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Gene-activated matrix harboring a miR20a-expressing plasmid promotes rat cranial bone augmentation

Regenerative Biomaterials 2021年第2期8卷 34-42页

作者： Rena Shido Yoshinori Sumita Masahito Hara Mayumi Iwatake Shun Narahara Mayumi Umebayashi Kei-ichiro Miura Yukinobu Kodama izumi asahina Department of Regenerative Oral Surgery Unit of Translational MedicineNagasaki University Graduate School of Biomedical Sciences1-7-1 SakamotoNagasaki 852-8588Japan Basic&Translational Research Center for Hard Tissue Disease Unit of Translational MedicineNagasaki University Graduate School of Biomedical Sciences1-7-1 SakamotoNagasaki 852-8588Japan Laboratory of Craniofacial Tissue Engineering and Stem Cells Faculty of DentistryMcGill University3640 University StreetM43MontrealQuebec H3A 2B2Canada Department of Hospital Pharmacy Nagasaki University Hospital1-7-1 SakamotoNagasaki 852-8501Japan

Gene-activated matrix(GAM)has a potential usefulness in bone engineering as an alternate strategy for the lasting release of osteogenic proteins but efficient methods to generate non-viral GAM remain to be *** this study,we investigated whether an atelocollagen-based GAM containing naked-plasmid(p)DNAs encoding microRNA(miR)20a,which may promote osteogenesis in vivo via multiple pathways associated with the osteogenic differentiation of mesenchymal stem/progenitor cells(MSCs),facilitates rat cranial bone ***,we confirmed the osteoblastic differentiation functions of generated pDNA encoding miR20a(pmiR20a)in vitro,and its transfection regulated the expression of several of target genes,such as Bambi1 and PPARc,in rat bone marrow MSCs and induced the increased expression of ***,when GAMs fabricated by mixing 100 ll of 2%bovine atelocollagen,20mg b-TCP granules and 0.5mg(3.3 lg/ll)AcGFP plasmid-vectors encoding miR20a were transplanted to rat cranial bone surface,the promoted vertical bone augmentation was clearly recognized up to 8 weeks after transplantation,as were upregulation of VEGFs and BMP4 expressions at the early stages of ***,GAM-based miR delivery may provide an alternative non-viral approach by improving transgene efficacy via a small sequence that can regulate the multiple pathways.

关键词： gene-activated matrix in vivo gene transfer bone augmentation atelocollagen mir20a

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Diachronic changes in mouse tumor and fibrous tissue adjacent to mouse tumor subjected to photodynamic therapy

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中国口腔颌面外科杂志 2008年第B5期6卷 155-156页

作者： Masataka Uehara Takayoshi Tobita Seigo Ohba Mihoko Nonaka izumi asahina Department of Regenerative Oral Surgery Unit of TranslationalMedicine Graduate School of Biomedical Sciences NagasakiUniversity. Nagasaki 852-8588 Japan

Photodynamic therapy (PDT) as a cancer treatment consist of the systemic administration of a photosensitizer and laser irradiation. PDT is an effective treatment to control local cancer lesions. However, recurrence of the tumor after PDT remains problematic in spite of a good initial response. Hence, PDT must be repeatedly administered for efficacy, and it is necessary to investigate the behavior of tumor cells that survive PDT. In the present study, the diachronic changes in residual tumor cells and fibrous tissue adjacent to tumor subjected to PDT were investigated in terms of morphometric analysis, proliferating cell nuclear antigen (PCNA) immunohistochemistry, vascular endothelial growth factor (VEGF) immunohistochemistry and heat shock protein 47 (HSP47) immunohistochemistry.A photosensitizer (hematoporphyrin oligomers) was injected intraperitoneally to mice bearing NR-S1 mouse squamous cell carcinoma in the dorsum 48 h before laser irradiation. Mice were sacrificed at intervals of 0, 0.5, 2.5, 6, 48 and 72 hours after PDT, and the tumors were excised. The morphometric changes of nuclei of the residual tumor cells after PDT were analyzed in hematoxylin and eosin staining specimens. Both nuclear area and coefficient of variation of the nuclear area were significantly lower in the experimental groups' nuclei than in control tumor nuclei at 24 and 48 hours after PDT. In the PCNA immunohistochemical staining, PCNA labeling index was the lowest at 24 hours after PDT. On the other hand, both of VEGF expression in the residual tumor cells and HSP47 expression in the fibrous tissue adjacent tumor were peak at 6 hours after PDT. Furthermore, procollagen type I was detected in the fibrous tissue adjacent to the tumor at 24 and 48 hours after PDT. VEGF is a specific endothelial cell growth factor, known to potentiate tumor growth and angiogenesis and it plays a well recognized and important role in metastasis. Accordingly, it would be reasonable to expect that VEGF induce

