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Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin(Ⅳ) prodrug delivery and enhanced colorectal cancer therapy

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Chinese Chemical Letters 2024年第4期35卷 280-286页

作者： Wenjia Wang Xingyue He Xiaojie Wang Tiantian Zhao Osamu Muraoka Genzoh Tanabe Weijia Xie Tianjiao Zhou Lei Xing Qingri Jin Hulin Jiang State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Faculty of Pharmacy kinki univ.rsity HigashiosakaOsaka 577-8502Japan State Key Laboratory of Natural Medicines(SKLNM)and Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityNanjing 210009China School of Pharmacy Hangzhou Medical CollegeHangzhou 311399China College of Pharmacy Yanbian UniversityYanji 133002China

Oxaliplatin(Oxa) is the first-line chemotherapeutic drug for the treatment of colorectal cancer(CRC). However, long-term Oxa chemotherapy can induce inflammation and increase the levels of cyclooxygenase-2(COX-2) and prostaglandin E2(PGE2), which can promote tumor metastasis. Moreover,high glutathione(GSH) levels in CRC cells significantly reduce Oxa sensitivity and seriously restrict the clinical application of Oxa. Herein, an Oxa(Ⅳ) prodrug with anti-inflammatory properties(desmethyl naproxe, DN) and GSH-depleting cyclodextrin pseudo-polyrotaxane carriers were prepared and further self-assembled into micellar nanoparticles(designated DNPt@PPRI). The relesae of DN from DNPt@PPRI can reduce the level of PGE2 to inhibit inflammation and tumor metastasis by decreasing COX-2 protein,and also synergize with Oxa to inhibit tumor. More importantly, GSH depletion can reduce the detoxification of Oxa and further enhance chemotherapy-induced apoptosis. DNPt@PPRI have a good GSH depletion ability to enhance the sensitivity of Oxa, indicating a potential in the synergistic chemotherapy and chemo-sensitization of colorectal cancer.

关键词： Oxaliplatin Glutathione depletion Tetravalent platinum prodrug Synergistic therapy Colorectal cancer

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Carotenoid productivity in human intestinal bacteria Eubacterium limosum and Leuconostoc mesenteroides with functional analysis of their carotenoid biosynthesis genes

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Engineering Microbiology 2024年第2期4卷 1-11页

作者： Wataru Matsumoto Miho Takemura Haruka Nanaura Yuta Ami Takashi Maoka Kazutoshi Shindo Shin Kurihara Norihiko Misawa Research Institute for Bioresources and Biotechnology Ishikawa Prefectural University1-308SuematsuNonoich-shi 921-8836Japan Department of Science and Technology on Food Safety Kinki University930 NishimitaniKinokawaWakayama 649-6493Japan Research Institute for Production Development Shimogamo-morimotochoSakyo-kuKyoto 606-0805Japan Department of Food and Nutrition Japan Women’s UniversityMejirodaiBunkyo-kuTokyo 112-8681Japan

The human intestinal microbiota that comprise over 1,000 species thrive in dark and anaerobic *** are recognized for the production of diverse low-molecular-weight metabolites crucial to human health and ***,low-molecular-weight pigments known for their antioxidative activity,are delivered to humans through oral ***,it remains unclear whether human intestinal bacteria biosynthesize carotenoids as part of the in-situ *** this study,we investigated carotenoid synthesis genes in vari-ous human gut and probiotic *** a result,novel candidates,the crtM and crtN genes,were identified in the carbon monoxide-utilizing gut anaerobe Eubacterium limosum and the lactic acid bacterium Leuconostoc mesenteroides *** gene candidates were isolated,introduced into Escherichia coli,which synthesized a carotenoid substrate,and cultured *** analysis of the resulting carotenoids re-vealed that the crtM and crtN gene candidates of *** and *** mediate the production of 4,4′-diaponeurosporene through 15-cis-4,4′-*** of the crtE-homologous genes in these bacteria indicated their non-functionality for C40-carotenoid *** and ***,along with the known carotenogenic lactic acid bacterium Lactiplantibacillus plantarum,were observed to produce no carotenoids under strictly anaerobic *** two lactic acid bacteria synthesized detectable levels of 4,4′-diaponeurosporene under semi-aerobic *** findings highlight that the obligate anaerobe ***-sum retains aerobically functional C30-carotenoid biosynthesis genes,potentially with no immediate self-utility,suggesting an evolutionary direction in carotenoid biosynthesis.(229 words)

