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International Journal of Organic Chemistry 2013年第4期3卷 243-250页

作者： Murugulla Adharvana Chari Zaied-A-Mosaa Donthabakthuni Shobha Sridhar Malayalama Dr. MACS Bio-pharma Pvt. Ltd. Pashamylaram Patancheru Hyderabad India Dr. MACS Bio-pharma Pvt. Ltd. Pashamylaram Patancheru Hyderabad India Center for Chemical Science & Technology Institute of Science & Technology Jawaharlal Nehru Technological University Hyderabad India College of Science for Women Babylon University Babylon Iraq

Here we demonstrate the synthesis of multifunctionalised benzimidazoles through the coupling of o-phenylenediamine with aldehydes by using Copper (II) hydroxide as an efficient solid catalyst in methanol at room temperature. The Copper (II) hydroxide solid catalyst gave better yields (80%-99%) in short reaction time (4-8 h). These commercially available cheap catalysts are more active than many reported expensive heterogeneous catalysts. Using the Copper hydroxide fresh catalyst, the yield of product 3a was 98%, while the recovered catalyst in the three subsequent cycles gave the yield of 94%, 90% and 88% respectively.

关键词： o-Phenylenediamine Aldehydes Copper (II) Hydroxide Solid Catalyst Multifunctionalised Benzimidazoles

Effect of chitin-architected spatiotemporal three-dimensional culture microenvironments on human umbilical cord-derived mesenchymal stem cells

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Bioactive Materials 2024年第5期35卷 291-305页

作者： Shuoji Zhu Junfeng Xuan Yunchao Shentu Katsuhiko Kida Masaki Kobayashi Wei Wang Minoru Ono Dehua Chang Department of Cardiac Surgery University of TokyoTokyo113-8655Japan Department of Cell Therapy in Regenerative Medicine University of Tokyo HospitalTokyo113-8655Japan Nissan Chemical Corporation Tokyo103-0027Japan Winhealth pharma 999077Hong Kong

Mesenchymal stem cell(MSC)transplantation has been explored for the clinical treatment of various ***,the current two-dimensional(2D)culture method lacks a natural spatial microenvironment in *** limitation restricts the stable establishment and adaptive maintenance of MSC *** natural polymers with biocompatibility for constructing stereoscopic MSC microenvironments may have significant application *** study used chitin-based nanoscaffolds to establish a novel MSC three-dimensional(3D)*** compared 2D and 3D cultured human umbilical cord-derived MSCs(UCMSCs),including dif-ferentiation assays,cell markers,proliferation,and *** UCMSCs are in 3D culture,they can differentiate into bone,cartilage,and *** 3D culture condition,cell proliferation is enhanced,accompanied by an elevation in the secretion of paracrine factors,including vascular endothelial growth factor(VEGF),hepa-tocyte growth factor(HGF),Interleukin-6(IL-6),and Interleukin-8(IL-8)by ***,a 3D culture environment promotes angiogenesis and duct formation with HUVECs(Human Umbilical Vein Endothelial Cells),showing greater luminal area,total length,and branching points of tubule formation than a 2D *** cultured in a 3D environment exhibit enhanced undifferentiated,as well as higher cell activity,making them a promising candidate for regenerative medicine and therapeutic applications.

关键词： Cellhesion®chitin nanoscaffolds Mesenchymal stem cells Stemness 3D culture

Probiotic Effect of Lebanese Darfiyeh Cheese: A Randomized Case Control Prospective Study in the Elderly

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Food and Nutrition Sciences 2015年第12期6卷 1086-1094页

作者： Toufic Saber Jihad Irani Claude Afif Nazem Bassil Elie Estephan Mireille Serhan Marcel Bassil Faculty of Health Sciences University of Balamand Beirut Lebanon Faculty of Medicine University of Balamand Beirut Lebanon Saint George Hospital-University Medical center Beirut Lebanon Biotechnology Department Benta Pharma Industries Dbayeh Lebanon

