Exosomal microRNA-342-5p secreted from adipose-derived mesenchymal stem cells mitigates acute kidney injury in sepsis mice by inhibiting TLR9

Abstract Background Sepsis-related acute kidney injury (AKI) is an inflammatory disease associated with extremely high mortality and health burden. This study explored the possibility of exosomes secreted by adipose-derived mesenchymal stem cells (AMSCs) serving as a carrier for microRNA (miR)-342-5p to alleviate sepsis-related AKI and investigated the possible mechanism. Methods Serum was obtained from 30 patients with sepsis-associated AKI and 30 healthy volunteers for the measurement of miR-342-5p, blood urea nitrogen (BUN), and serum creatinine (SCr) levels. For in vitro experiments, AMSCs were transfected with LV-miR-342-5p or LV-miR-67 to acquire miR-342-5p-modified AMSCs and miR-67-modified AMSCs, from which the exosomes (AMSC-Exo-342 and AMSC-Exo-67) were isolated. The human renal proximal tubular epithelial cell line HK-2 was induced by lipopolysaccharide (LPS) to construct a cellular model of sepsis. The expression of Toll-like receptor 9 (TLR9) was also detected in AKI cells and mouse models. The interaction between miR-342-5p and TLR9 was predicted by dual luciferase reporter gene assay. Results Detection on clinical serum samples showed that BUN, SCr, and TLR9 were elevated and miR-342-5p level was suppressed in the serum of patients with sepsis-associated AKI. Transfection with LV-miR-342-5p reinforced miR-342-5p expression in AMSCs and AMSC-secreted exosomes. miR-342-5p negatively targeted TLR9. LPS treatment enhanced TLR9 expression, reduced miR-342-5p levels, suppressed autophagy, and increased inflammation in HK-2 cells, while the opposite trends were observed in LPS-induced HK-2 cells exposed to AMSC-Exo-342, Rapa, miR-342-5p mimic, or si-TLR9. Additionally, the effects of AMSC-Exo-342 on autophagy and inflammation in LPS-induced cells could be weakened by 3-MA or pcDNA3.1-TLR9 treatment. Injection of AMSC-Exo-342 enhanced autophagy, mitigated kidney injury, suppressed inflammation, and reduced BUN and SCr levels in sepsis-related AKI mouse models. Conclusion miR-342-5p transferred by exosomes from miR-342-5p-modified AMSCs ameliorated AKI by inhibiting TLR9 to accelerate autophagy. Graphical Abstrac

Is Infant/Toddler Anemia a Problem across Rural China? A Mixed-Methods Analysis

In the past, iron-deficiency anemia in children has had a widespread presence in rural China. Given the recent economic growth in China, it is unclear if anemia among infants/toddlers remains a problem. The objective of this study is to measure the anemia rate in rural Chinese infants/toddlers across four major subpopulations and attempt to discover the sources of anemia. We use a mixed-methods approach combining quantitative data on 2909 rural Chinese infants/toddlers and their families with qualitative interviews with 84 caregivers of infants aged 6 to 30 months. Quantitative analysis indicates that the overall prevalence of anemia (43%) within sampled infants/toddlers was high, especially in comparison to the low rates of stunting (2–5%), being underweight (2%), and wasting (2–4%). These findings suggest that in rural China, anemia stems from the poor quality of the diets of infants/toddlers, rather than insufficient quantities of food being consumed. Qualitative analysis illustrates the factors that are contributing to anemia. Caregivers do not understand the causes of this condition, the symptoms that would lead one to recognize this condition, or the steps needed to treat their child with this condition. The findings offer a comprehensive understanding of the limited awareness of anemia among rural Chinese caregivers