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MCC1019,a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel,potent anticancer candidate

Acta Pharmaceutica Sinica b 2019年第5期9卷 1021-1034页

作者： sara Abdelfatah Angela berg Qi Huang Li Jun Yang Sami Hamdoun Anette Klinger Henry J.Greten Edmond Fleischer Thorsten berg Vincent K.W.Wong Thomas Efferth Department of Pharmaceutical biology Institute of Pharmacy and BiochemistryJohannes Gutenberg UniversityMainz55128Germany Leipzig University Institute of Organic ChemistryLeipzig04103Germany State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacaoChina MicroCombiChem GmbH Wiesbaden65203Germany Abel Salazar Institute of biomedical Sciences University of PortoPorto4099-003Portugal

Polo-like kinase(PLK1) has been identified as a potential target for cancer *** a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain(PbD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethylbenzofuran-2-carboxylic acid ethyl ester(designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PbD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PbD. The activity of compound MC1019 against the PLK1 PbD was confirmed using fluorescence polarization and microscale *** compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest—a phenomenon known as mitotic catastrophe, which is followed by immediate cell death via apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in vivo in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.

关键词： Polo-like kinase PLK1 Polo box domain Mono-targeted therapy Cell cycle Necroptosis Spindle damage

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The aflatoxin b1 isolating potential of two lactic acid bacteria

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Asian Pacific Journal of Tropical biomedicine 2013年第9期3卷 732-736页

作者： Adel Hamidi Reza Mirnejad Emad Yahaghi Vahid behnod Ali Mirhosseini Sajad Amani sara Sattari Ebrahim Khodaverdi Darian Department of Microbiology Razi Vaccine and Serum Research Institute Molecular biology Research Center Baqiyatallah University of Medical Sciences Young Researchers and Elite Club Damghan BranchIslamic Azad University Department of Microbiology Dameghan BranchIslamic Azad University Applied microbiology research center baqiyatallah university of medical sciences Young Researchers and Elite Club Tonkabon BranchIslamic Azad University Department of Microbiology Science and research BranchIslamic Azad University Young Researchers and Elite Club Karaj BranchIslamic Azad University

Objective:To determine lactic acid bacteria's capability to enhance the process of binding and isolating aflatoxin b1 and to utilize such lactic acid bacteria as a food supplement or probiotic products for preventing absorption of aflatoxin bl in human and animal ***:In the present research,the bacteria were isolated from five different *** surveying the capability of the bacteria in isolating aflatoxin bl,ELISA method was implemented,and for identifying the resultant strains through 16S rRNA sequencing method,universal primers were ***:Among the strains which were isolated,two strains of Lactobacillus pentosus and Lactobacillus beveris exhibited the capability of absorbing and isolating aflatoxin bl by respectively absorbing and discharging 17.4%and 34.7%of the aforementioned toxin existing in the experiment ***:Strains of Lactobacillus pentosus and Lactobacillus beveris were isolated from human feces and local milk samples,*** both strains has the ability to isolate or bind with aflatoxin bl.

关键词： Mycotoxin Aflatoxin Lactic acid bacteria ELISA test

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Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with crohn's disease

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World Journal of Gastroenterology 2015年第14期21卷 4379-4384页

作者： Andrea Taddio Alberto Tommasini Erica Valencic Ettore biagi Giuliana Decorti sara De Iudicibus Eva Cuzzoni Giuseppe Gaipa Raffaela badolato Alberto Prandini Andrea biondi Alessandro Ventura Institute for Maternal and Child Health-IRCCS "burlo Garofolo" -Trieste and University of Trieste Institute for Maternal and Child Health-IRCCS "burlo Garofolo"-Trieste "Matilde Tettamanti" Research Centre Laboratory of Cell Therapy "Stefano Verri"Paediatric ClinicUniversity of Milano-BicoccaSan Gerardo Hospital Department of Life Sciences University of Trieste Clinical Department of Medical Surgical and Health SciencesUniversity of Trieste Department of Clinical and Experimental Sciences Institute of Molecular Medicine "Angelo Nocivelli"University of Brescia

Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in *** has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune *** present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory b-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear *** these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell *** results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.

