Biology subjects

Matos, R.

Publications and source records attributed to Matos, R..

4 recordsLinked to original sources

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↗

bioRxiv2023

Helicobacter pylori attachment-blocking antibodies protect against duodenal ulcer disease

The majority of the world population carry the gastric pathogen Helicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism where H. pylori attachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority of H. pylori carriers. These antibodies block binding of the H. pylori attachment protein BabA by mimicking BabAs binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.

immunology↗

bioRxiv2021

Intestinal GCN2 controls Drosophila systemic growth upon AA imbalance in response to Lactiplantibacillus plantarum symbiotic cues encoded by r/tRNAoperons

Symbiotic bacteria interact with their host through symbiotic cues. Here, we took advantage of the mutualism between Drosophila and Lactiplantibacillus plantarum (Lp) to investigate a novel mechanism of host-symbiont interaction. Using chemically-defined diets, we found that association with Lp improves the growth of larvae fed amino acid-imbalanced diets, even though Lp cannot produce the limiting amino acid. We show that in this context Lp supports its hosts growth through a molecular dialog that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the GCN2 kinase in Drosophilas enterocytes. Our data indicate Lps r/tRNAs are packaged in extracellular vesicles and activate GCN2 in a subset of larval enterocytes, a mechanism necessary to remodel the intestinal transcriptome and ultimately to support anabolic growth. Based on our findings, we propose a novel beneficial molecular dialog between host and microbes, which relies on a non-canonical role of GCN2 as a mediator of non-nutritional symbiotic cues encoded by r/tRNA operons.

microbiology↗

bioRxiv2019

Do combinations of clinical parameters related to caries activity status predict progression more accurately than individual parameters?

Few studies have addressed the predictive power of the clinical parameters used in assessing caries lesion activity. This study assessed the predictive validity of evaluating clinical parameters that are related to caries lesion activity status, individually and combined, in a long-term analysis. The occlusal surfaces of primary molars (1361 surfaces) were examined in 205 children according to the following clinical features: potential for plaque stagnation, colour, luster, cavitation, texture, and clinical depth. Cavities with frankly exposed dentine were excluded from this sample. After 1 year, 148 children (828 surfaces) were re-evaluated using the International Caries Detection and Assessment System to assess caries lesion progression. Progression was set as an outcome to verify the predictive power of the initially assessed clinical parameters. Different combinations of two or more parameters were also tested to check for any association with caries progression. Multilevel Poisson regression analyses were performed and the relative risk for each parameter/combination tested was calculated by considering a confidence interval of 95%. Forty percent of the reassessed surfaces presented caries progression after 1 year. Despite their surface integrity, dentine caries lesions were approximately 10-fold more likely and enamel lesions were approximately three-fold more likely to progress than sound surfaces. Similarly, cavitated lesions showed the highest risk of progression compared to sound/non-cavitated lesions. When only non-cavitated surfaces were considered, roughness proved to be a risk factor for caries progression. In conclusion, the lesions presenting clinical involvement of the dentine and even those cavitations clinically involving only the enamel had a higher risk of progression compared to sound or non-cavitated surfaces. For these lesions, the evaluation of other conjoint parameters seems unnecessary. Nevertheless, surface roughness can be a useful feature in predicting the risk of non-cavitated caries lesion progression.

epidemiology↗