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Efficacy of probiotics on the modulation of gut microbiota in the treatment of diabetic nephropathy

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World Journal of Diabetes 2022年第3期13卷 150-160页

作者： Nozomi Nagase Yuka Ikeda Ai Tsuji Yasuko Kitagishi satoru matsuda Department of Food Science and Nutrition Nara Women's UniversityNara 630-8506Japan

Diabetic nephropathy(DN)is a major cause of end-stage renal disease,and therapeutic options for preventing its progression are insufficient.The number of patients with DN has been increasing in Asian countries because of westernization of dietary lifestyle,which may be associated with the following changes in gut microbiota.Alterations in the gut microbiota composition can lead to an imbalanced gastrointestinal environment that promotes abnormal production of metabolites and/or inflammatory status.Functional microenvironments of the gut could be changed in the different stages of DN.In particular,altered levels of short chain fatty acids,D-amino acids,and reactive oxygen species biosynthesis in the gut have been shown to be relevant to the pathogenesis of the DN.So far,evidence suggests that the gut microbiota may play a key role in determining networks in the development of DN.Interventions directing the gut microbiota deserve further investigation as a new protective therapy in DN.In this review,we discuss the potential roles of the gut microbiota and future perspectives in the protection and/or treatment of kidneys.

关键词： Diabetic nephropathy Short chain fatty acids Superoxide dismutase Reactive oxygen species D-amino acids Gut microbiota Diabetes mellitus Renal disease

Secretome-microRNA and anti-proliferative APRO family proteins as cancer prevention and stem cell research strategies

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BIOCELL 2022年第5期46卷 1163-1167页

作者： YUKA IKEDA NOZOMI NAGASE AI TSUJI KURUMI TANIGUCHI YASUKO KITAGISHI satoru matsuda Department of Food Science and Nutrition Nara Women’s UniversityNara630-8506Japan

Stemness of cancer cells contains limitless self-renewal proliferation.For the purpose of proliferation,secretome might exert its effects via the paracrine signaling.Specific microRNAs enclosed in the secretome of cancer stem cells could regulate the expression of anti-proliferative APRO family proteins.The biological functions of APRO family proteins seems to be quite intricate,however,which might be a key modulator of microRNAs,then could regulate the proliferation of cancer cells.In addition to affecting proliferation/differentiation during cellular development,APRO family proteins might also play an imperious role on keeping homeostasis in healthy stem cells under a physiological condition.Therefore,relationship between the microRNAs and the APRO family proteins has attracted much attention in the field of cancer research and regenerative medicine.Here,we have described the molecular mechanism behind this interplay that have a potential role in the future promising tools with targeting APRO family proteins for the medical applications.

关键词： Cancer Stem cell Secretome Proliferation APRO family microRNA

Z-shaped incision without epithelial resection in pterygium surgery

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1262-1266页

作者： satoru Kase Shinki Chin Susumu Ishida Department of Ophthalmology Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporo 060-8638Japan

AIM:To introduce a novel surgical technique using a Z-shaped incision without epithelial resection in ophthalmic pterygia.METHODS:This was a prospective study.During pterygium surgery,all proliferative tissues were separated from the cornea and conjunctiva without resection of the tissues.The unaffected conjunctiva was incised in a Z-shape.The upper(or lower)conjunctival flap was sutured to the lower(or upper)normal conjunctiva on the limbal sclera,while the proliferative tissue was sutured to the upper conjunctiva(or lower)near the fornix.RESULTS:Ten patients with pterygia were eligible for this study.Eight patients with primary pterygia and 2 with recurrent pterygia were included.The age of patients at surgery ranged from 47 to 90y(average:71.9y).Five patients each showed right and left-sided pterygia.The postoperative follow-up periods were from 8 to 78mo(average:25.0mo).The surgery was successfully conducted and wounds were favorably reconstructed in all patients.The proliferative tissues sutured to the normal conjunctiva showed palor and attenuated neovessles,and never showed re-growth after surgery.Nine patients did not show recerrence.Recerrent pterygium was noted in 1 patient,but additional treatments were not required.CONCLUSION:The procedure involves the reconstruction of pterygial tissue and normal conjunctiva using a Z-shaped incision.The scleral limbal wound can be covered with nonaffected conjunctiva without any excision of conjunctival epithelia in patients with primary or recurrent pterygia.

