by Keyword: colon
Cañellas-Socias A, Cortina C, Hernando-Momblona X, Palomo-Ponce S, Mulholland EJ, Turon G, Mateo L, Conti S, Roman O, Sevillano M, Slebe F, Stork D, Caballé-Mestres A, Berenguer-Llergo A, Álvarez-Varela A, Fenderico N, Novellasdemunt L, Jiménez-Gracia L, Sipka T, Bardia L, Lorden P, Colombelli J, Heyn H, Trepat X, Tejpar S, Sancho E, Tauriello DVF, Leedham S, Attolini CS, Batlle E, (2022). Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells Nature 611, 603-613
Around 30-40% of patients with colorectal cancer (CRC) undergoing curative resection of the primary tumour will develop metastases in the subsequent years1. Therapies to prevent disease relapse remain an unmet medical need. Here we uncover the identity and features of the residual tumour cells responsible for CRC relapse. An analysis of single-cell transcriptomes of samples from patients with CRC revealed that the majority of genes associated with a poor prognosis are expressed by a unique tumour cell population that we named high-relapse cells (HRCs). We established a human-like mouse model of microsatellite-stable CRC that undergoes metastatic relapse after surgical resection of the primary tumour. Residual HRCs occult in mouse livers after primary CRC surgery gave rise to multiple cell types over time, including LGR5+ stem-like tumour cells2-4, and caused overt metastatic disease. Using Emp1 (encoding epithelial membrane protein 1) as a marker gene for HRCs, we tracked and selectively eliminated this cell population. Genetic ablation of EMP1high cells prevented metastatic recurrence and mice remained disease-free after surgery. We also found that HRC-rich micrometastases were infiltrated with T cells, yet became progressively immune-excluded during outgrowth. Treatment with neoadjuvant immunotherapy eliminated residual metastatic cells and prevented mice from relapsing after surgery. Together, our findings reveal the cell-state dynamics of residual disease in CRC and anticipate that therapies targeting HRCs may help to avoid metastatic relapse.© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
JTD Keywords: colonization, defines, human colon, mutations, plasticity, retrieval, stem-cells, subtypes, underlie, Comprehensive molecular characterization
Altay G, Abad-Lázaro A, Gualda EJ, Folch J, Insa C, Tosi S, Hernando-Momblona X, Batlle E, Loza-Álvarez P, Fernández-Majada V, Martinez E, (2022). Modeling Biochemical Gradients In Vitro to Control Cell Compartmentalization in a Microengineered 3D Model of the Intestinal Epithelium Advanced Healthcare Materials 11, 2201172
Gradients of signaling pathways within the intestinal stem cell (ISC) niche are instrumental for cellular compartmentalization and tissue function, yet how are they sensed by the epithelium is still not fully understood. Here a new in vitro model of the small intestine based on primary epithelial cells (i), apically accessible (ii), with native tissue mechanical properties and controlled mesh size (iii), 3D villus-like architecture (iv), and precisely controlled biomolecular gradients of the ISC niche (v) is presented. Biochemical gradients are formed through hydrogel-based scaffolds by free diffusion from a source to a sink chamber. To confirm the establishment of spatiotemporally controlled gradients, light-sheet fluorescence microscopy and in-silico modeling are employed. The ISC niche biochemical gradients coming from the stroma and applied along the villus axis lead to the in vivo-like compartmentalization of the proliferative and differentiated cells, while changing the composition and concentration of the biochemical factors affects the cellular organization along the villus axis. This novel 3D in vitro intestinal model derived from organoids recapitulates both the villus-like architecture and the gradients of ISC biochemical factors, thus opening the possibility to study in vitro the nature of such gradients and the resulting cellular response.© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
JTD Keywords: biomolecular gradients, colon, crypt, engineering organoids, hydrogels, identification, in silico modeling, intestinal stem cell niches, light sheet fluorescence microscopy, niche, permeability, photolithography, regeneration, villus, wnt, 3d architectures, Biomolecular gradients, Engineering organoids, In silico modeling, Intestinal stem cell niches, Light sheet fluorescence microscopy, Photolithography, Stem-cell
Oliveira LFD, Mallafré-Muro C, Giner J, Perea L, Sibila O, Pardo A, Marco S, (2022). Breath analysis using electronic nose and gas chromatography-mass spectrometry: A pilot study on bronchial infections in bronchiectasis Clinica Chimica Acta 526, 6-13
Background and aims: In this work, breath samples from clinically stable bronchiectasis patients with and without bronchial infections by Pseudomonas Aeruginosa- PA) were collected and chemically analysed to determine if they have clinical value in the monitoring of these patients. Materials and methods: A cohort was recruited inviting bronchiectasis patients (25) and controls (9). Among the former group, 12 members were suffering PA infection. Breath samples were collected in Tedlar bags and analyzed by e-nose and Gas Chromatography-Mass Spectrometry (GC-MS). The obtained data were analyzed by chemometric methods to determine their discriminant power in regards to their health condition. Results were evaluated with blind samples. Results: Breath analysis by electronic nose successfully separated the three groups with an overall classification rate of 84% for the three-class classification problem. The best discrimination was obtained between control and bronchiectasis with PA infection samples 100% (CI95%: 84–100%) on external validation and the results were confirmed by permutation tests. The discrimination analysis by GC-MS provided good results but did not reach proper statistical significance after a permutation test. Conclusions: Breath sample analysis by electronic nose followed by proper predictive models successfully differentiated between control, Bronchiectasis and Bronchiectasis PA samples. © 2021 The Author(s)