关键词： C_(30)carotenoid biosynthesis Obligate anaerobe Human gut bacterium Eubacterium limosum Leuconostoc mesenteroides Lactiplantibacillus plantarum

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Evaluation of thermal sprayed coating using ultrasonic inspection by means of bottom echo back reflection

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中国有色金属学会会刊：英文版 2009年第4期19卷 984-987页

作者： Toshifumi KUBOHORI Toru ITO Wahidul lah WAHI Yasuyuki INUI Toshiro IKUTA School of Science and Engineering Kinki University

Thermal spraying technique is widely used in various mechanical parts as a surface reforming ***,as demand to maintain superior mechanical performance in harsh operating environment increases,the need for non-destructive evaluation method for thermal spray coating becomes more *** this purpose,we thinned the thickness of the thermal sprayed coating by abrasion with blasting and used ultrasonic inspection by means of bottom echo reflection for effective measurement of abrasion quantity in thermal sprayed *** results obtained are summarized as *** the thickness of thermal sprayed coating becomes thin,the echo height *** is because thermal sprayed coatings absorb ultrasonic *** energy absorbed by Al2O3 is smaller compared with Fe-13Cr *** sprayed coatings submerged in water have a lower echo height compared with *** mentioned above,the thermal sprayed coating thickness can be estimated using ultrasonic inspection by means of bottom echo back reflection.

关键词：超声波检测热喷涂层评价方法声反射底部热喷涂涂层涂层厚度能量吸收

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Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph node metastases in pancreatobiliary carcinoma

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World Journal of Gastroenterology 2016年第12期22卷 3381-3391页

作者： Takeshi Miyata Masayuki Kitano Shunsuke Omoto Kumpei Kadosaka Ken Kamata Hajime Imai Hiroki Sakamoto Naoshi Nisida Yogesh Harwani Takamichi Murakami Yoshifumi Takeyama Yasutaka Chiba Masatoshi Kudo Department of Gastroenterology and Hepatology Kinki University Faculty of Medicine Department of Radiology Kinki University Faculty of Medicine Department of Surgery Kinki University Faculty of Medicine Division of Biostatistics Clinical Research Center Kinki University Faculty of Medicine

AIM: To assess the usefulness of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for lymph node metastasis in pancreatobiliary ***: All patients suspected of pancreatobiliary carcinoma with visible lymph nodes after standard EUS between June, 2009 and January, 2012 were enrolled. In the primary analysis, patients with successful EUS-fine needle aspiration (FNA) were included. The lymph nodes were assessed by several standard EUS variables (short and long axis lengths, shape, edge characteristic and echogenicity), color Doppler EUS variable [central intranodal blood vessel (CIV) presence] and CH-EUS variable (heterogeneous/homogeneous enhancement patterns). The diagnostic accuracy relative to EUS-FNA was calculated. In the second analysis, N-stage diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent surgical ***: One hundred and nine patients (143 lymph nodes) fulfilled the criteria. The short axis cut-off ≥ 13 mm predicted malignancy with a sensitivity and specificity of 72% and 85%, respectively. These values were 72% and 63% for the long axis cut-off ≥ 20 mm, 62% and 75% for the round shape variable, 81% and 30% for the sharp edge variable, 66% and 61% for the hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and 91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was more accurate than standard and color Doppler EUS, except the short axis cut-off. Notably, three patients excluded because of EUS-FNA failure were correctly N-staged by ***: CH-EUS complements standard and color Doppler EUS and EUS-FNA for assessment of lymph node metastases.

