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Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver

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World Journal of Gastroenterology 2015年第11期21卷 3291-3299页

作者： Motoyuki Kohjima Tsuyoshi Yoshimoto Munechika Enjoji Nobuyoshi Fukushima Kunitaka Fukuizumi Tsukasa Nakamura Miho Kurokawa Nao Fujimori Yusuke Sasaki Yasushi Shimonaka Yusuke Murata Susumu Koyama Ken Kawabe Kazuhiro Haraguchi Yorinobu Sumida Naohiko Harada Masaki Kato Kazuhiro Kotoh Makoto Nakamuta Department of Gastroenterology and clinical research Center National Hospital Organization Kyushu Medical Center Health Care Center Fukuoka University Product research Department Chugai Pharmaceutical Co.Ltd. Department of Medicine and Bioregulatory Science Kyushu University

AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C ***:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively *** biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for *** a control,normal liver tissue was obtained from 18 living donors of liver *** hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass ***:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in ***,iron administration suppresses HCV replication in ***,the association between HCV infection and iron metabolism remains *** with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and *** the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and *** of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected ***2 and hemojuvelin expression was significantly lower in the SVR than non-SVR *** infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in ***:Decrea

关键词： Chronic hepatitis C Iron-metabolism Hepcidin Ferro

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Diabetic cardiomyopathy:Importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis

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World Journal of Diabetes 2024年第8期15卷 1659-1662页

作者： Lu Cai Yi Tan Md Shahidul Islam Michael Horowitz Kupper A Wintergerst Pediatric research Institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Department of Medicine University of AdelaideAdelaide 5005Australia Pediatric research Institute Division of EndocrinologyDepartment of PediatricsWendy Novak Diabetes InstituteNorton Children’s HospitalUniversity of LouisvilleLouisvilleKY 40202United States

Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively ***,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and *** direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific *** thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific *** editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent *** clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.

关键词： Diabetic cardiomyopathy Nucleotide oligomerization domain NOD-like receptor protein 3 inflammasome Cardiac cell death Pyroptosis

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Targeted trace ingredients coupled with chemometric analysis for consistency evaluation of Panax notoginseng saponins injectable formulations

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中国天然药物:英文版 2023年第8期21卷 631-640页

作者： ZHANG Jingxian ZHANG Zijia WANG Zhaojun ZHANG Tengqian ZHOU Yang CHEN Ming HUANG Zhanwen HE Qingqing LONG Huali HOU Jinjun WU Wanying GUO Dean National Engineering research Center of TCM Standardization Technology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine Shanghai Institute for Food and Drug ControlShanghai 201203China Guangxi Key Laboratory of Comprehensive Utilization Technology of Pseudo-Ginseng Guangxi Zhongheng Innovative Pharmaceutical Research Co.Ltd.Guangxi 530032China School of Pharmacy University of Chinese Academy of SciencesBeijing 100049China

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety,particularly concerning the composition and content levels of trace *** notoginseng Saponins Injection(PNSI),widely used in China for treating acute cardiovascular diseases,contains low-abundance(10%-25%)and trace saponins in addition to its five main constituents(notoginsenoside R1,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,and ginsenoside Rd).This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation *** achieve this,a liquid chromatography-triple quadrupole mass spectrometry(LC-MS/MS)method employing multiple ions monitoring(MIM)was developed.A“post-column valve switching”strategy was implemented to eliminate highly abundant peaks(NR_(1),Rg_(1),and Re)at 26 min.A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards,with digoxin as the internal *** study evaluated 119 batches of PNSI from seven vendors,revealing significant variability in trace saponin levels among different vendors and formulation *** findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical *** of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.