关键词： Autoimmune disease Crohn’s disease Interferon-γ pr

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bull spermatozoa selected by thermotaxis exhibit high DNA integrity,specific head morphometry,and improve ICSI outcome

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Journal of Animal Science and biotechnology 2023年第3期14卷 1001-1011页

作者： sara Ruiz-Diaz Rosane Mazzarella Paula Navarrete-Lopez Raul Fernandez-Gonzalez Celia de Frutos Maria Maroto Claudia Cucala Paula beltran-brena Marta Lombo Dimitrios Rizos Alfonso Gutierrez-Adan Department of Animal Reproduction INIA-CSIC28040 MadridSpain Mistral Fertility Clinics S.L Clinica TambreCalle Tambre828002 MadridSpain

background Sperm migration by thermotaxis is a guidance mechanism that operates along the oviduct and it has proved to be a valid method for selecting spermatozoa with low DNA fragmentation(SDF)in mice,humans,and *** study aimed to analyse if bull spermatozoa could be selected by thermotaxis and to assess their quality in terms of SDF as well as determine the presence of a specific sperm subpopulation based on sperm morphometry and assess their fertilizing capacity by *** We used frozen-thawed sperm from 6 bulls and sperm selection by thermotaxis was performed with TALP medium supplemented with 25 mmol/L of HEPES and 5 mmol/L of *** these conditions,sperm selection was achieved,obtaining a net thermotaxis of 3.6%.Subsequently,we analysed the SDF of the migrated and not-migrated spermatozoa using the neutral COMET assay,and we evaluated the size of the sperm head using Hemacolor■ staining with Motic Images Plus 3 ***,migrated and not-migrated spermatozoa by thermotaxis were used to fertilize bovine in vitro matured(IVM)oocytes by ICSI,a very inefficient procedure in cattle that is only successful when the oocyte is artificially *** The results showed lower SDF(χ^(2),Pbution of sperm subpopulations structure varied between groups,highlighting cluster 2,characterized by spermatozoa with small head size,and high ellipticity and elongated heads,as the most abundant in the thermotaxis migrated *** performed ICSI(without oocyte artificial activation)with the thermotactic sperm,the blastocyst rate was 32.2%±9.3%in the group microinjected with the thermotactic spermatozoa vs.8.3%±7.8%in the group of not-migrated sperm(χ^(2),Pbull sperm selection by thermotaxis has a much higher D

关键词： ART bovine Sperm morphometry Sperm selection Thermotaxis

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CRISPR/Cas9 editing of the polygalacturonase FaPG1 gene improves strawberry fruit firmness

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Horticulture Research 2023年第3期10卷 201-210页

作者： Gloria López-Casado Cristina Sánchez-Raya Pablo D.Ric-Varas Candelas Paniagua Rosario blanco-Portales Juan Muñoz-blanco sara Pose Antonio J.Matas Jose A.Mercado Departamento de botánica y Fisiología Vegetal Instituto de Hortofruticultura Subtropical y Mediterránea‘La Mayora’(IHSM-UMA-CSIC)Universidad de Málaga29071 MálagaSpain Departamento de bioquímica y biología Molecular Universidad de Córdoba14071CórdobaSpain

Firmness is one of the most important fruit quality traits in *** postharvest shelf life of this soft fruit is highly limited by the loss of firmness,where cell wall disassembly plays an important *** studies demonstrated that the polygalacturonase FaPG1 has a key role in remodelling pectins during strawberry *** this study,FaPG1 knockout strawberry plants have been generated using the CRISPR/Cas9 system delivered via Agrobacterium *** independent lines,cv.“Chandler”,were obtained,and all of them were successfully edited as determined by PCR amplification and T7 endonuclease *** targeted mutagenesis insertion and deletion rates were analyzed using targeted deep *** percentage of edited sequences varied from 47%up to almost 100%,being higher than 95%for seven of the selected *** analyses showed that 7 out of the eight lines analyzed produced fruits significantly firmer than the control,ranging from 33 to 70%increase in *** was a positive relationship between the degree of FaPG1 editing and the rise in fruit *** changes were observed in other fruit quality traits,such as colour,soluble solids,titratable acidity or anthocyanin *** fruits showed a reduced softening rate during postharvest,displayed a reduced transpirational water loss,and were less damaged by botrytis cinerea *** analysis of four potential off-target sites revealed no mutation *** conclusion,editing the FaPG1 gene using the CRISPR/Cas9 system is an efficient method for improving strawberry fruit firmness and shelf life.

