Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut−liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.
Data regarding the association between subclinical thyroid dysfunction and clinical outcomes in ischemic stroke patients with intravenous thrombolysis (IVT) are limited. We aimed to investigate the predictive value of subclinical thyroid dysfunction in END, functional outcome and mortality at 3 months among IVT patients. We prospectively recruited 563 IVT patients from 5 stroke centers in China. Thyroid function status was classified as subclinical hypothyroidism, subclinical hyperthyroidism (SHyper) and euthyroidism. The primary outcome was END, defined as ≥ 4 point in the NIHSS score within 24 h after IVT. Secondary outcomes included 3-month functional outcome and mortality. Of the 563 participants, END occurred in 14.7%, poor outcome in 50.8%, and mortality in 9.4%. SHyper was an independent predictor of END [odd ratio (OR), 4.35; 95% confidence interval [CI], 1.86–9.68, P = 0.003], 3-month poor outcome (OR, 3.24; 95% CI, 1.43–7.33, P = 0.005) and mortality [hazard ratio, 2.78; 95% CI, 1.55–5.36, P = 0.003]. Subgroup analysis showed that there was no significant relationship between SHyper and clinical outcomes in IVT patients with endovascular therapy. In summary, SHyper is associated with increased risk of END, and poor outcome and mortality at 3 months in IVT patients without endovascular therapy.
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