关键词： Contrast-enhanced harmonic endoscopic ultrasonography Sensitivity and specificity Lymph node Pancreatobiliary carcinoma Endoscopic ultrasonography-fine needle aspiration

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Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

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World Journal of Gastroenterology 2011年第45期17卷 4952-4959页

作者： Yasunori Minami Masatoshi Kudo Department of Gastroen-terology and Hepatology Kinki University School of Medicine

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly def ined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in diffi cult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an effi cient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

关键词： Dynamic contrast-enhanced ultrasound Hepatocellular carcinoma Percutaneous ethanol injection Radiofrequency ablation

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On a Class of univ.lent Functions

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Journal of Mathematical Research with Applications 1991年第2期 193-201页

作者： M.K.Aouf S.Owa Dept. Math. Faculty of Science univ. of Qatar P. C. Box 2713 Doha-Qatar kinki univ. Higashi-Osaka Osaka 577 Japan

A sharp coefficient estimate,distortion theorem and the radius of convexityare determined for the class R（α,β,A,B）of function f（z）=z+sum from n=2 to∞azsatisfyingthe condition|f’（z）-1/Bf’（z）-[B+（A-B）(1-... 详细信息

关键词： On a Class of univ.lent Functions

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Urgent endoscopic ultrasound-guided choledochoduodenostomy for acute obstructive suppurative cholangitis-induced sepsis

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World Journal of Gastroenterology 2016年第16期22卷 4264-4269页

作者： Kosuke Minaga Masayuki Kitano Hajime Imai Kentaro Yamao Ken Kamata Takeshi Miyata Shunsuke Omoto Kumpei Kadosaka Tomoe Yoshikawa Masatoshi Kudo Department of Gastroenterology and Hepatology Kinki University Faculty of Medicine

Acute obstructive suppurative cholangitis(AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography(ERCP) with stent placement is the current gold standard for biliary decompression, it can sometimes be difficult because of failed biliary cannulation. In this retrospective case series, we describe three cases of successful biliary drainage with recovery from septic shock after urgent endoscopic ultrasound-guided choledochoduodenostomy(EUS-CDS) was performed for AOSC due to biliary lithiasis. In all three cases, technical success in inserting the stents was achieved and the patients completely recovered from AOSC with sepsis in a few days after EUS-CDS. There were no procedure-related complications. When initial ERCP fails, EUS-CDS can be an effective life-saving endoscopic biliary decompression procedure that shortens the procedure time and prevents post-ERCP pancreatitis, particularly in patients with AOSC-induced sepsis.

关键词： Endoscopic ultrasound-guided biliary drainage Choledochoduodenostomy Acute obstructive suppurative cholangitis Sepsis Life-saving endoscopy

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Percutaneous endoscopic gastrostomy with Funada-style gastropexy greatly reduces the risk of peristomal infection

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Gastroenterology Report 2015年第1期3卷 69-74页

作者： Naoki Okumura Naoko Tsuji Nobuto Ozaki Nozomu Matsumoto Takehisa Takaba Masanori Kawasaki Takafumi Tomita Yasuko Umehara Satoko Taniike Masashi Kono Masatoshi Kudo Department of Gastroenterology Sakai HospitalKinki University Faculty of MedicineSakaiJapan Department of Gastroenterology and Hepatology Kinki University Faculty of MedicineOsaka-sayamaJapan

Background and aims:Peristomal wound infections are common complications of percutaneous endoscopic gastrostomy(PEG).The Funada-style gastropexy device has two parallel needles with a wire loop and suture thread,and was developed about 20 years ago in *** kit has allowed us to perform dual gastropexy very easily;PEG with gastropexy has become a very popular technique in *** present study aimed to compare the advantages and disadvantages of PEG with the gastropexy technique with the standard‘pull’***:We retrospectively reviewed 182 consecutive,non-randomized patients undergoing PEG in our hospital,and a comparative analysis was made between the gastropexy(87 patients)and non-gastropexy(95 patients)***:The rates of patients having erythema(11.6%vs.47.9%;P<0.001),exudates(2.3%vs.14.9%;P<0.01)and infection(0%vs.6.4%;P紏0.01)in the peristomal area were lower in the gastropexy than in the non-gastropexy *** rate of minor bleeding from the peristomal area was higher in the gastropexy than in the non-gastropexy group(12.8%vs.2.1%;P<0.01),but no patient required a blood *** procedure time was longer in the gastropexy group than in the non-gastropexy group(31 vs.24 min;P<0.001).The 30-day mortality rates were 4.7%and 5.3%respectively,and these deaths were not related to the gastrostomy ***:PEG with gastropexy markedly reduces peristomal *** minor bleeding and a longer procedure time were disadvantages,there were no severe *** findings suggested that PEG with Funada-style gastropexy was a safe and feasible method for reducing early complications of PEG.