A randomized case control prospective method was adopted in this study in order to assess the health benefit associated with the Darfiyeh cheese, a traditional Lebanese raw goat milk cheese ripened in goat skin. 21 participants were recruited and divided into 2 groups: test group (n = 10) and control group (n = 11). Venous blood and stools were collected at day 14, 21 and day 0 and 21 respectively. Flow cytometry was performed on blood sample. Fecal samples were plated on Plate Count Agar (PCA) and de Man, Rogosa and Sharpe Agar (MRS) agar in order to monitor any alteration in the gastrointestinal tract (GIT). At day 24, a significant increase by 27.67% (p = 0.043) in the bacterial count was seen on the MRS agar for the test group in comparison to no change in the total bacterial count. At day 14 a significant drop (p = 0.026) in CD3+/CD4+ population in the test group (35.67 vs 42.87), and a non-significant drop (p = 0.818) in CD8+ (24.76 vs 28.28) is seen when compared to control group. At day 24, no significant change (p = 0.20) in the CD3+/CD4+ population in comparison between both groups and no change in CD8+ or Geo means in both groups. In conclusion, an alteration in the GIT microflora could be hinted at by the lactobacilli bacterium, which was not reflected on the total bacterial count.

关键词： Lactococcus lactis Subsp. Lacti Lactobacillus plantarum Darfiyeh Cheese Probiotic Effect Elderly

New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

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Bone Research 2014年第4期2卷 252-258页

作者： Sakae Tanaka Taiji Adachi Tatsuhiko Kuroda Toshitaka Nakamura Masataka Shiraki Toshitsugu Sugimoto Yasuhiro Takeuchi Mitsuru Saito John P Bilezikian Department of Orthopaedic Surgery Faculty of MedicineUniversity of TokyoTokyoJapan Department of Biomechanics Institute for Frontier Medical SciencesKyoto UniversityKyotoJapan Medical Affairs Department Asahi Kasei Pharma CorporationTokyoJapan National center for Global Health and Medicine TokyoJapan Research Institute and Practice for Involutional Diseases NaganoJapan Internal Medicine 1 Shimane University Faculty of MedicineIzumoJapan Toranomon Hospital Endocrine center TokyoJapan Department of Orthopaedic Surgery Jikei University School of MedicineTokyoJapan Metabolic Bone Diseases Program Division of EndocrinologyDepartment of MedicineCollege of Physicians and SurgeonsColumbia UniversityNew YorkUSA

Daily 20-mg and once-weekly 56.5-mg teriparatide（parathyroid hormone 1–34） treatment regimens increase bone mineral density（BMD） and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

关键词： bone New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide BMD

New categorization of human vascular endothelial cells by pro-vs anti-proliferative phenotypes

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World Journal of Translational Medicine 2015年第3期4卷 88-100页

作者： Miwako Nishio Masako Nakahara Chikako Sato Koichi Saeki Hidenori Akutsu Akihiro Umezawa Kazuyuki Tobe Kazuki Yasuda Akira Yuo Kumiko Saeki Department of Disease Control Research Institute National Center for Global Health and Medicine Section of Cell Engineering Department of Basic Research DNAVEC Center ID Pharma Co. Ltd. PRESTO Japan Science and Technology Agency Department of Reproductive Biology National Research Institute for Child Health and Development First Department of Internal Medicine School of Medicine Toyama University Department of Metabolic Disorder Diabetes Research Center Research Institute National Center for Global Health and Medicine

