Early and late gut microbiota signatures of stroke in high salt-fed stroke-prone spontaneously hypertensive rats.

The high salt-fed stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable tool to study the mechanisms underlying stroke pathogenesis. Salt intake modifies the gut microbiota (GM) in rats and humans and alterations of the GM have previously been associated with increased stroke occurrence. We aimed to characterize the GM profile in SHRSPs fed a high-salt stroke-permissive diet (Japanese diet, JD), compared to the closely related stroke-resistant control (SHRSR), to identify possible changes associated with stroke occurrence. SHRSPs and SHRSRs were fed a regular diet or JD for 4 weeks (short-term, ST) or a maximum of 10 weeks (long-term, LT). Stroke occurred in SHRSPs on JD-LT, preceded by proteinuria and diarrhoea. The GM of JD-fed SHRSPs underwent early and late compositional changes compared to SHRSRs. An overrepresentation of Streptococcaceae and an underrepresentation of Lachnospiraceae were observed in SHRSPs JD-ST, while in SHRSPs JD-LT short-chain fatty acid producers, e.g. Lachnobacterium and Faecalibacterium, decreased and pathobionts such as Coriobacteriaceae and Desulfovibrio increased. Occludin gene expression behaved differently in SHRSPs and SHRSRs. Calprotectin levels were unchanged. In conclusion, the altered GM in JD-fed SHRSPs may be detrimental to gut homeostasis and contribute to stroke occurrence.

Efficacy of Stem Cell Therapy in Large Animal Models of Ischemic Cardiomyopathies: A Systematic Review and Meta-Analysis.

Stem-cell therapy provides a promising strategy for patients with ischemic heart disease. In recent years, numerous studies related to this therapeutic approach were performed; however, the results were often heterogeneous and contradictory. For this reason, we conducted a systematic review and meta-analysis of trials, reporting the use of stem-cell treatment against acute or chronic ischemic cardiomyopathies in large animal models with regard to Left Ventricular Ejection Fraction (LVEF). The defined research strategy was applied to the PubMed database to identify relevant studies published from January 2011 to July 2021. A random-effect meta-analysis was performed on LVEF mean data at follow-up between control and stem-cell-treated animals. In order to improve the definition of the effect measure and to analyze the factors that could influence the outcomes, a subgroup comparison was conducted. Sixty-six studies (n = 1183 animals) satisfied our inclusion criteria. Ischemia/reperfusion infarction was performed in 37 studies, and chronic occlusion in 29 studies; moreover, 58 studies were on a pig animal model. The meta-analysis showed that cell therapy increased LVEF by 7.41% (95% Confidence Interval 6.23−8.59%; p < 0.001) at follow-up, with significative heterogeneity and high inconsistency (I2 = 82%, p < 0.001). By subgroup comparison, the follow-up after 31−60 days (p = 0.025), the late cell injection (>7 days, p = 0.005) and the route of cellular delivery by surgical treatment (p < 0.001) were significant predictors of LVEF improvement. This meta-analysis showed that stem-cell therapy may improve heart function in large animal models and that the swine specie is confirmed as a relevant animal model in the cardiovascular field. Due to the significative heterogeneity and high inconsistency, future translational studies should be designed to take into account the evidenced predictors to allow for the reduction of the number of animals used.