关键词： Consistency evaluation Panax notoginseng saponins PCA analysis Xueshuantong Xuesaitong

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Determination of risperidone in human plasma by HPLC-MS/MS and its application to a pharmacokinetic study in Chinese volunteers

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第2期9卷 114-120页

作者： Ming-zhu HUANG Jian-zhong SHENTU Jun-chun CHEN Jian LIU Hui-li ZHOU research Center of clinical pharmaceutical Science the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China

This study presents a rapid, specific and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of risperidone (RIS) in human serum using paroxetine as an internal standard (IS). An Alltima-C18 column (2.1 mm×100 mm, 3 μm) and a mobile phase consisting of 0.1% formic acid-acetonitrile (40:60, v/v) were used for separation. The analysis was performed by selected reaction monitoring (SRM) method, and the peak area of the m/z 411.3→191.1 transition for RIS was measured versus that of the m/z 330.1→192.1 transition for IS to generate the standard curves. The assay linearity of RIS was confirmed over the range 0.25～50.00 ng/ml and the limit of quantitation was 0.05 ng/ml. The linear range corresponds well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations were 1.85%～9.09% and 1.56%～4.38%, respectively. The recovery of RIS from serum was in the range of 70.20%～84.50%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference products) in 18 healthy male Chinese volunteers. The result suggests that two formulations are bioequivalent.

关键词：高性能液体液态色谱法 HPLC-MS/MS 药动学

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Bioreactor design and validation for manufacturing strategies in tissue engineering

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Bio-Design and Manufacturing 2022年第1期5卷 43-63页

作者： Diana Lim Eric S.Renteria Drake S.Sime Young Min Ju Ji Hyun Kim Tracy Criswell Thomas D.Shupe Anthony Atala Frank C.Marini Metin N.Gurcan Shay Soker Joshua Hunsberger James J.Yoo Wake Forest Institute for Regenerative Medicine Wake Forest School of MedicineWinston-SalemNC 27157USA Center for Biomedical Informatics Wake Forest School of MedicineWinston-SalemNC 27157USA RegenMed Development organization(ReMDO) Winston SalemNC 27106USA

The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or *** maximize the biological function of a tissue-engineered clinical product,specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for ***,the bioreactor should be designed to mimic the mechanical,electrochemical and biochemical environment that the product will be exposed to in ***-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management *** present review provides a brief overview of bioreactor engineering *** addition,strategies for bioreactor automation,in-line product monitoring and quality assurance are discussed.

关键词： Bioreactor Monitoring sensors and automation Manufacturing Tissue engineering Regenerative medicine

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A review of the efficacy of traditional Iranian medicine forinflammatory bowel disease

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World Journal of Gastroenterology 2010年第36期16卷 4504-4514页

作者： Roja Rahimi Mohammad Abdollahi Mohammad Reza Shams-Ardekani Faculty of Traditional Medicine Tehran University of Medical SciencesTehran ***Iran Faculty of Pharmacy Pharmaceutical Sciences Research CenterEndocrinology and Metabolism Research InstituteTehran University of Medical SciencesTehran ***Iran

The etiology of inflammatory bowel disease(IBD) is not yet known,but many factors such as defects in the immune system,oxidative stress,microbial content in the gastrointestinal tract,nuclear factor(NF)-κB,nitric oxide(NO),cyclooxygenase-2(Cox-2),and leukotriene B4(LB4) are thought to play a role in its *** traditional Iranian medicine(TIM),several medicinal plants are thought to be effective for the treatment of *** this study,information on all of these remedies were derived from all available old sources such as documents or notes and books and were added to the information derived from modern medical databases covering all in vitro,in vivo and clinical *** some of these plants,only one or two mechanisms of action have been found such as in Cassia fistula,Lepidium sativum,and Bunium ***,for some plants various mechanisms of action are *** example,Commiphora mukul is effective in IBD due to its immunomodulatory,antioxidant,and antibacterial properties and it decreases NF-κB,NO and *** herb,Plantago ovata,has immunomodulatory,antioxidant,anti-inflammatory and wound healing activities and decreases NO and *** the mechanisms of action of these plants,the combination of some of them may be useful because of their many mechanisms of action such as Pistacia lentiscus,Bunium persicum,Solanum nigrum,Plantago ovata,Boswellia,Solanum nigrum,Plantago ovata and Commiphora *** some of the herbal products used in TIM such as oleogum resin from Commiphora myrrha,seeds of Ocimum basilicum,seeds of Linum usitatissimum,gum resin of Dracaena cinnabari,seeds of Plantago major,seeds of Lallementia royleana,and seeds of Allium porrum,there is no or not enough studies to confirm their benefits in *** is suggested that an evaluation of the effects of these plants on different aspects of IBD should be performed.