关键词： pterygium surgery Z-shape non-resection

Association of anastomotic leakage with long-term oncologic outcomes of patients with esophagogastric junction cancer

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World Journal of Gastrointestinal Surgery 2022年第1期14卷 46-55页

作者： Masashi Takeuchi Hirofumi Kawakubo satoru matsuda Shuhei Mayanagi Tomoyuki Irino Jun Okui Kazumasa Fukuda Rieko Nakamura Norihito Wada Hiroya Takeuchi Yuko Kitagawa Department of Surgery Keio University School of MedicineTokyo 160-8582Japan Department of Preventive Medicine and Public Health Keio University School of MedicineTokyo 160-8582Japan Department of Surgery Hamamatsu University School of MedicineShizuoka 431-3192Japan

BACKGROUND Despite improvements in surgical procedures and peri-operative patients management,the postoperative complications in esophagogastric junction(EGJ)cancer remain high because of technical aspects.Several studies have indicated the negative influence of postoperative infectious complications on long-term survival after gastrointestinal surgery.However,no study has shown the association between postoperative complications and long-term survival of patients with EGJ cancer.AIM To elucidate influence of postoperative complications on the long-term outcomes of patients with EGJ cancer.METHODS A total of 122 patients who underwent surgery for EGJ cancer at the Keio University were included in this study.We examined the association between complications and long-term oncologic outcomes.RESULTS In all patients,the 3-year overall survival(OS)rate was 71.9%,and the recurrencefree survival(RFS)rate was 67.5%.Compared with patients without anastomotic leakage,those with anastomotic leakage had poor median OS(8 mo vs not reached,P=0.028)and median RFS(5 mo vs not reached,P=0.055).Among patients with cervical anastomosis,there were not significant differences between patients with and without anastomotic leakage.However,among patients who underwent intrathoracic anastomosis,patients with anastomotic leakage had significantly worse OS(P=0.002)and RFS(P=0.005).CONCLUSION Anastomotic leakage was significantly associated with long-term oncologic outcomes of patients with EGJ cancer,especially those who underwent intrathoracic anastomosis.Cervical anastomosis with subtotal esophagectomy may be an option for the patients who are at high risk for anastomotic leakage.

关键词： Esophagogastric junction cancer Complication Long-term outcome

Improvement of histone deacetylase inhibitor efficacy by SN38 through TWIST1 suppression in synovial sarcoma

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Cancer Innovation 2024年第2期3卷 80-95页

作者： satoru Sasagawa Jun Kumai Toru Wakamatsu Yoshihiro Yui Molecular Biology Laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Sarcoma Treatment Laboratory Research InstituteNozaki Tokushukai HospitalDaitoOsakaJapan Department of Musculoskeletal Oncology Service Osaka International Cancer InstituteOsakaJapan

Background:Synovial sarcoma(SS)is an SS18-SSX fusion gene-driven soft tissue sarcoma with mesenchymal characteristics,associated with a poor prognosis due to frequent metastasis to a distant organ,such as the lung.Histone deacetylase(HDAC)inhibitors(HDACis)are arising as potent molecular targeted drugs,as HDACi treatment disrupts the SS oncoprotein complex,which includes HDACs,in addition to general HDACi effects.To provide further molecular evidence for the advantages of HDACi treatment and its limitations due to drug resistance induced by the microenvironment in SS cells,we examined cellular responses to HDACi treatment in combination with two-dimensional(2D)and 3D culture conditions.Methods:Using several SS cell lines,biochemical and cell biological assays were performed with romidepsin,an HDAC1/2 selective inhibitor.SN38 was concomitantly used as an ameliorant drug with romidepsin treatment.Cytostasis,apoptosis induction,and MHC class I polypeptide-related sequence A/B(MICA/B)induction were monitored to evaluate the drug efficacy.In addition to the conventional 2D culture condition,spheroid culture was adopted to evaluate the influence of cell-mass microenvironment on chemoresistance.Results:By monitoring the cellular behavior with romidepsin and/or SN38 in SS cells,we observed that responsiveness is diverse in each cell line.In the apoptotic inducible cells,co-treatment with SN38 enhanced cell death.In nonapoptotic inducible cells,cytostasis and MICA/B induction were observed,and SN38 improved MICA/B induction further.As a novel efficacy of SN38,we revealed TWIST1 suppression in SS cells.In the spheroid(3D)condition,romidepsin efficacy was severely restricted in TWIST1-positive cells.We demonstrated that TWIST1 downregulation restored romidepsin efficacy even in spheroid form,and concomitant SN38 treatment along with romidepsin reproduced the reaction.Conclusions:The current study demonstrated the benefits and concerns of using HDACi for SS treatment in 2D and 3D culture conditions and provided molecular evi

关键词： HDAC inhibitor MICA/B SN38 spheroid synovial sarcoma TWIST1

Current status and challenges in sentinel node navigation surgery for early gastric cancer

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Chinese Journal of Cancer Research 2021年第2期33卷 150-158页

作者： satoru matsuda Tomoyuki Irino Hirofumi Kawakubo Hiroya Takeuchi Yuko Kitagawa Department of Surgery Keio University School of MedicineTokyo 160-8582Japan Department of Surgery Hamamatsu University School of MedicineShizuoka 431-3192Japan

