AKI affects both quality of life and health care costs and is an independent risk factor for mortality. At present, there are few effective treatment options for AKI. Here, we describe a nonpharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia-reperfusion injury in mice, which is a model for human AKI. We exposed anesthetized mice to an ultrasound protocol 24 hours before renal ischemia. After 24 hours of reperfusion, ultrasound-treated mice exhibited preserved kidney morphology and function compared with sham-treated mice. Ultrasound exposure before renal ischemia reduced the accumulation of CD11b + Ly6G high neutrophils and CD11b + F4/80 high myeloid cells in kidney tissue. Furthermore, splenectomy and adoptive transfer studies revealed that the spleen and CD4 + T cells mediated the protective effects of ultrasound. Last, blockade or genetic deficiency of the a7 nicotinic acetylcholine receptor abrogated the protective effect of ultrasound, suggesting the involvement of the cholinergic anti-inflammatory pathway. Taken together, these results suggest that an ultrasound-based treatment could have therapeutic potential for the prevention of AKI, possibly by stimulating a splenic anti-inflammatory pathway.

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We showed previously that prior exposure to a modified ultrasound regimen prevents kidney ischemiareperfusion injury (IRI) likely via the splenic cholinergic anti-inflammatory pathway (CAP) and a7 nicotinic acetylcholine receptors (a7nAChR). However, it is unclear how ultrasound stimulates the splenic CAP. Further investigating the role of the spleen in ischemic injury, we found that prior splenectomy (-7d) or chemical sympathectomy of the spleen with 6-hydroxydopamine (6OHDA; -14d) exacerbated injury after subthreshold (24-minute ischemia) IRI. 6-OHDA-induced splenic denervation also prevented ultrasoundinduced protection of kidneys from moderate (26-minute ischemia) IRI. Ultrasound-induced protection required hematopoietic but not parenchymal a7nAChRs, as shown by experiments in bone marrow chimeras generated with wild-type and a7nAChR -/-mice. Ultrasound protection was associated with reduced expression of circulating and kidney-derived cytokines. However, splenocytes isolated from mice 24 hours after ultrasound treatment released more IL-6 ex vivo in response to LPS than splenocytes from sham mice. Adoptive transfer of splenocytes from ultrasound-treated (but not sham) mice to naïve mice was sufficient to protect kidneys of recipient mice from IRI. Ultrasound treatment 24 hours before cecal ligation puncture-induced sepsis was effective in reducing plasma creatinine in this model of AKI. Thus, splenocytes of ultrasound-treated mice are capable of modulating IRI in vivo, supporting our ongoing hypothesis that a modified ultrasound regimen has therapeutic potential for AKI and other inflammatory conditions.

Apple processing results in peel, stem, seeds, and pulp being left as a waste product known as apple pomace. This review comprehensively assessed apple pomace composition for nutritional value and bioactive substances and evaluated potential health benefits and safety. Apple pomace is a rich source of health-benefitting nutrients, including minerals, dietary fiber, antioxidants, and ursolic acid, which suggests it has potential use as a dietary supplement, functional food, and/or food additive. Preclinical studies have found apple pomace and its isolated extracts improved lipid metabolism, antioxidant status, and gastrointestinal function and had a positive effect on metabolic disorders (eg, hyperglycemia, insulin resistance, etc.). Safety studies have shown apple pomace to be a safe livestock feed additive and to have pesticide concentrations within safety thresholds established for human consumption. Commercial development of apple pomace for human consumption requires more research focusing on standardized methods of nutrient reporting, mechanistic studies, and human clinical trials.