关键词：肿瘤纤维组织光力学治疗方法

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Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika Fujii Charles F.Zorumski Yukitoshi izumi Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

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Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

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Neural Regeneration Research 2024年第10期19卷 2212-2218页

作者： Yukitoshi izumi Kazuko A.O'Dell Charles F.Zorumski Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

关键词： cognitive impairment glyphosate microglia neuroinflammation roundup toll-like receptor 4 zinc chelation

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Oxygen uptake during the last bouts of exercise incorporated into high-intensity intermittent cross-exercise exceeds the V_ O2max of the same exercise mode

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Sports Medicine and Health Science 2024年第1期6卷 63-69页

作者： Yuzhong Xu Xin Liu Katsunori Tsuji Takafumi Hamaoka izumi Tabata Faculty of Sport and Health Science Ritsumeikan UniversityKusatsuShigaJapan

Oxygen uptake(V O_(2))was measured during a non-exhaustive high-intensity intermittent cross-exercise(HIICE)protocol consisting of four alternating bouts of 20 s running(R)and three bouts of bicycle exercise(BE)at~160%and~170%maximal oxygen uptake(V O_(2)max),respectively,with 10 s between-bout rests(sequence R-BE-R-BER-BE-R).The V O_(2) during the last BE([52.2±5.0]mL⋅kg^(-1)⋅min^(-1))was significantly higher than the V O_(2)max of the BE([48.0±5.4]mL⋅kg^(-1)⋅min^(-1),n=30)and similar to that of *** clarifying the underlying mechanisms,a corresponding HIICE-protocol with BE and arm cranking ergometer exercise(AC)was used(sequence AC-AC-BE-AC-BE-AC-AC-BE).In some experiments,thigh blood flow was occluded by a cuff around the upper *** occlusion,the V O_(2) during the AC([39.2±7.1]mL⋅kg^(-1)⋅min^(-1)[6th bout])was significantly higher than the V O_(2)max of AC([30.2±4.4]mL⋅kg^(-1)⋅min^(-1),n=7).With occlusion,the corresponding V O_(2)([29.8±3.9]mL⋅kg^(-1)⋅min^(-1))was reduced to that of the V O_(2)max of AC and significantly less than the V O_(2) without *** findings suggest that during the last bouts of HIICE may exceed the of the specific exercise,probably because it is a summation of the V O_(2) for the ongoing exercise plus excess post-oxygen consumption(EPOC)produced by the previous exercise with a higher V O_(2)max.

关键词： Maximal oxygen uptake Running Bicycle ergometer exercise Arm cranking ergometer exercise Cross-exercise Excess post-exercise oxygen consumption (EPOC) Tabata training

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A comparison of the efficacy of dutasteride on reducing lower urinary tract symptoms among patients with small versus large benign prostatic hyperplasia

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Current Urology 2024年第3期18卷 199-202页

作者： Kazuyoshi Shigehara Yuki Kato Shohei Kawaguchi Kouji izumi Yoshifumi Kadono Atsushi Mizokami Department of Urology Kanazawa University Graduate School of Medical ScienceKanazawaIshikawaJapan

