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The Kampo medicine Yokukansan (YKS) has a wide variety of properties such as anxiolytic, anti-inflammatory and analgesic effects, and is also thought to regulate tumor suppression. In this study, we investigated the anti-tumor effect of YKS. We used Lewis lung carcinoma (LLC)-bearing mice that were fed food pellets containing YKS and then performed a fecal microbiota analysis, a microarray analysis for microRNAs (miRNAs) and an in vitro anti-tumor assay. The fecal microbiota analysis revealed that treatment with YKS partly reversed changes in the microbiota composition due to LLC implantation. Furthermore, a miRNA array analysis using blood serum showed that treatment with YKS restored the levels of miR-133a-3p/133b-3p, miR-1a-3p and miR-342-3p following LLC implantation to normal levels. A TargetScan analysis revealed that the epidermal growth factor receptor 1 (EGFR1) signaling pathway is one of the major target pathways for these miRNAs. Furthermore, treatment with YKS restored the levels of miR-200b-3p and miR-200c-3p, a recognized mediator of cancer progression and controller of emotion, in the hypothalamus of mice bearing LLC. An in vitro assay revealed that a mixture of pachymic acid, saikosaponins a and d and isoliquiritigenin, which are all contained in YKS, exerted direct and additive anti-tumor effects. The present findings constitute novel evidence that YKS may exert an anti-tumor effect by reversing changes in the fecal microbiota and miRNAs circulating in the blood serum and hypothalamus, and the compounds found in YKS could have direct and additive anti-tumor effects.

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This study examined the characteristics of lower limb muscle activity in elderly persons after ergometric pedaling exercise for 1 month. To determine the effect of the exercise, surface electromyography (SEMG) of lower limb muscles was subjected to Daubechies-4 wavelet transformation, and mean wavelet coefficients were compared with the pre-exercise coefficients and the post-exercise coefficients in each wavelet level. The characteristics of muscle activity after pedaling exercise were also compared between the elderly subjects and young subjects. For the elderly subjects, the mean wavelet coefficients were significantly decreased in the tibialis anterior and the gastrocnemius medialis at wavelet levels of 3, 4, and 5 (125–62.5, 62.5–31.25, and 31.25–15.625 Hz, respectively), by pedaling exercise. However, the mean power of wavelet levels of 2 and 3 (250–125 and 125–62.5 Hz) within the rectus femoris and the biceps femoris were significantly increased in the young subjects. The effect of pedaling exercise is different from the effects of heavy-resistance training. It was suggested that the muscle coordination, motor unit (MU) firing frequency, and firing fiber type of lower limb muscles are changed with the different characteristics between elderly and young persons by pedaling exercise for 1 month.