatures were associated with age-related cardiovascular risk factors, including higher blood pressure, bioimpedance, and lower hemoglobin levels. ConclusionWMHs index the endpoint of a broader, spatially structured white matter injury process that extends into NAWM, is regionally concentrated in periventricular tissue, and covaries with systemic vascular/metabolic factors. These findings support sustained vascular risk management to mitigate CSVD-related white matter degeneration.

neuroscience↗

bioRxiv2025

Patient-derived organoids to study glycosylation dynamics during gastric disease

BACKGROUND AND AIMSAberrant cellular glycosylation remains a key event that accompanies and actively sustains gastric neoplastic transformation. Patient-derived organoids (PDOs) have recently emerged as a promising ex vivo model to study human gastric disorders. Since the PDOs glycosylation landscape remains unknown, this study aims to evaluate PDOs as potential avatars of in vivo tissue glycosylation profiles in the gastric context. METHODSFresh gastric mucosa samples derived from non-tumoral obese patients (n=11), adjacent tumor mucosa samples (n=29), and tumor tissue samples derived from gastric cancer (GC) patients (n=30) were used to establish a biobank of gastric PDOs (n=56). The N- and O-glycophenotypes of normal, adjacent, and tumor PDOs and respective in vivo tissues were thoroughly characterized by immunostaining. Additionally, a comparative glycan analysis was performed over time, upon PDO biobanking and xenografting in mice. The binding of two Helicobacter pylori (H. pylori) isogenic strains with distinct glycan-binding affinities was assessed in parental gastric mucosa tissues and compared with the respective PDOs before and after modulation of their glycan landscape. RESULTSOur results show that PDOs mimic different phenotypes of the carcinogenic cascade and recapitulate parental gastric tissues glycosylation profile. Tumor PDOs recapitulate the inter- and intra-heterogeneity features observed in GC, which is maintained over time, upon biobanking and xenografting. We demonstrated that the expression of type I and type II Lewis antigens is dynamically controlled by PDOs differentiation status, which results in differential binding to H. pylori strains displaying distinct glycan-binding adhesins, mirroring the gastric epithelium tissue interactions. CONCLUSIONSThis study established PDOs as invaluable ex vivo tools to study the complex glycan dynamics in both gastric physiological and pathological settings.

cell biology↗

bioRxiv2020

Cis-regulatory similarities in the zebrafish and human pancreas uncover potential disease-related enhancers

Introductory paragraphThe pancreas is a central organ for human diseases that have a dramatic societal burden, such as pancreatic cancer and diabetes1,2. Non-coding cis-regulatory elements (CREs) of DNA control gene expression3,4, being required for proper pancreas function. Most disease-associated alleles5,6 are non-coding, often overlapping with CREs5, suggesting that alterations in these regulatory sequences contribute to human pancreatic diseases by impairing gene expression. However, functional testing of CREs in vivo is not fully explored. Here we analysed histone modifications, transcription, chromatin accessibility and interactions, to identify zebrafish pancreas CREs and their human functional equivalents, uncovering disease-associated sequences across species. We found a human pancreatic enhancer whose deletion impairs the tumour suppressor gene ARID1A expression, conferring a potential tumour suppressor role to this non-coding sequence. Additionally, we identified a zebrafish ptf1a distal enhancer which deletion generates pancreatic agenesis, demonstrating the causality of this condition in humans7 and the interspecies functional equivalency of enhancers.

genomics↗

bioRxiv2018

CD44v6 expression is a novel predictive marker of therapy response and poor prognosis in gastric cancer patients

Late diagnosis, modest treatment options and lack of predictive markers of therapy response dictate the poor overall survival (OS) of [~]1 year in most gastric cancer (GC) patients. We hypothesized that the level of CD44v6 expression in tumor cells could predict therapy response and prognosis in GC patients.\n\nWe analyzed a surgical tumor series of GC patients for the extension of CD44v6 membranous immuno-expression, clinical-pathological features, patient survival, and response to therapy. By integrating this information, we assessed the value of CD44v6 expression to predict benefit from current treatment regimens and prognosis in GC patients. We used GC cell lines and mouse xenografts to assess and/validate the biological impact of CD44v6 expression in GC cells behavior.\n\nWe demonstrated that GC patients whose tumors present higher levels of CD44v6 membranous expression benefit from adding chemotherapy to surgery as opposed to those without CD44v6 expression. Moreover, patients bearing CD44_high tumors presented worse OS than those bearing CD44_absent/low tumors, consolidating the role of CD44v6 expression as an independent factor of poor prognosis in this disease. Finally, our in vitro and patients data pinpoints the CD44v6+ cell population as the driver of tumor recurrence following conventional chemotherapy, in heterogeneous tumors composed by CD44v6- and CD44v6+ cells.\n\nOur study pioneers the identification of CD44v6 as a potential predictive marker of response to conventional chemotherapy, and consolidates CD44v6 as an independent marker of poor prognosis in GC. Overall, our data strongly supports selection of patients with high CD44v6 expressing tumors for conventional chemotherapy with or without surgery, regardless of the TNM stage.

cancer biology↗