Background Only a few reports have currently studied the efficacy of dutasteride in patients with small benign prostatic hyperplasia(BPH).We investigated the efficacy of dutasteride on reducing lower urinary tract symptoms among *** and methods A total of 81 patients with BPH who completed 52weeks of 0.5?mg dutasteride treatment were *** patient filled out the International Prostatic Symptom Score(IPSS)and overactive bladder symptom score(OABSS)at baseline and at the 6-and 12-month follow-up *** testosterone,prostate-specific antigen,adenoma/prostate volume(PV),uroflowmetry analysis,and postvoid residual volume were evaluated at baseline and at the 12-month follow-up *** enrolled patients were divided into 2 groups according to PV at *** groups were as follows:Group A(PV≥30 mL)and Group B(PV<30 mL).Results Groups A and B had mean PVs of 52.1 and 23.6 mL and mean IPSS scores of 16.7 and 14.4,*** A had significantly higher OABSS and prostate-specific antigen levels at baseline than Group B,while no significant differences in any other baseline characteristics was *** dutasteride treatment,adenoma volume and PV decreased significantly,while testosterone level showed a significant increase in both *** A showed significant improvements in the total IPSS,voiding and storage subscore of the IPSS,OABSS,maximum flow rate,and postvoid residual *** B,on the other hand,also showed significant improvements only in the total IPSS,voiding subscore of the IPSS,and maximum flow *** The present study suggests a possible beneficial effect of dutasteride treatment on the reduction of lower urinary tract symptoms in patients with small and large ***,the effectiveness of dutasteride was limited compared to patients with large BPH(PV≥30 mL).

关键词： Benign prostatic hyperplasia Dutasteride Lower urinary tract symptoms Testosterone Voiding dysfunction

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Perspectives of Science and Technology in Disaster Risk Reduction of Asia

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International Journal of Disaster Risk Science 2016年第4期7卷 329-342页

作者： Rajib Shaw Takako izumi Peijun Shi Integrated Research on Disaster Risks(IRDR) International Research Institute of Disaster Science(IRIDeS) Tohoku University State Key Laboratory of Earth Surface Processes and Resource Ecology Beijing Normal University

Science and technology innovation has always been present in Asia,but its application in disaster risk reduction(DRR) has been *** Asia,globally significant hotspots of disasters and economic development have emerged in which the application of science and technology in DRR has become an essential requirement for informed decision *** has supported establishment and implementation of major international initiatives in DRR,including the Hyogo Framework for Action *** more recent Sendai Framework for DRR 2015-2030 recognizes the importance of science and technology in all of its priority action areas,and subsequent global and regional forums and conferences have reconfirmed science and technology's *** perceive and monitor the progress of science and technology in DRR,a qualitative assessment of different countries is made using three major attributes:(1) science-based decision making;(2) investment in science and technology;and(3) the intensity of science's link to the *** assessment exercise points out several strengths and weaknesses in science and technology application;the method can be employed to develop future multistakeholder and multidisciplinary science and technology plans at the country *** implement regional and national activities,a set of 15 recommendations is put forward,which will strengthen the collective regional "science voice" in DRR.

关键词： DRR policy making Science innovation Science investment Sendai Framework Technology application

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Fabrication of a model specimen for understanding micro-galvanic corrosion at the boundary ofα-Mg andβ-Mg17Al12

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Journal of Magnesium and Alloys 2023年第1期11卷 137-153页

作者： Zheng Shao Masashi Nishimoto izumi Muto Yu Sugawara Department of Materials Science Graduate School of EngineeringTohoku University6-6-02 Aza-AobaAramakiAoba-kuSendai 980-0579Japan

