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11.
Toshihiro Kimura Satoshi Fukushima Etsuko Okada Haruka Kuriyama Hisashi Kanemaru Mina Kadohisa‐Tsuruta Yosuke Kubo Satoshi Nakahara Aki Tokuzumi Ikko Kajihara Katsunari Makino Azusa Miyashita Jun Aoi Takamitsu Makino Hirotake Tsukamoto Yasuharu Nishimura Takashi Inozume Rong Zhang Yasushi Uemura Satoru Senju Hironobu Ihn 《Pigment cell & melanoma research》2020,33(5):744-755
Immune checkpoint inhibitors improved the survival rate of patients with unresectable melanoma. However, some patients do not respond, and variable immune‐related adverse events have been reported. Therefore, more effective and antigen‐specific immune therapies are urgently needed. We previously reported the efficacy of an immune cell therapy with immortalized myeloid cells derived from induced pluripotent stem cells (iPS‐ML). In this study, we generated OX40L‐overexpressing iPS‐ML (iPS‐ML‐Zsgreen‐OX40L) and investigated their characteristics and in vivo efficacy against mouse melanoma. We found that iPS‐ML‐Zsgreen‐OX40L suppressed the progression of B16‐BL6 melanoma, and prolonged survival of mice with ovalbumin (OVA)‐expressing B16 melanoma (MO4). The number of antigen‐specific CD8+ T cells was higher in spleen cells treated with OVA peptide‐pulsed iPS‐ML‐Zsgreen‐OX40L than in those without OX40L. The OVA peptide‐pulsed iPS‐ML‐Zsgreen‐OX40L significantly increased the number of tumor‐infiltrating T lymphocytes (TILs) in MO4 tumor. Flow cytometry showed decreased regulatory T cells but increased effector and effector memory T cells among the TILs. Although we plan to use allogeneic iPS‐ML in the clinical applications, iPS‐ML showed the tumorgenicity in the syngeneic mice model. Incorporating the suicide gene is necessary to ensure the safety in the future study. Collectively, these results indicate that iPS‐ML‐Zsgreen‐OX40L therapy might be a new method for antigen‐specific cancer immunotherapy. 相似文献
12.
Zolzaya Tumurgan Haruhiko Kanasaki Tuvshintugs Tumurbaatar Aki Oride Hiroe Okada Satoru Kyo 《Biochemistry and Biophysics Reports》2020
Hypothalamic kisspeptin, encoded by the Kiss-1 gene, governs the hypothalamic-pituitary-gonadal axis by directly regulating the release of gonadotropin-releasing hormone. In this study, we examined the roles of activin, inhibin, and follistatin in the regulation of Kiss-1 gene expression using primary cultures of fetal rat neuronal cells, which express the Kiss-1 gene and kisspeptin. Stimulation with activin significantly increased Kiss-1 gene expression in these cultures by 2.02 ± 0.39-fold. In contrast, a significant decrease in Kiss-1 gene expression was observed with inhibin A and follistatin treatment. Inhibin B did not modulate Kiss-1 gene expression. Activin, inhibin, and follistatin were also expressed in fetal rat brain cultures and their expression was controlled by estradiol (E2). The inhibin α, βA, and βB subunits were upregulated by E2. Similarly, follistatin gene expression was significantly increased by E2 in these cells. Our results suggest the possibility that activin, inhibin, and follistatin expressed in the brain participate in the E2-induced feedback control of the hypothalamic-pituitary-gonadal axis. 相似文献
13.
