Tanshinone IIA-loaded nanoparticles and neural stem cell combination therapy improves gut homeostasis and recovery in a pig ischemic stroke model.

Autor: Jeon JH; Department of Nutritional Sciences, University of Georgia, Athens, GA, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA., Kaiser EE; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA., Waters ES; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA.; Environmental Health Science Department, University of Georgia, Athens, GA, USA., Yang X; Department of Chemistry, University of Georgia, Athens, GA, USA., Lourenco JM; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA., Fagan MM; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA., Scheulin KM; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA., Sneed SE; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA., Shin SK; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, USA., Kinder HA; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA., Kumar A; Department of Chemistry, University of Georgia, Athens, GA, USA., Platt SR; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, USA., Ahn J; Department of Statistics, University of Georgia, Athens, GA, USA.; Department of Industrial and Systems Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea., Duberstein KJ; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA., Rothrock MJ Jr; US National Poultry Research Center, USDA-ARS, Athens, GA, USA., Callaway TR; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA., Xie J; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Department of Chemistry, University of Georgia, Athens, GA, USA., West FD; Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, USA.; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA, USA., Park HJ; Department of Nutritional Sciences, University of Georgia, Athens, GA, USA. hjpark@uga.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Feb 13; Vol. 13 (1), pp. 2520. Date of Electronic Publication: 2023 Feb 13.
DOI: 10.1038/s41598-023-29282-9
Abstrakt: Impaired gut homeostasis is associated with stroke often presenting with leaky gut syndrome and increased gut, brain, and systemic inflammation that further exacerbates brain damage. We previously reported that intracisternal administration of Tanshinone IIA-loaded nanoparticles (Tan IIA-NPs) and transplantation of induced pluripotent stem cell-derived neural stem cells (iNSCs) led to enhanced neuroprotective and regenerative activity and improved recovery in a pig stroke model. We hypothesized that Tan IIA-NP + iNSC combination therapy-mediated stroke recovery may also have an impact on gut inflammation and integrity in the stroke pigs. Ischemic stroke was induced, and male Yucatan pigs received PBS + PBS (Control, n = 6) or Tan IIA-NP + iNSC (Treatment, n = 6) treatment. The Tan IIA-NP + iNSC treatment reduced expression of jejunal TNF-α, TNF-α receptor1, and phosphorylated IkBα while increasing the expression of jejunal occludin, claudin1, and ZO-1 at 12 weeks post-treatment (PT). Treated pigs had higher fecal short-chain fatty acid (SCFAs) levels than their counterparts throughout the study period, and fecal SCFAs levels were negatively correlated with jejunal inflammation. Interestingly, fecal SCFAs levels were also negatively correlated with brain lesion volume and midline shift at 12 weeks PT. Collectively, the anti-inflammatory and neuroregenerative treatment resulted in increased SCFAs levels, tight junction protein expression, and decreased inflammation in the gut.
(© 2023. The Author(s).)
Databáze: MEDLINE
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