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Ipragliflozin-induced improvement of liver steatosis in obese mice may involve sirtuin signaling

World Journal of Hepatology 2020年第7期12卷 350-362页

作者： Takayoshi Suga Ken Sato Tatsuya Ohyama Sho Matsui takeshi Kobayashi Hiroki Tojima Norio Horiguchi Yuichi yamazaki Satoru Kakizaki Ayaka Nishikido Takashi Okamura Masanobu Yamada TadahiroKitamura Toshio Uraoka Department of Gastroenterology and Hepatology Gunma University Graduate School of MedicineMaebashi 371-8511GunmaJapan Metabolic Signal Research Center Institute for Molecular and Cellular RegulationGunma UniversityMaebashi 371-8512GunmaJapan Department of Medicine and Molecular Science Gunma Graduate School of MedicineMaebashi 371-8511GunmaJapan

BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic ***2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal ***2 inhibitors lower glucose levels independently of insulin action by facilitating urinary glucose *** SGLT2 inhibitor ipragliflozin has reportedly improved liver steatosis in animal models and clinical ***,the mechanisms by which SGLT2 inhibitors improve liver steatosis are not fully *** To investigate the ameliorative effects of ipragliflozin on liver steatosis and the mechanisms of these effects in obese *** We analyzed 8-wk-old male obese(ob/ob)mice that were randomly divided into a group receiving a normal chow diet and a group receiving a normal chow diet supplemented with ipragliflozin(3 mg/kg or 10 mg/kg)for 4 *** also analyzed their lean sex-matched littermates receiving a normal chow diet as another control group. Body weight and liver weight were evaluated, and liverhistology, immunoblotting, and reverse transcription-polymerase chain reactionanalyses were *** lipid accumulation was significantly ameliorated in ob/ob mice treatedwith 10 mg/kg ipragliflozin compared to untreated ob/ob mice irrespective ofbody weight changes. Ipragliflozin had no appreciable effects on hepatic oxidativestress-related gene expression levels or macrophage infiltration, but significantlyreduced hepatic interleukin-1β (IL-1β) mRNA expression levels. Ipragliflozinincreased both the mRNA and protein expression levels of sirtuin 1 (SIRT1) in theliver. The hepatic mRNA levels of peroxisome proliferator-activated receptor γcoactivator 1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα),and fibroblast growth factor-21 (FGF21) were also significantly higher inipragliflozin-treated ob/ob mice than in untreated ob/ob *** study suggests that the liver steatosis-ameliorati

关键词： Selective sodium glucose cotransporter 2 Nonalcoholic fatty liver disease Sirtuin 1 Peroxisome proliferator-activated receptorγcoactivator 1α Peroxisome proliferator-activated receptorα Fibroblast growth factor-21

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SD3, an Arabidopsis thaliana Homolog of TIM21, Affects Intracellular ATP Levels and Seedling Development

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Molecular Plant 2012年第2期5卷 461-471页

作者： Hidefumi Hamasaki takeshi Yoshizumi Naoki Takahashi Mieko Higuchi Takashi Kuromori Yuko Imura Hiroaki Shimada Minami Matsui Plant Functional Genomics Research Group Plant Science Center RIKEN Yokohama Institute 1-7-22 Suehiro-cho Tsurumi-ku Yokohama Kanagawa 230-0045 Japan Department of Biological Science and Technology Tokyo University of Science 2641 Yamazaki Noda Chiba 278-8510 Japan Gene Discovery Research Group RIKEN Plant Science Center RIKEN Yokohama Institute 1-7-22 Suehiro-cho Tsurumi-ku Yokohama Kanagawa 230-0045 Japan

It is poorly understood how plants control their growth by cell division, elongation, and differentiation. We have characterized a seedling-lethal mutant segregation distortion 3 （sd3） that showed a very dwarf phenotype when grown in the light and, in the dark, had short hypocotyls with reduced ploidy levels. The corresponding gene of SD3 encodes a protein with high similarity to yeast translocase on the inner mitochondrial membrane 21 （TIM21）, which is a component of the TIM23 complex. Indeed, SD3 protein fused to GFP localized in the mitochondria. SD3 overexpression increased cotyledon size in the light and hypocotyl thickness in the dark. The expression of genes for several subunits of the respiratory-chain complexes III and IV was up-regulated in SD3-overexpressing plants. Furthermore, these plants showed high levels of ATP whereas those of sd3 were low. These results suggested that SD3 induced an increase in cell size by raising the expression of the respiratory-chain subunit genes and hence increased the intracellular ATP levels, We propose that intracellular ATP levels regulated by mitochondria control plant organ size.

关键词： hypocotyl elongation endoreduplication mitochondria ATR

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The Relationship between Neck and Shoulder Pain and the Sagittal Alignment of the Spine in Standing in Younger Generation

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Open Journal of Orthopedics 2015年第11期5卷 337-344页

作者： Tomonori Kenmoku Takane Suzuki Nobuyasu Ochiai Tatsuki Ebata Genyo Miyajima Naoshige Nagura Mitsufumi Nakawaki Ryo Tazawa Sho Hiramatsu Hironori yamazaki Yu Sasaki takeshi Yamaguchi Eiko Hashimoto Kenji Onuma Naonobu Takahira Kazuhisa Takahashi Masashi Takaso Department of Orthopedic Surgery Kitasato University School of Medicine Sagamihara Japan Sakura Orthopaedic Hospital Sakura Japan Department of Bioenvironmental Medicine Graduate School of Medicine Chiba Japan Department of Orthopaedic Surgery Chiba University Graduate School of Medicine Chiba Japan Department of Orthopedic Surgery Kitasato Medical Center Kitamoto Japan School of Allied Health Science Kitasato University Sagamihara Japan

Background: The relationship between chronic neck and shoulder pain and posture remains controversial. The purpose of this study was to investigate the relationship between chronic neck and shoulder pain and spinal sagittal alignment in standing posture in younger generation. Methods: Subjects included 57 females and 32 males (average age, 29.9 ± 5.7 years). All subjects were 20s or 30s. Spinal curvature was assessed using SpinalMouse. The subjects were also divided into a normal group (VAS zero group) and a pain group by VAS results. Statistical analysis was performed by Student’s t-test. Significance was defined as p < 0.05. Results: The normal group and pain group included 29 and 60 subjects, respectively. In terms of location of pain, thirty-one subjects felt neck pain, 50 felt pain above the scapula, and 17 felt pain between the thoracic spine and scapula. Thoracic kyphosis and lumbar lordosis in the pain group were significantly higher than those in the normal group (p = 0.013 and p = 0.020, respectively). Thoracic kyphosis in subjects with neck pain or pain above scapula was significantly higher than that in subjects without pain (p = 0.0075 and p = 0.025, respectively). Lumbar lordosis in subjects with pain above the scapula or interscapula was significantly higher than that in subjects without pain (p = 0.016).

关键词： Choronic Neck and Shoulder Pain Sagittal Alignment of the Spine Thoracic Kyphosis Lumber Lordosis

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