Biology subjects

Mariani, A.

Publications and source records attributed to Mariani, A..

3 recordsLinked to original sources

bioRxiv2024

Therapeutic potential of human mesenchymal stromal cell-derived mitochondria in a rat model of post-surgical digestive fistula: towards an energetic nano-biotherapy

BackgroundTissue regeneration heavily relies on cellular energy production, with mitochondria playing a crucial role. Dysfunctional mitochondria are implicated in various degenerative diseases, driving interest in targeting mitochondrial transplantation for tissue repair. Wound healing is highly compromised in gastrointestinal conditions resulting in fistula development, particularly after sleeve gastrectomy. Human mesenchymal stem/stromal cells (hMSCs) and their cell-free products such as mitochondria offer potential benefits due to their therapeutic properties on cellular energy production. Here we investigated the therapeutic advantage of hMSCs-derived mitochondria nano-biotherapy in a rat model of post-surgical fistula healing. MethodsViable and structurally intact mitochondria were isolated from hMSCs before exposure to human colonic epithelial cells (HCEC-1CT) culture or transplantation into a rat model of post-operative fistula. ResultsOur findings reveal significant dose-dependent improvement on cellular metabolic activity and ATP content of the recipient cells. Assessment of the external fistula orifice developed following post sleeve gastrectomy fistula, revealed a substantial healing in all transplanted rats compared to control group. ConclusionOur findings highlight the therapeutic potential of hMSCs-derived mitochondria in post-surgical fistula healing. This research contributes to advancing cell-free regenerative strategies for gastrointestinal conditions, offering new insights into mitochondrial-based therapies for enhancing wound healing and tissue repair.

systems biology↗

bioRxiv2024

Functional impact of the hyperduplication genomophenotype in high copy number endometrial cancer

High copy number endometrial cancers (HCNEC) are dominated by excessive duplications scattered across the genome, termed here as the HyperDuplication GenomoPhenotype (HDGP). Although correlated with cancer progression, its biological significance and implications for therapy have not yet been established. We identified locations and sizes of duplications in 171 endometrial cancer cases and designated 71 HCNEC cases as HDGP. We also investigated the response to the pan-ERBB inhibitor afatinib in a subset of HDGP-EC cases with ERBB2/ERBB3 duplications using a patient-derived three-dimensional culture model. Our analysis demonstrates that beyond tandem duplications there is a more general pattern involving coordinated duplication of multiple distant regions of the genome, demonstrating preferential selectivity to over-expressed potential oncogenes within a broad network. This suggests that HDGP increases tumor fitness and resistance to therapy by perturbing important gene networks in concert rather than only driver genes, suggesting a mechanistic basis for the ineffectiveness of targeted drugs in these patients and highlighting the need for combination therapies in these highly aggressive cases.

genomics↗

bioRxiv2024

Testing microbial biomining from asteroidal material onboard the International Space Station

Expanding human space exploration beyond Earths orbit necessitates efficient technologies for self-sustainable acquisition of local resources to overcome unviable resupply missions from Earth. Potential source of materials are asteroids, some of which contain valuable metals, such as platinum group elements. The BioAsteroid experiment, performed onboard the International Space Station, tested the use of microorganisms (bacteria and fungi) to carry out mining of useful elements from asteroidal material (L-chondrite) under microgravity, in support of a long-term human presence in space. The fungus Penicillium simplicissimum, enhanced the mean release of palladium, platinum and other elements from the meteorite material in microgravity, compared to non-biological leaching. However, there was large variability in the results. For many elements, non-biological leaching under microgravity was enhanced compared to terrestrial gravity, while bioleaching was unaffected. Metabolomics results revealed clear patterns that highlight the influence of space conditions on the microbial metabolism, particularly for P. simplicissimum. We identified the presence of carboxylic acids, and molecules of potential biomining and pharmaceutical interest, enhanced in microgravity. These results show a non-trivial effect of microgravity on bioleaching, highlighting the requirement of an optimal combination of microorganism(s), rock substrate, and conditions for successful biomining, both in space and Earth.

microbiology↗