JTD Keywords: biomarkers, breath analysis, bronchiectasis, diagnosis, e-nose, fingerprints, gc-ms, identification, lung-cancer, partial least-squares, pseudomonas-aeruginosa, signal processing, validation, volatile organic-compounds, Airway bacterial-colonization, Breath analysis, Bronchiectasis, E-nose, Gc-ms, Signal processing
Freire R, Mego M, Oliveira LF, Mas S, Azpiroz F, Marco S, Pardo A, (2022). Quantitative GC–TCD Measurements of Major Flatus Components: A Preliminary Analysis of the Diet Effect Sensors 22, 838
The impact of diet and digestive disorders in flatus composition remains largely unexplored. This is partially due to the lack of standardized sampling collection methods, and the easy atmospheric contamination. This paper describes a method to quantitatively determine the major gases in flatus and their application in a nutritional intervention. We describe how to direct sample flatus into Tedlar bags, and simultaneous analysis by gas chromatography–thermal conductivity detection (GC–TCD). Results are analyzed by univariate hypothesis testing and by multilevel principal component analysis. The reported methodology allows simultaneous determination of the five major gases with root mean measurement errors of 0.8% for oxygen (O2), 0.9% for nitrogen (N2), 0.14% for carbon dioxide (CO2), 0.11% for methane (CH4), and 0.26% for hydrogen (H2). The atmospheric contamination was limited to 0.86 (95% CI: [0.7–1.0])% for oxygen and 3.4 (95% CI: [1.4–5.3])% for nitrogen. As an illustration, the method has been successfully applied to measure the response to a nutritional intervention in a reduced crossover study in healthy subjects. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
JTD Keywords: breath, colonic microbiota, diet effect on flatus, disorders, evacuation, excretion, flatulence, hydrogen gas, major flatus gas components, multilevel principal component analysis, rectal gas collection, systems, volume, Atmospheric contamination, Carbon dioxide, Conductivity detection, Diet effect on flatus, Gas chromatography, Gas collections, Gas component, Gases, Major flatus gas component, Major flatus gas components, Multilevel principal component analyse, Multilevel principal component analysis, Multilevels, Nitrogen, Nutrition, Oxygen, Principal component analysis, Principal-component analysis, Rectal gas collection, Volatile organic-compounds
Hodásová L, Sans J, Molina BG, Alemán C, Llanes L, Fargas G, Armelin E, (2021). Polymer infiltrated ceramic networks with biocompatible adhesive and 3D-printed highly porous scaffolds Additive Manufacturing 39, 101850
© 2021 Elsevier B.V. Herein, for the first time is described the design of a novel porous zirconia scaffolds manufactured by using polymer-infiltrated ceramic network (PICN) and 3D-printing technologies. Cubic geometry of pieces was obtained by perpendicular layer-by-layer deposition of yttrium-stabilized tetragonal zirconia polycrystal (3Y-TZP) and Pluronic® hydrogel ceramic paste. The specimens were prepared by robocasting assembly with 50% infill and 50% of pores, as feed setup. Bisphenol A glycerolate dimethacrylate (Bis-GMA) and tri(ethylenglycol) dimethacrylate (TEGDMA) copolymer, a well-known biocompatible adhesive, which is widely used in dentistry field, was employed to reinforce the pores of the 3D-printed ceramic structure. The success of the acrylate polymer infiltration above the scaffold surface and among the 3Y-TZP filaments was achieved through previous ceramic functionalization with 3-(trimethoxysilyl)propyl methacrylate (γ-MPS). The well infiltration of the material on pores was evaluated by gravimetry, obtaining a value of 87.5 ± 6.6% of pores covered by the adhesive. Such successful infiltration of methacrylate copolymer had also a positive effect on the mechanical properties of the scaffold material, being the PICN sample that one with the highest elongation resistance. The new system showed reduced bacteria proliferation, over 24 h of incubation with Gram-negative Escherichia coli and Gram-positive Streptococcus salivarius bacteria lines, when compared to the control.
JTD Keywords: acrylate polymer, bacteria colonization, yttrium stabilized zirconia, Acrylate polymer, Bacteria colonization, Robocasting, Yttrium stabilized zirconia
Castangia, I., Nácher, A., Caddeo, C., Merino, V., Díez-Sales, O., Catalán-Latorre, A., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2015). Therapeutic efficacy of quercetin enzyme-responsive nanovesicles for the treatment of experimental colitis in rats Acta Biomaterialia 13, 216-227
Biocompatible quercetin nanovesicles were developed by coating polyethylene glycol-containing vesicles with chitosan and nutriose, aimed at targeting the colon. Uncoated and coated vesicles were prepared using hydrogenated soy phosphatidylcholine and quercetin, a potent natural anti-inflammatory and antioxidant drug. Physicochemical characterization was carried out by light scattering, cryogenic microscopy and X-ray scattering, the results showing that vesicles were predominantly multilamellar and around 130 nm in size. The in vitro release of quercetin was investigated under different pH conditions simulating the environment of the gastrointestinal tract, and confirmed that the chitosan/nutriose coating improved the gastric resistance of vesicles, making them a potential carrier system for colon delivery. The preferential localization of fluorescent vesicles in the intestine was demonstrated using the In Vivo FX PRO Imaging System. Above all, a marked amelioration of symptoms of 2,4,6-trinitrobenzenesulfonic acid-induced colitis was observed in animals treated with quercetin-loaded coated vesicles, favoring the restoration of physiological conditions. Therefore, quercetin-loaded chitosan/nutriose-coated vesicles can represent a valuable therapeutic tool for the treatment of chronic intestinal inflammatory diseases, and presumably a preventive system, due to the synergic action of antioxidant quercetin and beneficial prebiotic effects of the chitosan/nutriose complex.
JTD Keywords: Chitosan/nutriose complex, Colon targeting, Phospholipid vesicles, Quercetin, Rat colitis