Human Intestinal Organoids and Microphysiological Systems for Modeling Radiotoxicity and Assessing Radioprotective Agents

Radiotherapy is a commonly employed treatment for colorectal cancer, yet its radiotoxicity-related impact on healthy tissues raises significant health concerns. This highlights the need to use radioprotective agents to mitigate these side effects. This review presents the current landscape of human translational radiobiology, outlining the limitations of existing models and proposing engineering solutions. We delve into radiotherapy principles, encompassing mechanisms of radiation-induced cell death and its influence on normal and cancerous colorectal cells. Furthermore, we explore the engineering aspects of microphysiological systems to represent radiotherapy-induced gastrointestinal toxicity and how to include the gut microbiota to study its role in treatment failure and success. This review ultimately highlights the main challenges and future pathways in translational research for pelvic radiotherapy-induced toxicity. This is achieved by developing a humanized in vitro model that mimics radiotherapy treatment conditions. An in vitro model should provide in-depth analyses of host-gut microbiota interactions and a deeper understanding of the underlying biological mechanisms of radioprotective food supplements. Additionally, it would be of great value if these models could produce high-throughput data using patient-derived samples to address the lack of human representability to complete clinical trials and improve patients’ quality of life

Moria del kiwi: alterazione della struttura anatomica e morfologica delle radici di actinidia sottoposte a condizioni di asfissia del suolo

produzione negli ultimi anni a causa della diffusione della sindrome del declino dell’actinidia (KVDS/moria). Sintomi simili al KVDS sono stati osservati in diversi ambienti e vengono spesso associati a ristagno idrico e asfissia radicale, con conseguente marciume radicale. Nell'ambito del progetto Zespri “Water and soil management of G3 in Italy”, nel 2020 è stata avviata la sperimentazione in actinidieti colpiti da moria a Latina (Lazio, - ET0 732 mm) al fine di indagare sulle possibili cause e suggerire delle soluzioni per contrastare questa fisiopatia. Sono stati raccolti campioni di radici da piante sane e confrontati con campioni raccolti da piante affette da KVDS. Per l’analisi microscopica, le radici sono state fissate in formalina al 10%, disidratate e incluse in paraffina. Ogni singolo campione è stato sezionato in sezioni dello spessore di 5 μm e colorate con diverse metodiche. Macroscopicamente, le radici affette da KVDS sono risultate marcescenti, mostrando una perdita di rizoderma e parenchima corticale. L’analisi microscopica ha rilevato danneggiamenti del sistema radicale con rottura e decomposizione tissutale, sfaldamento di rizoderma, area corticale con evidente perdita di turgore cellulare, disfacimento iniziale della stele ed evidente distacco della corteccia dai tessuti conduttori centrali. Nel campione di controllo, le radici hanno presentato un rizoderma con spessore di 13 μm e una dimensione media di cellule del parenchima di 44,5 μm, a differenza del campione KVDS, in cui lo spessore del rizoderma, quasi assente, è stato di 8,3 μm e la dimensione media delle cellule di 34,7 μm. Dall’analisi dei gas tellurici è emerso che, conseguentemente all'insorgenza del ristagno idrico nel suolo, nei suoli attorno alle piante colpite da KVDS, il potenziale redox, parametro inversamente correlato alla concentrazione di ossigeno, è risultato essere significativamente più basso (+331 vs. +368 mV; media 0-90 cm di profondità), mentre sono state riscontrate concentrazioni più elevate di CO2 (7467 vs. 5870 ppm; media 0-90 cm di profondità), un indicatore di condizioni anossiche del suolo. Per migliorare le qualità fisica del suolo e assicurare una crescita ottimale delle radici di actinidia, sarà applicata una gestione innovativa del suolo volta ad aumentarne la sostanza organica e ridurre la compattazione, facilitando il movimento orizzontale e verticale dell'acqua nel terreno per fornire alle radici di actinidia l'ossigeno necessario per mitigare gli effetti di microrganismi potenzialmente patogeni, molti dei quali proliferano in ambienti anaerobi. Sarà, infine, ottimizzata la gestione della chioma e dell’apparato radicale per bilanciare il rapporto tra radici e foglie e migliorare la capacità delle piante di riprendersi da questo declino fisiologico

Enhancing European capabilities for application of multi-omics studies in biology and biomedicine space research

Following on from the NASA twins’ study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA's GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research

ERα-LBD, an isoform of estrogen receptor alpha, promotes breast cancer proliferation and endocrine resistance