关键词： Herbal medicine Inflammatory bowel disease Medicinal plants Traditional Iranian medicine

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Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2013年第3期4卷 54-60页

作者： Tatsuya Fujino Yoko Aoyagi Mariko Takahashi Ryoko Yada Naoko Yamamoto Yuki Ohishi Akihiko Nishiura Motoyuki Kohjima Tsuyoshi Yoshimoto Kunitaka Fukuizumi Manabu Nakashima Masaki Kato Kazuhiro Kotoh Makoto Nakamuta Munechika Enjoji Laboratory for clinical Investigation National Hospital Organization Nagasaki Medical CenterOhmuraNagasaki 856-8562Japan clinical research Institute National Hospital Organization Kyushu Medical CenterFukuoka 814-0180Japan Faculty of pharmaceutical Sciences Fukuoka UniversityFukuoka 814-0180Japan Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityFukuoka 814-0180Japan

AIM:To analyzed the association between inosine triphosphatase(ITPA)(rs1127354) genotypes and sustained virological response(SVR) rates in peginterferon(Peg-IFN)α + ribavirin(RBV) ***:Patients who underwent Peg-IFNα + RBV combination therapy were enrolled(n = 120) and they had no history of other IFN-based *** in hemoglobin levels during therapy,cumulative reduction of RBV dose,frequency of treatment withdrawal,and SVR rates were investigated in each ITPA ***:In patients with ITPA CC genotype,hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA ***,SVR rates were equivalent between CC and CA/AA genotypes,and within a subset of patients with Interleukin 28B(IL28B)(rs8099917) TT genotype,SVR rates tended to be higher in patients with ITPA CC genotype,although the difference was not ***:ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV ***,CC genotype was not inferior to CA/AA genotype for SVR *** full-length treatment is accomplished,it is plausible that more SVR is achieved in patients with ITPA CC variant,especially in a background of IL28B TT genotype.

关键词： Chronic hepatitis C Interleukin 28B Inosine triphosphatase Peginterferon Ribavirin

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The Synthesis and Cytotoxicity of Novel Thiophene Derivatives Derived from 2-(4-Oxo-4,4-Dihydrothiazol-2-yl) Acetonitrile

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International Journal of Organic Chemistry 2016年第2期6卷 85-94页

作者： Eman M. Samir Amr S. Abouzied Faten I. Hamed National organization for Drug Control & research (NODCAR) Cairo Egypt Department of pharmaceutical Chemistry College of Pharmacy University of Hail Hail Kingdom of Saudi Arabia

The reaction of the 2-(4-oxo-4,4-dihydrothiazol-2-yl)acetonitrile 1 with cyaclopentanone (2) afforded the condensed product 3. The latter underwent a series of heterocyclizations through its reaction with different reagents. Moreover, compound 1 underwent the Gewald’s thiophene to afford compounds 15 and 17. The reaction of either hydrazine hydrate or phenylhydrazine with compound 17 gave the hydrazide derivatives 19a and 19b, respectively. The cytotoxicity of the newly synthesized products was measured towards the three cancer cell lines MCF-7, NCI-H460 and SF-268. The study showed that compounds 3, 5, 9c, 11, 13a, 13c, 17 and 19b were the most active compounds towards the three cancer cell lines.