关键词： fir straw PG1

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Hemophagocytic lymphohistiocytosis caused by primary Epstein-barr virus in patient with Crohn's disease

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World Journal of Gastrointestinal Surgery 2013年第11期5卷 306-308页

作者： Francesco Virdis sara Tacci Federico Messina Massimo Varcada Department of Emergency General Surgery Royal Free HospitalLondonGreater London NW3 2QGUnited Kingdom

We present a case of a 19-year-old man with a 6-year history of Crohn's disease(CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-barr virus(EbV) infection and subsequently developed a hemophagocytic lymphohistiocytosis(HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EbV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease(IbD) treated with thiopurines. Specific EbV-related clinical and virological management should be considered when treating a patient with IbD with immunosuppressive therapy. Moreover EbV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large b cell lymphoma. Our case confirms what is described in the literature; patients with IbD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.

关键词： Crohn’s disease Hemophagocytic lymphohistiocytosis Epstein-barr virus infection Immunosupressive therapy Thiopurines

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Effect of Different Calcination Process and Gd<sub>2</sub>O<sub>3</sub>as Impurities on the Different Phases of bi-based Superconductor

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World Journal of Condensed Matter Physics 2012年第3期2卷 148-152页

作者： Ahmad Amirabadizadeh sara Memarzadeh Naser Tajabor Hadi Arabi Department of Physics Faculty of Science Fer-dowsi University of Mashhad Mashhad Iran Department of Physics Faculty of Science University of Birjand Birjand Iran

In this research two samples of a nominal composition bi1.6Pb0.4Sr2Ca2Cu3Ox were prepared by the solid state reaction method, using two different routes. Codes A and b are used to refer to the two samples. In preparing sample A, the standard method for calcination was used, while for sample b, the SrCO3 and CaCO3 were calcinated at 1100℃ for 3 h. Calcination was done separately on SrCO3 and CaCO3 in order to eliminate CO2. Then after mixing and grinding, the powder mixtures of bi2O3, CuO, PbO, SrO and CaO were calcinated at 840℃ for 70 h. Also, the samples (samples C) of nominal compositions bi1.6Pb0.4Sr2Ca2Cu3Ox+ % x Gd2O3 (% x = 0, 3, 5, 7 and 9) have been synthesized by this method. The XRD and SEM results show that addition of Gd2O3 helps to increase the amount of bi-2212 phase, while alternative calcination process improves the formation of the bi-2223 phase. In addition, the AC susceptibility measurements confirm the XRD and SEM results.

关键词： bi-Pb-Sr-Ca-Cu-O System X-Ray Diffraction Scanning Electron Microscopy AC Susceptibility

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Retrospective Cohort Study on Acute Care in Obstetrics and Gynecology: Analogies and Differences When Compared to Emergency Medicine

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Open Journal of Obstetrics and Gynecology 2017年第4期7卷 473-485页

作者： Giuseppe Chiossi Stefano Palomba sara balduzzi Maged M. Costantine Angela I. Falbo Anna M. Ferrari Giovanni b. La Sala Department of Obstetrics and Gynecology University of Texas Medical Branch Galveston TX USA Department of Obstetrics and Gynecology Arcispedale Santa Maria Nuova IRCCS Reggio Emilia Italy Statistics Unit Department of Oncology Hematology and Respiratory Diseases University of Modena and Reggio Emilia Modena Italy Department of Emergency Medicine Arcispedale Santa Maria Nuova IRCCS Reggio Emilia Italy University of Modena and Reggio Emilia via Università 4 Modena Italy