aiM: To integrally understand the effects of human vascular endothelial cells(VECs) on the proliferation of vascular smooth muscle cells(VSMCs).METHODS: Various kinds of human VECs of different origins were co-cultured with human aortic smooth muscle cells, a representative of human VSMCs. To exclude the irrelevant effects due to growth competition between VECs and VSMCs, the proliferation of VECs had previously been arrested via a low-dose gamma rayirradiation. To discriminately analyze the proliferation of VSMCs from that of VECs, the former cells were labeled with red fluorescent dye while the latter cells were labeled with green fluorescent dye before performing coculture experiments. After 4 d, total cells were harvested and subjected to flow cytometric analyses. Decrements in red fluorescence intensities due to proliferationmediated dilutions were measured and mathematically processed using a specific software to quantitatively evaluate the proliferation of VSMCs. The findings obtained from the flow cytometry-based analyses were further validated by microscopic observations. RESULTS: Commercially available primary cultured human VECs exclusively promoted VSMC proliferation regardless of their tissue origins and we termed these pro-proliferative VECs as "typeⅠ". By contrast, VECs freshly generated from human bone marrow-derived endothelial progenitors cells or human pluripotent stem cells including embryonic stem cells and induced pluripotent stem cells suppressed VSMC proliferation and we termed these anti-proliferative VECs as "typeⅡ". Repetitive subcultures as well as oxidative stress induced "type Ⅱ VECs to typeⅠ" conversion along with an induction of Regulator of G-protein signaling 5(RGS5)Compatibly, anti-oxidant treatments suppressed both the subculture-dependent "typeⅡ to typeⅠ" conversion and an induction of RGS5 gene. Immunostaining studies of clinical specimens indicated that RGS5 protein expressions in endothelial layers were low in norma arteries b

关键词： Vascular endothelial cells Vascular smooth muscle cells Human induced pluripotent stem cells Human embryonic stem cells Regulator of G-protein signaling 5 Oxidative stress

Deciphering active biocompatibility of iron oxide nanoparticles from their intrinsic antagonism

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Nano Research 2018年第5期11卷 2746-2755页

作者： Lu Wang Zejun Wang Xiaoming Li Yi Zhang Min Yin Jiang Li Haiyun Song Jiye Shi Daishun Ling Lihua Wang Nan Chen Chunhai Fan Division of Physical Biology and Bioimaging center Shanghai Synchrotron Radiation Focility CAS Key Laboratory of Interracial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China School of Life Scienceand Technology Shanghai Tech University Shanghai 201210 China Key Laboratory of Food Safety Research Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China UCB pharma 208 Bath Road Slough SL1 3WE UK College of pharmaceutical Sciences Zhejiang University Hangzhou 310058 China

Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.

关键词： catalase-like activity iron oxide nanoparticles autophagy cytotoxicity reactive oxygen species

Biological insights in non-small cell lung cancer

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Cancer Biology & Medicine 2023年第7期20卷 500-518页

作者： Rafael Rosell Anisha Jain Jordi Codony-Servat Eloisa Jantus-Lewintre Blake Morrison Jordi Barretina Ginesta María González-Cao Germans Trias i Pujol Research Institute Badalona 08028Spain IOR Hospital Quiron-DexeusBarcelona 08028Spain Department of Microbiology JSS Academy of Higher Education&ResearchMysuru 570015India Pangaea Oncology Hospital Quiron-DexeusBarcelona 08028Spain Department of Biotechnology Universitat Politècnica de ValenciaMixed Unit TRIAL(General University Hospital of Valencia Research Foundation and Príncipe Felipe Research Center)CIBERONCValencia 46014Spain Sumitomo pharma Oncology Inc.CambridgeMA and LehiUT 84043USA