Takaaki Oteki Sohji Nagase Homare Shimohata Aki Hirayama Atsushi Ueda Hidekatsu Yokoyama 《Free radical research》2013,47(2):154-161
It is well known that oxidative stress is related to the pathogenesis of adriamycin (ADR) nephropathy. However, it is unclear how nitric oxide (NO) is associated with the pathophysiological process after ADR administration. The NO level in a kidney homogenate was assayed by electron paramagnetic resonance (EPR) spectrometry using a direct in vivo NO trapping technique after ADR administration. N-(3-(aminomethyl)benzyl)acetamidine (1400W) was used as a specific, inducible nitric oxide synthase (iNOS) inhibitor. The levels of NO after ADR administration gradually increased for 6 h and then decreased until 24 h after ADR administration. The fractional excretion of Na (FENa) in the urine was elevated in the ADR group on day 1. Pre-treatment of the animals with 1400W attenuated the increase in NO levels despite further elevation of FENa. These findings suggest that iNOS-derived NO does not produce a harmful effect but rather protects the ADR-treated kidney against sodium excretion. 相似文献
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Florian Wilfling Huajin Wang Joel T. Haas Natalie Krahmer Travis J. Gould Aki Uchida Ji-Xin Cheng Morven Graham Romain Christiano Florian Fröhlich Xinran Liu Kimberly K. Buhman Rosalind A. Coleman Joerg Bewersdorf Robert V. Farese Tobias C. Walther 《Developmental cell》2013,24(4):384-399
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Maki Seki Osamu Tsuruta Ryo Tatsumi Aki Soejima 《Bioorganic & medicinal chemistry letters》2013,23(14):4230-4234
A novel series of pyrrolidine derivatives as Na+ channel blockers was synthesized and evaluated for their inhibitory effects on neuronal Na+ channels. Structure–activity relationship (SAR) studies of a pyrrolidine analogue 2 led to the discovery of 5e as a potent Na+ channel blocker with a low inhibitory action against human ether-a-go-go-related gene (hERG) channels. Compound 5e showed remarkably neuroprotective activity in a rat transient middle cerebral artery occlusion (MCAO) model, suggesting that 5e would act as a neuroprotectant for ischemic stroke. 相似文献
18.
Yosuke Inoue Andrew Stickley Aki Yazawa Takeo Fujiwara Katsunori Kondo Naoki Kondo 《Chronobiology international》2016,33(4):441-447
Month of birth (MOB) has been linked to a variety of health conditions in adulthood. This study examined the association between MOB and mortality among the healthy elderly in Japan, where a practice of traditional age reckoning was employed up until the late 1940s. The results showed male participants born in December were more likely to die earlier while those born in January had lower mortality. It is possible that social factors in early life, such as the time period when a birth is officially registered, may have implications for health that stretch across the life course. 相似文献
19.
Heme Orientation of Cavity Mutant Hemoglobins (His F8 → Gly) in Either α or β Subunits: Circular Dichroism, 1H NMR,and Resonance Raman Studies
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Masako Nagai Yukifumi Nagai Yayoi Aki Hiroshi Sakurai Naoki Mizusawa Takashi Ogura Teizo Kitagawa Yasuhiko Yamamoto Shigenori Nagatomo 《Chirality》2016,28(8):585-592
Native human adult hemoglobin (Hb A) has mostly normal orientation of heme, whereas recombinant Hb A (rHb A) expressed in E. coli contains both normal and reversed orientations of heme. Hb A with the normal heme exhibits positive circular dichroism (CD) bands at both the Soret and 260‐nm regions, while rHb A with the reversed heme shows a negative Soret and decreased 260‐nm CD bands. In order to examine involvement of the proximal histidine (His F8) of either α or β subunits in determining the heme orientation, we prepared two cavity mutant Hbs, rHb(αH87G) and rHb(βH92G), with substitution of glycine for His F8 in the presence of imidazole. CD spectra of both cavity mutant Hbs did not show a negative Soret band, but instead exhibited positive bands with strong intensity at the both Soret and 260‐nm regions, suggesting that the reversed heme scarcely exists in the cavity mutant Hbs. We confirmed by 1H NMR and resonance Raman (RR) spectroscopies that the cavity mutant Hbs have mainly the normal heme orientation in both the mutated and native subunits. These results indicate that the heme Fe‐His F8 linkage in both α and β subunits influences the heme orientation, and that the heme orientation of one type of subunit is related to the heme orientation of the complementary subunits to be the same. The present study showed that CD and RR spectroscopies also provided powerful tools for the examination of the heme rotational disorder of Hb A, in addition to the usual 1H NMR technique. Chirality 28:585–592, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
20.
Koyama Satoshi Fujita Hiroyuki Shimosato Takeshi Kamijo Aki Ishiyama Yasufumi Yamamoto Eri Ishii Yoshimi Hattori Yukako Hagihara Maki Yamazaki Etsuko Tomita Naoto Nakajima Hideaki 《Probiotics and antimicrobial proteins》2019,11(1):295-298
Probiotics and Antimicrobial Proteins - Probiotic-rich foods are consumed without much restriction. We report here, a case of septic shock caused by yogurt derived Lactobacillus species in a... 相似文献