As an optimal surgical procedure to accurately evaluate lymph node(LN)metastasis during surgery with minimal surgical resection,we have been developing sentinel node(SN)biopsy for early gastric cancer since the 1990s.Twelve institutions from the Japanese Society of Sentinel Node Navigation Surgery(SNNS),including Keio University Hospital,conducted a multicenter prospective trial to validate the SN concept using the dual-tracer method with blue dye and a radioisotope.According to the results,397 patients were included in the final analysis,and the overall accuracy in detecting LN metastasis using SN biopsy was 99%(383 of 387).Based on the validation study,we are targeting cT1N0 with a primary tumor of≤4 cm in diameter as an indication for SN biopsy for gastric cancer.We are currently running a multicenter nonrandomized phaseⅢtrial to assess the safety and efficacy of SN navigation surgery.The Korean group has reported the result of a multicenter randomized phaseⅢtrial.Since meticulous gastric cancer in the remnant stomach was rescued by subsequent gastrectomy,the disease-specific survival was comparable between the two techniques,implying that SN navigation surgery can be an alternative to standard gastrectomy.With the development of SN biopsy procedure and treatment modalities,the application of SN biopsy will be expanded to achieve an individualized minimally invasive surgery.

关键词： Sentinel node gastric cancer minimally invasive surgery

By using either endogenous or transplanted stem cells,which could you prefer for neural regeneration？

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Neural Regeneration Research 2018年第10期13卷 1731-1732页

作者： satoru matsuda yukie nakagawa kumi amano yuka ikeda ai tsuji yasuko kitagishi department of food science and nutrition nara women's University Kita—Uoya Nishimachi Nara Iapa

Neural regeneration by stem cells transplantation：Tissue regeneration and homeostasis are principally dependent on tissue stem cells which possess abilities of self-renewal and differentiation into multidirectional specialized cell types.In general,stem cells are critical for normal tissue renewal as well as repair after tissue injury.For example,mesenchymal stromal cells and endothelial progenitor cells identified in bone marrow could.

关键词： SPINAL-CORD-INJURY ISCHEMIA

Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation

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World Journal of Hematology 2023年第2期10卷 15-24页

作者： Sayuri Yoshikawa Kurumi Taniguchi Haruka Sawamura Yuka Ikeda Ai Tsuji satoru matsuda Food Science and Nutrition Nara Women's UniversityNara 630-8506Japan

Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.

关键词： Gut microbiota Hematopoietic stem cell Reactive oxygen species Allogeneic hematopoietic stem cell transplantation Graft vs host disease Gut-immune axis©The Author(s)2023.Published by Baishideng Publishing Group Inc.All rights reserved.

High-density circulating fluidized bed gasifier for advanced IGCC/IGFC-Advantages and challenges

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Particuology 2010年第6期8卷 602-606页

作者： Guoqing Guan Chihiro Fushimi Atsushi Tsutsumi Masanori Ishizuka satoru matsuda Hiroyuki Hatano Yoshizo Suzuki Collaborative Research Center for Energy Engineering Deportment of Mechanical and Biolhnctional Systems Institute of Industrial Science The University of Tokyo 4-6-1 Komaba Meguoro-ku Tokyo 153-8505Japan Clean Gas Group National Institute of Advanced Industrial Science and Technology 16- 1 Onogawa Tsukuba Iboraki 305-8569Japan

Coal-fired Integrated Gasification Combined Cycle （IGCC） and Integrated coal Gasification Fuel-cell Com- bined cycle （IGFC） are being developed as high-efficiency electric power generation technology. However, the highest theoretical gross thermal efficiency of the conventional IGCC]IGFC is still below 52~. In order to obtain higher power generation efficiency, an advanced IGCC （A-IGCC） or advanced IGFC （A-IGFC） sys- tem making use of the exergy recuperation concept by recycling waste heat from gas turbine or fuel cells for steam gasification of coal and biomass was proposed in our laboratory, Corresponding to this system, a novel high-density triple-bed combined circulating fluidized bed （TBCFB） gasifier, composed of a downer pyrolyzer, a bubbling fluidized bed char gasifier, and a riser combustor, was proposed to replace traditional gasifiers such as the entrained flow bed gasifier. The new system is expected to more effectively utilize the waste heat from gas turbines or fuel cells and the heat produced by the combustion of the unreacted char in the riser combustor for pyrolysis and gasification of coal and biomass. In this short review, the advantages and future challenges in the development of high-density TBCFB gasifier are presented and discussed.

关键词： IGCC/IGFC High-density circulating fluidized bed Gasifier Riser Downer Bubbling fluidized bed Exergy recuperation Biomass Coal