Lung oncogenesis relies on intracellular cysteine to overcome oxidative *** tumor types,including non-small cell lung cancer(NSCLC),upregulate the system x-c cystine/glutamate antiporter(xCT)through overexpression of the cystine transporter SLC7A11,thus sustaining intracellular cysteine levels to support glutathione *** factor erythroid 2-related factor 2(NRF2)serves as a master regulator of oxidative stress resistance by regulating SLC7A11,whereas Kelch-like ECH-associated protein(KEAP1)acts as a cytoplasmic repressor of the oxidative responsive transcription factor *** in KEAP1/NRF2 and p53 induce SLC7A11 activation in *** cystine is crucial in supplying the intracellular cysteine levels necessary to combat oxidative *** in cystine availability lead to iron-dependent lipid peroxidation,thus resulting in a type of cell death called *** inhibitors of xCT(either SLC7A11 or GPX4)induce ferroptosis of NSCLC cells and other tumor *** cystine uptake is impaired,the intracellular cysteine pool can be sustained by the transsulfuration pathway,which is catalyzed by cystathionine-B-synthase(CBS)and cystathionine g-lyase(CSE).The involvement of exogenous cysteine/cystine and the transsulfuration pathway in the cysteine pool and downstream metabolites results in compromised CD8^(+)T cell function and evasion of immunotherapy,diminishing immune response and potentially reducing the effectiveness of immunotherapeutic *** is a previously unrecognized form of regulated cell *** NSCLCs driven by EGFR,ALK,or KRAS,selective inhibitors induce pyroptotic cell death as well as *** targeted therapy,the mitochondrial intrinsic apoptotic pathway is activated,thus leading to the cleavage and activation of ***,gasdermin E is activated,thus leading to permeabilization of the cytoplasmic membrane and cell-lytic pyroptosis(indicated by characte

关键词： Solute carrier family 7 member 11(SLC7A11) nuclear factor erythroid 2-related factor 2(NRF2) ferroptosis pyroptosis KRAS G12C allele-specific inhibitors non-small cell lung cancer(NSCLC)

Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients:An interim analysis of post-marketing surveillance

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World Journal of Psychiatry 2023年第11期13卷 937-948页

作者： Yu-Mei Wei Xi-Jin Wang Xiao-Dong Yang Chuan-Sheng Wang Li-Li Wang Xiao-Ying Xu Gui-Jun Zhao Bin Li Dao-Min Zhu Qi Wu Yi-Feng Shen Shanghai Clinical Research center for Mental Health School of MedicineShanghai Jiao Tong UniversityShanghai 200030China Department of Psychiatry The First Psychiatric Hospital of HarbinHarbin 150056Heilongjiang ProvinceChina Department of Psychiatry Shandong Provincial Mental Health CenterJinan 250014Shandong ProvinceChina Department of Psychiatry The Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453002Henan ProvinceChina Department of Psychiatry Tianjin Mental Health CenterTianjin Anding HospitalTianjin 300222China Department of Psychiatry The Fifth People’s Hospital of ZigongZigong 643020Sichuan ProvinceChina Department of Psychiatry Guangyuan Mental Health CenterGuangyuan 628001Guizhou ProvinceChina Department of Psychology Fujian Energy General HospitalFuzhou 350001Fujian ProvinceChina Department of Sleep Disorders Affiliated Psychological Hospital of Anhui Medical UniversityHefei Fourth People’s HospitalAnhui Mental Health CenterHefei 230022Anhui ProvinceChina Sumitomo pharma(China) Co.Ltd.Shanghai 200025China Shanghai Key Laboratory of Psychotic Disorders Shanghai Clinical Research Center for Mental HealthShanghai Jiao Tong UniversityShanghai 200030China

BACKGROUND Schizophrenia is a psychiatric disorder characterized by chronic or recurrent *** was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/***,post-market surveillance(PMS)with an adequate sample size is required for further validation of the drug’s safety profile and *** To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese *** A prospective,multicenter,open-label,12-wk surveillance was conducted in China's *** patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for *** assessments included adverse events(AEs),adverse drug reactions(ADRs),extrapyramidal symptoms(EPS),akathisia,use of EPS drugs,weight gain,and laboratory values as metabolic parameters and the QTc *** effectiveness was assessed using the brief psychiatric rating scale(BPRS)from baseline to the end of *** A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim *** average daily dose was 61.7±19.08 mg(mean±SD)during the *** and ADRs were experienced by 101 patients(11.3%)and 78 patients(8.7%),respectively,which were mostly *** occurred in 25 individuals with a 2.8%incidence,including akathisia in 20 individuals(2.2%).Moreover,59 patients received drugs for treating EPS during the treatment,with an incidence of 6.6%which dropped to 5.4%at the end of the *** average weight change was 0.20±2.36 kg(P=0.01687)with 0.8%of patients showing a weight gain of≥7%at week 12 compared with that at the *** mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal *** mean changes in total BPRS scores were-8.9±9.76(n=959),-13.5±12.29(n=959),and-16.8±13.97(n=959)after 2/4,6/8,a