关键词： percutaneous endoscopic gastrostomy gastropexy peristomal infection

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Synthesis and adsorptivity of acryloylmorpholine resin to various fission product elements in nitric acid media

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Science China Chemistry 2014年第11期57卷 1459-1463页

作者： NISHIDA Tetsuhiro TANAKA Shotaro NOGAMI Masanobu Department of Electric and Electronic Engineering Faculty of Science and Engineering Kinki University

A novel silica-supported resin with a cyclic monoamide of polymerized 4-acryloylmorpholine(Silica-AM) was synthesized, and adsorptivity to metal ions of major fission products(FP) was examined in HNO3 and HCl solutions. Silica-AM has a carbonyl oxygen atom outside of the 6-membered morpholine ring, and a cyclic structure that is different than other cyclic monoamide resins we have studied. These include polyvinylpolypyrrolidone(PVPP) and poly-N-vinyl-ε-caprolactam(VEC), both of which have coordinative carbonyl groups included in the ring. Silica-AM was similar to a cyclic monoamide we have reported because it exhibited adsorption to Pd(Ⅱ) and Re(VⅡ) in HNO3 of a particularly low concentration range. Silica-AM has an ether oxygen atom included in the ring as well. Considering the difference in the chemical structures of Silica-AM and other cyclic monoamide resins, it was suggested that oxygen atoms in the carbonyl group and in ether may be main contributors to Silica-AM's respective adsorptions to Pd(Ⅱ) and Re(VⅡ), and Mo(VI) and Zr(IV). Our results imply that the contribution of the two types of oxygen atoms to adsorption is more observable in an HCl system. The contribution of the ether oxygen atom to the adsorption of Pd(Ⅱ) was also suggested from our study on crystal prepared from 4-acetylmorpholine and palladium nitrate.

关键词： monoamide resin acryloylmorpholine FP nitric acid

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Endoscopic findings can predict the efficacy of leukocytapheresis for steroid-naive patients with moderately active ulcerative colitis

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World Journal of Gastroenterology 2008年第34期14卷 5316-5321页

作者： Yasushi Umehara Masatoshi Kudo Masanori Kawasaki Division of Gastroenterology and Hepatology Department of Internal Medicine Kinki University School of Medicine

AIM:To investigate the therapeutic usefulness of leukocytapheresis (LCAP; Cellsoba) in steroid-naive patients with moderately active ulcerative colitis (UC). METHODS: Eighteen steroid-naive patients with moderately active UC received one LCAP session every week for fi ve consecutive weeks. RESULTS: The remission rate 8 weeks after the last LCAP session was 61.1% (11/18). All three patients with deep ulcers showed worsening after LCAP. For the remaining 15 patients, who had erosions or geographic ulcers, the average clinical activity index (CAI) score dropped significantly from 9.4 to 3.8 eight weeks after the last LCAP session (t = 4.89, P = 0.001). The average C-reactive protein (CRP) levels before and after LCAP were 1.2 mg/dL and 1.0 mg/dL, respectively. Of the patients with erosions, geographic ulcers, and deep ulcers, 100% (9/9), 33.3% (2/6), and 0% (0/3) were in remission 8 weeks after the last LCAP session, respectively (χ2 = 7.65, P < 0.005). Forty- eight weeks after the last LCAP session, the remission rates for patients with erosions and geographic ulcers were 44.4% (4/9) and 16.7% (1/6), respectively. Only one patient suffered a mild adverse event after LCAP (nausea). CONCLUSION: LCAP is a useful and safe therapyfor steroid-naive UC patients with moderate disease activity. Moreover, the effi cacy of the treatment can be predicted on the basis of endoscopic fi ndings.

关键词： Ulcerative colitis Steroid-naive Leukocytapheresis Efficacy Endoscopic findings

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