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Inhibition of gamma-glutamylcyclotransferase (GGCT), which is highly expressed in various cancer tissues, exerts anticancer effects both in vitro and in vivo. Previous studies have shown that depletion of GGCT blocks the growth of MCF7 breast cancer cells via upregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21); in addition, induction of autophagy plays a role in the upregulation of p21 upon GGCT knockdown. However, the mechanisms underlying induction of p21 in cancer cells are not fully understood. Here, we show that GGCT knockdown in PC3 human prostate cancer and A172 glioblastoma cells upregulates the mRNA and nuclear protein levels of Forkhead box O transcription factor 3a (FOXO3a), a transcriptional factor involved in tumor suppression. Simultaneous knockdown of FOXO3a and GGCT in PC3 and A172 cells attenuated upregulation of p21, followed by growth inhibition and cell death. Furthermore, simultaneous knockdown of GGCT and AMP-activated protein kinase (AMPK) α, a metabolic stress sensor, in PC3 and A172 cells led to marked attenuation of cellular responses induced by GGCT knockdown, including an increase in FOXO3a phosphorylation at Ser413, upregulation of p21, growth inhibition, and cell death. These results indicate that the AMPK–FOXO3a–p21 axis plays an important role in inhibition of cancer cell growth by depletion of GGCT.

In Japan veterinary antimicrobials are used most in the pig production sector. However, there is a paucity of data on the quantity of antimicrobials used on pig farms in Japan. This study describes antimicrobial use on Japanese pig farms in 2015, 2016 and 2017 in terms of mg of active ingredient per kg of PCU (population correction unit). Data on antimicrobial use from a total of 72 farrow-to finish farms over these three years were used in the study. The results revealed that the average use of antimicrobials in 2015, 2016 and 2017 was 304.8 (SD = 226.3), 311.2 (SD = 241.0) and 342.9 (SD = 291.3) mg/kg PCU, respectively. Most (97%) of the antimicrobials were administered orally. The most commonly used antimicrobials were tetracyclines, followed by macrolides, penicillins and sulfonamides. Tohoku was the region in which the lowest quantities of antimicrobial were used whilst South Kanto was the region in which the largest amount was used. The use of antimicrobials was on the increase in the North Kanto, South Kanto and Kyushu regions.