A model specimen with a single boundary of theα/βphase simulating Mg-Al alloys was successfully fabricated by spark plasma sintering.A small electrode area ofαphase orβphase was prepared using the model specimen,and the OCPs(open-circuit potentials)of each phase and a small electrode area containing theα/βphase boundary in 0.1 M NaCl at pH 8.0 were compared:theβphase exhibited a higher potential,and theαphase showed a lower *** OCP of the small area containing theα/βphase boundary was the intermediate value of these *** a small area containingα/βphase boundary,discoloration and gas bubbles were observed on theαphase,but no bubble generation was detected on theβ*** gas bubbles were initially generated on theαphase near theβphase,but as the discoloration(corrosion)of theαphase approached theβphase,the bubbles were generated on theβ*** micro-galvanic corrosion of theαandβphases,theβphase did not always function as the preferred ***αphase partially corroded(or discolored)and became the anodes,so that the surrounding areas were most likely to be the *** corroded areas(anodes)in theαphase approached theβphase,theβphase would become *** addition to the micro-galvanic corrosion mechanism,the role of Al in corrosion resistance at theα/βphase boundary was determined by surface analysis.

关键词： Magnesium alloy α/βphase boundary Micro-scale observation technique Micro-galvanic corrosion Spark plasma sintering

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Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer: A case report

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World Journal of Gastroenterology 2006年第32期12卷 5237-5239页

作者： Susumu Kawate izumi Takeyoshi Yasuo Morishita Department of Thoracic and Visceral Organ Surgery Gunma University Graduate School of Medicine MaebashiGunma 371-8511Japan

We report for the first time the possibility of weekly paclitaxel chemotherapy for a patient with advanced, nonresectable gastric cancer undergoing hemodialysis. A 50-year-old man with chronic renal failure due to bilateral polycystic kidneys, who had undergone hemodialysis three times a week for 5 years, presented with hematemesis in December 2004. Based on the diagnosis of gastric cancer with lymph node metastases, surgery was performed. On the 15th postoperative day, the patient was treated with chemotherapy using paclitaxel. Paclitaxel was administered at a dose of 60 mg/m^2 as a 1 h iv infusion in 250 mL of saline. Hemodialysis was started 1 h after the completion of the paclitaxel infusion and was performed for 3 h. Paclitaxel was administered weekly on d 1, 8, and 15 on a 28-d cycle. The maximum plasma concentration of paclitaxel was 1390 μg/L. The area under the curve of paclitaxel was 4398.6 μg·h/L. Grade 2 leukopenia was encountered during the first cycle. The plasma concentrations of paclitaxel from 6 to over 24 h after the infusion were 0.01 to 0.1 μmol/L in our patient, and these concentrations have been shown to be effective on inhibiting the growth of gastric cancer cells without producing adverse side effects in the patient. The plasma concentration of paclitaxel was not influenced by hemodialysis. We conclude that the pharmacokinetics of paclitaxel is not altered in a patient with renal failure, and that weekly paclitaxel is a suitable treatment regimen for hemodialysis patients with advanced gastric cancer.

关键词： Paclitaxel Gastric cancer Hemodialysis

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Immediate-early Inducible Function in Upstream Region of junB Gene

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Biomedical and Environmental Sciences 2006年第3期19卷 210-213页

作者： HONG WAN HIROSHI ISHIHAR izumi TANAKA Beijing Neurosurgical Institute Beijing 100050 China National Institute of Radiological Sciences Chiba-shi 263-8555 Japan

Objective To analyze the upstream region of radiation-induced junB gene. Methods Four plasmids containing 250 bp, 590 bp, 900 bp and 1650 bp, and CAT reporter gene were constructed separately and introduced to L8704 cells. The cells were irradiated with 2 Gy X-rays and incubated at different intervals. Total RNA was extracted from the cells and fluctuation of the CAT mRNA level was assessed by the RNA ratio of CAT/β-actin measured by quantitative Northern blot hybridization. Results CAT mRNA expression containing 900 bp and 1560 bpjunB promoter remarkably and rapidly increased, and reached its peak 30min after 2 Gy X-my irradiation. Conclusions 590-900 bp fragments located in the upstream region of junB gene play an important role in the early process of cells against radiation.

关键词： junB promoter CAT reporter gene Immediate-early response gene Signal transduction

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