关键词： Lurasidone Safety Effectiveness Surveillance Schizophrenia Chinese

组织工程材料表面物理化学性质对细胞相容性的影响(英文)

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中国组织工程研究与临床康复 2007年第1期11卷 197-200页

作者：陈宝林王东安封麟先呼伦贝尔学院科研处浙江大学高分子科学研究所 Department of pharma-ceutical Sciences University of Tennessee Health Science CenterMemphis Tennessee 38163

目的: 从材料表面能、材料表面的亲 / 疏水性、材料表面的电荷状况、材料表面的化学结构和材料表面负载活性因子 5 个方面论述了材料表面物理化学性质对细胞相容性的影响。指出材料表面的物理化学性质对材料的细胞相容性有着较大影响, ... 详细信息

目的: 从材料表面能、材料表面的亲 / 疏水性、材料表面的电荷状况、材料表面的化学结构和材料表面负载活性因子 5 个方面论述了材料表面物理化学性质对细胞相容性的影响。指出材料表面的物理化学性质对材料的细胞相容性有着较大影响, 暨从这个方面阐明了组织工程材料的细胞相容性问题。资料来源: 应用计算机检索 PUBMED 1997- 12/2006- 12 期间的相关文章 , 检索词为“bio-compatibility, bio-compatibility materials, tissueengineering, tissue engineering materials, cell-compatibility”, 并限定文章语言种类为 English。同时计算机检索万方数据库 1997- 12/2006-12 期间的相关文章, 检索词为“生物相容性, 生物相容性材料, 组织工程, 组织工程材料, 细胞相容性”, 并限定文章语言种类为中文。资料选择: 对资料进行初审, 纳入标准: 与生物相容性组织工程材料相关的文章。排除标准: 重复研究或 Meta 分析类文章。资料提炼: 共收集到 71 篇相关文献, 33 篇文献符合纳入标准, 排除的38 篇文献为内容陈旧或重复。符合纳入标准的 33 篇文献中, 22 篇涉及生物相容性, 11 篇涉及细胞相容性材料。资料综合: ①关于组织工程材料与生物体的相互作用: 综述了高分子组织工程材料在与生物体组织接触时发生各种各样的相互作用。指出了材料与生物体的相互作用情况决定了材料组织相容性的程度; 材料对组织相容性的影响包含着微观分子水平和宏观尺度水平, 而且, 宏观大尺度上的效应比分子尺度上发生的化学效应更为重要。②关于材料表面物理化学性质对材料细胞相容性的影响: 综述了高分子材料表面的化学性质和结构、表面组成、表面能、表面亲 / 疏水性、表面的电荷状况、表面负载活性因子等材料表面物理化学性质对材料细胞相容性的影响。指出这种影响是研究组织工程材料生物相容性的重要内容及进行组织相容性材料设计的重要内容。结论: 材料表面的物理化学性质对材料的细胞相容性有着较大影响, 细胞与聚合物的相互作用是评价材料细胞相容性的指标。细胞与高分子材料间短期的相互作用程度可由细胞与高分子材料表面的黏附程度来评价, 而长期的相互作用可通过检测体外培养细胞的生长情况或在体内植入高分子材料进行长期评估。

关键词：生物相容性生物相容性材料组织工程组织工程材料细胞相容性综述文献