Estrogen receptor alpha (ER alpha) drives mammary gland development and breast cancer (BC) growth through an evolutionarily conserved linkage of DNA binding and hormone activation functions. Therapeutic targeting of the hormone binding pocket is a widely utilized and successful strategy for breast cancer prevention and treatment. However, resistance to this endocrine therapy is frequently encountered and may occur through bypass or reactivation of ER-regulated transcriptional programs. We now identify the induction of an ER alpha isoform, ER alpha-LBD, that is encoded by an alternative ESR1 transcript and lacks the activation function and DNA binding domains. Despite lacking the transcriptional activity, ER alpha-LBD is found to promote breast cancer growth and resistance to the ER alpha antagonist fulvestrant. ER alpha-LBD is predominantly localized to the cytoplasm and mitochondria of BC cells and leads to enhanced glycolysis, respiration and stem-like features. Intriguingly, ER alpha-LBD expression and function does not appear to be restricted to cancers that express full length ER alpha but also promotes growth of triple-negative breast cancers and ER alpha-LBD transcript (ESR1-LBD) is also present in BC samples from both ER alpha(+) and ER alpha(-) human tumors. These findings point to ER alpha-LBD as a potential mediator of breast cancer progression and therapy resistance

Proteome-wide analysis and diel proteomic profiling in the cyanobacterium Arthrospira platensis PCC 8005

The filamentous cyanobacteriumArthrospira platensishas a long history of use as a food supply and it has been used by the European Space Agency in the MELiSSA project, an artificial microecosystem which supports life during long-term manned space missions. This study assesses progress in the field of cyanobacterial shotgun proteomics and light/dark diurnal cycles by focusing onArthrospira platensis. Several fractionation workflows including gel-free and gel-based protein/peptide fractionation procedures were used and combined with LC-MS/MS analysis, enabling the overall identification of 1306 proteins, which represents 21% coverage of the theoretical proteome. A total of 30 proteins were found to be significantly differentially regulated under light/dark growth transition. Interestingly, most of the proteins showing differential abundance were related to photosynthesis, the Calvin cycle and translation processes. A novel aspect and major achievement of this work is the successful improvement of the cyanobacterial proteome coverage using a 3D LC-MS/MS approach, based on an immobilized metal affinity chromatography, a suitable tool that enabled us to eliminate the most abundant protein, the allophycocyanin. We also demonstrated that cell growth follows a light/dark cycle inA. platensis. This preliminary proteomic study has highlighted new characteristics of theArthrospira platensisproteome in terms of diurnal regulation

Space omics research in Europe: contributions, geographical distribution and ESA member state funding schemes

18 p.-3 fig.-1 graph. abst.The European research community, via European Space Agency (ESA) spaceflight opportunities, has significantly contributed towards our current understanding of spaceflight biology. Recent molecular biology experiments include “omic” analysis, which provides a holistic and systems level understanding of the mechanisms underlying phenotypic adaptation. Despite vast interest in, and the immense quantity of biological information gained from space omics research, the knowledge of ESA-related space omics works as a collective remains poorly defined due to the recent exponential application of omics approaches in space and the limited search capabilities of pre-existing records. Thus, a review of such contributions is necessary to clarify and promote the development of space omics among ESA and ESA state members. To address this gap, in this review we: i) identified and summarised omics works led by European researchers, ii) geographically described these omics works, and iii) highlighted potential caveats in complex funding scenarios among ESA member states.All listed authors are members of the ESA Space Omics Topical Team, funded by the ESA grant/contract 4000131202/20/NL/PG/pt “Space Omics: Towards an integrated ESA/NASA –omics database for spaceflight and ground facilities experiments” awarded to RH, which was the main funding source for this work. Individual authors also acknowledge support from: the Medical Research Council part of a Skills Development Fellowship [grant number MR/T026014/1] awarded to CSD; the Spanish CAM TALENTO program project 2020-5A_BIO-19724 to MAFR; the Spanish Plan Estatal de Investigación Científica y Desarrollo Tecnológico Grant RTI2018-099309-B-I00 to FJM, the Swedish Research Council VR grant 2020-04864 to SG and the French Centre National d'Etudes Spatiales grant DAR 2020-4800001004, 2021-4800001117 to ECD. This research was also funded in part by the Wellcome Trust [110182/Z/15/Z] to KS.Peer reviewe

Enhancing European capabilities for application of multi-omics studies in biology and biomedicine space research

Following on from the NASA twins’ study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA’s GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research