The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and IL-4, and decreased Treg cells and IFN-γ. In patients experiencing asthma, mTOR activation was positively correlated with the loss of Th17/Treg and Th1/Th2 balance. The role of mTOR in asthma was further confirmed using an ovalbumin-induced asthmatic mouse model. The mTOR pathway was activated in asthmatic mice, demonstrated by elevated levels of p-PI3K, p-Akt, p-mTOR, and p-p70S6k, and this activation was significantly reduced by treatment with budenoside or mTOR pathway inhibitors. Moreover, mTOR pathway inhibitor treatment reduced asthmatic markers and reversed the Th17/Treg and Th1/Th2 imbalances in asthmatic mice. Finally, different mTOR pathway inhibitor treatments have different inhibitory effects on signaling molecules in asthmatic mice. In summary, mTOR is activated during asthma onset and suppressed during asthma remission, and inhibiting the mTOR pathway in asthmatic mice alleviates asthmatic markers and restores the balances of Th17/Treg and Th1/Th2 cytokines. These data strongly suggest a critical requirement for mTOR pathway activation in asthma onset, suggesting potential targets for asthma treatments.

ObjectiveTo investigate myeloid-derived suppressor cell (MDSC) accumulation and interleukin 10 (IL-10) and interleukin 12 (IL-12) levels during the onset of asthma in both pediatric patients and mouse models, as well as their possible roles in the development of asthma.MethodsPeripheral blood samples were gathered from children with asthma attacks (attack group) and alleviated asthma (alleviated group), as well as two control groups, children with pneumonia and healthy children. The pathological characteristics of asthma in asthmatic mice, budesonide-treated asthmatic mice, and normal control mice were also evaluated by immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining.ResultsMDSC accumulation and serum IL-10 levels were significantly elevated in the children with asthma compared with the budesonide-treated alleviated group, normal healthy controls, and pneumonia controls (p<0.05), whereas those in the latter three groups showed no statistical differences (p>0.05). The level of serum IL-12 in the asthmatic children was drastically reduced compared to the budesonide-treated alleviated group, healthy controls, and pneumonia controls (p<0.05), whereas the latter three groups showed no significant differences in their serum IL-12 levels. The percentage of MDSCs in children with asthma was positively correlated with the level of serum IL-10 and negatively correlated with the level of serum IL-12. The levels of MDSCs and IL-10 in asthmatic mice were significantly higher than those in the normal control mice (both p<0.05) and were reduced after budesonide treatment (both p<0.05). IL-12 expression in the asthmatic mice was significantly lower than the control and was increased upon budesonide treatment (both p<0.05).ConclusionDuring the onset of asthma, the accumulation of MDSCs and the level of serum IL-10 increase, while the level of IL-12 decreases. These fluctuations may play an important role in the development of asthma.

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Objective Exosomes, membranous nanovesicles, naturally bringing proteins, mRNAs, and microRNAs (miRNAs), play crucial roles in tumor pathogenesis. This study was to investigate the role of miR-155-3p from M2 macrophages-derived exosomes (M2-Exo) in promoting medulloblastoma (MB) progression by mediating WD repeat domain 82 (WDR82). Methods miR-155-3p expression was detected by RT-qPCR. The relationship of miR-155-3p with clinicopathological features of MB patients was analyzed. M2-Exo were isolated and identified by TEM, NTA and Western blot. CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were performed to explore the role of miR-155-3p-enriched M2-Exo on the progression of MB cells. Luciferase assay were used to identify the relationship between miR-155-3p and WDR82. The effect of miR-155-3p-enriched M2-Exo on tumorigenesis of MB was confirmed by the xenograft nude mice model. Results miR-155-3p was up-regulated in MB tissues of patients and MB cell lines. High miR-155-3p expression was correlated with the pathological type and molecular subtype classification of MB patients. WDR82 was a direct target of miR-155-3p. miR-155-3p was packaged into M2-Exo. miR-155-3p-enriched M2-Exo promoted the progression of Daoy cells. miR-155-3p-enriched M2-Exo promoted in vivo tumorigenesis. Conclusion The study highlights that miR-155-3p-loaded M2-Exo enhances the growth of MB cells via down-regulating WDR82, which might provide a deep insight into MB mechanism.

Objective. To evaluate the changes of rectus abdominis thickness and inter-rectus distance before and after delivery with high-frequency ultrasound. Methods. A total of 148 pregnant women at 12 weeks of gestation who underwent prenatal examination in our hospital from January 2019 to March 2020 were selected, and 140 of them cooperated with rectus abdominis examination. According to the results of rectus abdominis examination 42 days after delivery, 97 patients were divided into the DRA group with rectus abdominis isolated and 43 patients were divided into the normal group with rectus abdominis not isolated. At 12 weeks, 24 weeks, and 37 weeks of pregnancy, 3 days and 42 days after delivery, the thickness and spacing of the left and right rectus abdominis muscle were measured by high-frequency ultrasound along the white linea at three positions: 5 cm above the navel, 3 cm below the umbilical edge, and 3 cm below the navel. Results. The thickness of rectus abdominis at 5 cm above the navel, 3 cm below the navel, and at the navel margin of the abdominal white line in the pregnant women of the two groups was gradually decreased with the increase of the pregnancy cycle and gradually recovered after delivery. At 42 days after delivery, the thickness of rectus abdominis in the DRA group was significantly lower than that in the normal group, which was 5 cm above the umbilicus, 3 cm below the umbilicus, and the umbilical margin of the abdominal white line ( P < 0.05 ). The space between rectus abdominis 5 cm above the navel, 3 cm below the navel, and the navel margin of the abdominal white line in the pregnant women of the two groups was gradually increased with the increase of the pregnancy cycle and gradually recovered after delivery. At 37 weeks of pregnancy, 3 days after delivery, and 42 days after delivery, the space of rectus abdominis along the umbilicus 5 cm above, 3 cm below the umbilicus, and the umbilicus border of the abdominal white line in the DRA group was significantly larger than that of the normal group ( P < 0.05 ). Conclusion. Ultrasound can accurately measure the inter-rectus distance and rectus thickness, accurately evaluate the degree of DRA, and realize the one-stop evaluation from prenatal diagnosis and prediction to postpartum rehabilitation monitoring, so as to intervene during pregnancy and reduce the risk of postpartum DRA.