Biology subjects

Santin, Y.

Publications and source records attributed to Santin, Y..

3 recordsLinked to original sources

bioRxiv2025

Robust non-invasive detection of hyperglycemia in mouse models of metabolic dysregulation: the novel Urination Index biomarker

Blood glucose is one of the most essential parameters in metabolic research. Yet, accurate blood glucose monitoring in mouse models of diabetes is challenging due to the significant stress associated with the measurements and the variability in diabetes development among experimental mouse models. This variability necessitates frequent blood glucose measurements, which only provide intermittent data and may not accurately reflect continuous metabolic changes. To address these issues, we have utilized the Tecniplast DVC system to monitor bedding moisture, enabling the detection of increased urination (polyuria), a primary symptom of diabetes. Polyuria is a hallmark of (undiagnosed/untreated) diabetes, and we revealed high correlations between bedding moisture and blood glucose during hyperglycemia. Thus, our developed algorithm enhances animal welfare by reducing the need for invasive blood glucose tests and enabling non-invasive, continuous assessment of hyperglycemia onset, progression, and severity directly within the mices home cage. Continuous monitoring of polyuria allows detailed analysis of temporal and circadian urination patterns and enables assessment of the efficacy of glucose-lowering interventions, which is crucial in developing new pharmacological treatments. We propose that this innovative approach of a novel digital biomarker, the Urination Index (UI), offers a significant advance in the methodology for diabetes research in mouse models, improves animal welfare by reducing the need for invasive blood glucose tests, and enhances the reliability of data and the quality of life for the animals involved.

physiology↗

bioRxiv2024

Pathogenicity of Commensal Gut Biofilm In Prefrail Aging

Pathophysiological mechanisms of unhealthy aging, particularly the transition from robustness to frailty, remain poorly understood. Despite extensive microbiome research on taxonomy, the behavior of early prefrail gut bacteria in their natural community-host mucosal tissue context remains unexplored. Using fecal samples from the INSPIRE-T aging human cohort, we characterized gut microbiota phenotype during prefrailty stages using a polymicrobial biofilm model. Results revealed that prefrail-derived biofilms exhibited distinct taxonomic and physical alterations, enhanced dispersal, and increased epithelial virulence compared to robust counterparts. Multiparametric analyses linked biofilm characteristics to clinical traits, suggesting their potential as aging status indicators. Polyphenol-rich grape pomace extract partially reversed prefrail biofilm alterations and reduced proinflammatory prefrail biofilm responses in vitro. Microbiota from prefrail aged mice induced colon damage in antibiotic-treated recipients, establishing a prefrail microbiome-inflammation causality. Overall, the findings identified novel prefrail microbiome characteristics, established causal inflammatory links, and support microbiota-targeted geroprotective interventions for the prefrail populations.

microbiology↗

bioRxiv2020

Clearance of senescent cells during cardiac ischemia-reperfusion injury improves heart recovery following myocardial infarction

A key component of cardiac ischemia-reperfusion injury (IRI) is the increased generation of reactive oxygen species, leading to enhanced inflammation and tissue dysfunction in patients following intervention for myocardial infarction. In this study we hypothesized that oxidative stress, due to ischemia-reperfusion, induces senescence which contributes to the pathophysiology of cardiac IRI. We demonstrate that IRI induces cellular senescence in both cardiomyocytes and interstitial cell populations and treatment with the senolytic drug navitoclax after ischemia-reperfusion improves left ventricular function, increases myocardial vascularization, and decreases scar size. SWATH-MS based proteomics reveal that biological processes associated with fibrosis and inflammation, that were increased following ischemia-reperfusion, were attenuated upon senescent cell clearance. Furthermore, navitoclax treatment reduced the expression of proinflammatory, profibrotic and anti-angiogenic cytokines, including interferon gamma-induced protein-10, TGF-{beta}3, interleukin-11, interleukin-16 and fractalkine. Our study provides proof-of-concept evidence that cellular senescence contributes to impaired heart function and adverse remodeling following cardiac ischemia-reperfusion. We also establish that post-IRI senescent cells play a considerable role in the inflammatory response. Subsequently, senolytic treatment, at a clinically feasible time point, attenuates multiple components of this response and improves clinically important parameters. Thus, cellular senescence represents a potential novel therapeutic avenue to improve patient outcomes following cardiac ischemia-reperfusion.

cell biology↗