Introduction: the demand for urgent obstetric and gynecology care has progressively increased: in the United States approximately 1.4 million gynecologic visits are made to the emergency department (ED) annually, while almost 75% of women make at least 1 unscheduled visit during pregnancy. Moreover, research has recently focused on setting standards in unscheduled care, and developing quality indicators to improve patients’ health. Therefore, we investigated the characteristics of women with acute gynecological or pregnancy complaints using quality indicators developed for emergency medicine, to better define the needs of this population and improve care. Methods: Retrospective cohort study on ED, and Obstetrics and Gynecology (ObGyn) triage visits, at a tertiary care hospital in Italy, during 2012. Data were analyzed with population-averaged logistic regression and Poisson regression. Results: When compared to the 33,557 ED visits, the 9245 ObGyntriage referrals were more frequently associated with pregnancy (≤12 weeks’ gestation, OR: 30.7, 95%CI;24.5 - 38.4;>12 weeks’ gestation, OR 81.2, 95%CI;64.8 - 101.4), vaginal bleeding (OR 156.6, 95%CI;82.7 - 294.4), diurnal (night access OR 0.87, 95% CI;0.78 - 0.96) and weekday access (holiday access OR 0.87, 95%CI;0.78 - 0.95), frequent users (recurrent ED visits IRR 0.87, 95%CI;0.83 - 0.9) and lower hospital admissions (ED admission OR 1.6, 95%CI;1.4 - 1.8). Conclusion: ObGyn triage patients differed from ED users, and were at higher risk of “crowding”. Such diversities should be considered to improve female healthcare services and allocate resources more efficiently.

关键词： Acute Care Obstetric Urgencies Gynecologic Urgencies Obstetrics and Gynecology Triage Emergency Department

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High resolution colonoscopy in a bowel cancer screening program improves polyp detection

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World Journal of Gastroenterology 2011年第38期17卷 4308-4313页

作者： Matthew R banks Rehan Haidry M Adil butt Lisa Whitley Judith Stein Louise Langmead Stuart L bloom Austin O' bichere sara McCartney Kalpesh basherdas Manuel Rodriguez-Justo Laurence b Lovat Department of Gastrointestinal Services University College London Hospitals NHS Foundation Trust Department of Histopathology University College London Hospitals NHS Foundation Trust

AIM： To compare high resolution colonoscopy （Olympus Lucera） with a megapixel high resolution system （Pentax HiLine） as an in-service evaluation. METHODS： Polyp detection rates and measures of performance were collected for 269 colonoscopy procedures. Five colonoscopists conducted the study over a three month period, as part of the United Kingdom bowel cancer screening program. RESULTS：There were no differences in procedure duration （x^2 p = 0.98）, caecal intubation rates （x^2 P = 0.67）, or depth of sedation （x^2 P = 0.64）. Mild discomfort was more common in the Pentax group （x^2 p = 0.036）. Adenoma detection rate was significantly higher in the Pentax group （x^2 test for trend P = 0.01）. Most of the extra polyps detected were flat or sessile adenomas. CONCLUSION： Megapixel definition colonoscopes improve adenoma detection without compromising other measures of endoscope performance. Increased polyp detection rates may improve future outcomes in bowel cancer screening programs.

关键词： High resolution colonoscopy bowel cancerscreening Polyp detection

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Electron Micrographic Representations of Mechanisms of Action of Murine Norovirus on ATCC TIb-71 Cells and Level of Gene Expression

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Advances in Microbiology 2023年第1期13卷 32-47页

作者： Uchenna b. Iloghalu sara E. Miller Akamu J. Ewunkem Janak R. Khatiwada Shurrita S. Davis Leonard L. Williams Department of biology North Carolina A&T State University Greensboro USA Department of biology Guilford College Greensboro USA Department of Pathology Duke University Durham USA Department of biological Sciences Winston-Salem State University Winston-Salem USA Center for Excellence in Post-Harvest Technologies Kannapolis North Carolina A&T State University Greensboro USA

Human noroviruses (HuNoV) are the number one cause of viral gastroenteritis worldwide resulting in a significant cause of morbidity and mortality in all age groups. However, despite the medical relevance of HuNoV, effective treatment against norovirus infection is yet to be developed. In this study, we investigated the anti-Noroviral activity of Hibiscus sabdariffa (HS) calyces and Zanthoxylum armatum (ZA) seeds using murine norovirus, a surrogate of human norovirus. The antiviral mechanisms of action were also examined using a gene expression studies and transmission electron microscopy. Our results showed that virus-infected cells were left potentially void of all the cell machineries whereas uninfected cells represent healthy normal and dividing cells. The infected treated cells with extracts showed restoration of the dense cytoplasm, cytoplasmic membrane, and the nucleus. These cells were also associated with the expression of ORF genes. This study demonstrates the antiviral properties of Hibiscus sabdariffa (HS) calyces and Zanthoxylum armatum (ZA) and thus indicates their potential as natural remedies to treat noroviruses.

关键词： Norovirus Plant Extracts Transmission Electron Microscope Prevention/Control

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