关键词： Thiazole Cyclopentanone Thiophene Hydrazide Cytotoxicity

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Allele-aware chromosome-level genome assembly of Artemisia annua reveals the correlation between ADS expansion and artemisinin yield

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Molecular Plant 2022年第8期15卷 1310-1328页

作者： Baosheng Liao Xiaofeng Shen Li Xiang Shuai Guo Shiyu Chen Ying Meng Yu Liang Dandan Ding Junqi Bai Dong Zhang Tomasz Czechowski Yi Li Hui Yao Tingyu Mai Caroline Howard Chao Sun Haitao Liu Jiushi Liu Jin Pei Jihai Gao Jigang Wang Xiaohui Qiu Zhihai Huang Hongyi Li Ling Yuan Jianhe Wei lan Graham Jiang Xu Boli Zhang Shilin Chen Instituteof ChineseMateria Medica China Academyof ChineseMedical SciencesBeijing 100700China Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong Provincial Medical products Administration the Second Clinical CollegeGuangzhou Universityof ChineseMedicineGuangzhou510006China Institute of Medicinal Plant Development Chinese Academy of Medical SciencesBeijing 100193China Artemisinin research.Center China Academy of Chinese Medical SciencesBeijing 100700China Pharmacy College Chengdu University of Traditional Chinese MedicineChengdu 611137China Centre for Novel Agricultural products Department of BiologyUniversity of YorkYorkUK Wellcome Sanger Institute Wellcome Trust Genome CampusHinxton CB101RQUK Kentucky Tobacco research and Development Center University of KentuckyLexingtonKY 40546USA Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement&Guangdong Provincial Key Laboratory of Applied Botany South China Botanical GardenChineseAcademyof SciencesGuangzhou 510520China School of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 300193China Chengdu University of Traditional Chinese Medicine Chengdu 611137China

Artemisia annua is the major natural source of artemisinin,an anti-malarial medicine commonly used ***,we present chromosome-level haploid maps for two *** strains with different artemisinin contents to explore the relationships between genomic organization and artemisinin ***-fidelity sequencing,optical mapping,and chromatin conformation capture sequencing were used to assemble the heterogeneous and repetitive genome and resolve the haplotypes of *** 5o,ooo genes were annotated for each haplotype genome,and a triplication event that occurred approximately 58.12million years ago was examined for the first time in this species.A total of 3,903,467-5,193,414 variants(SNPs,indels,and structural variants)were identified in the 1.5-Gb genome during pairwise comparison between haplotypes,consistent with the high heterozygosity of this *** analyses revealed a correlation between artemisinin concents and the copy number of amorpha-4,11-dienes *** correlation was further confirmed by resequencing of *** samples with varied artemisinin *** consensus sequencing of transcripts facilitated the detection of paralog ***,our study provides chromosome-level allele-aware genome assemblies for two *** strains and new insights into the biosynthesis of artemisinin and its regulation,which will contribute to conquering malaria worldwide.

关键词： Artemisia annua artemisinin haplotype chromosome amorpha-4 11-diene synthase copy number variation

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Sprinkle formulations——A review of commercially available products

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Asian Journal of pharmaceutical Sciences 2020年第3期15卷 292-310页

作者： Han Sol Lee Jeong-Jun Lee Myeong-Gyu Kim Ki-Taek Kim Cheong-Weon Cho Dae-Duk Kim Jae-Young Lee College of Pharmacy Chungnam National UniversityDaejeon 34134Republic of Korea Graduate School of clinical Pharmacy CHA UniversityPocheon 11160Republic of Korea College of Pharmacy and Natural Medicine research Institute Mokpo National UniversityJeonnam 58554Republic of Korea College of Pharmacy and research Institute of pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea

Currently, sixty-five original sprinkle drug products are available in various dosage forms including tablets, powders, granules, immediate-release capsules, extended-release capsules, delayed-release capsules, and multiparticulate drug delivery systems. By sprinkling on soft food vehicles, these products provide dosing flexibility and convenience of administration, which potentially improve the compliance of patients with *** to these advantages, the growth of sprinkle products picked up since the 1990s, and several regulatory issues regarding this dosage form have been raised and *** this article, the types of sprinkle formulations were discussed by dividing them into seven categories, and the commercial products were summarized in terms of the drug substance, pharmaceutical excipients, storage conditions and administration methods. In addition, several US Food and Drug Administration guidelines related to the regulatory issues of sprinkle formulations were reviewed, which led to the conclusion that the future development of this promising dosage form demands integrated guidance for industry rather than scattered information in various documents.

关键词： Sprinkle formulation Soft food Geriatric Pediatric Dysphagia Guidance for industry

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