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Evolocumab in Pediatric heterozygous Familial hypercholesterolemia

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四川生理科学杂志 2021年第1期43卷 114-114页

作者： Raul D santos Lipid Clinic heart Institute University of Sao Paulo Medical School Hospital and Hospital Israelita Albert Einstein Sao Paulo Amgen Thousand Oaks CA Departments of Vascular Medicine Pediatrics Amsterdam UMC Amsterdam Cardiology Department Geneva University Hospital Geneva Biostatistics Department Amgen Cambridge Rare Diseases and Clinical Genetics Unit Academic Pediatric Department Bambino Gesu Children''s Hospital Lipid Clinic Department of Medicine Centre Hospitalier Universitaire de Quebec-Universite Laval Quebec Canada 2nd Department of Pediatrics Semmelweis University Budapest Hungary Department of Clinical Inherited Metabolic Disorders Birmingham Children''s Hospital Birmingham United Kingdom Department of Molecular Medicine Umberto I Hospital Sapienza University of Rome Rome Department of Internal Medicine Centres Hospitaliers Jolimont La Louviere Belgium Division of Pediatric Pulmonology Allergology and Endocrinology Department of Pediatrics and Adolescent Medicine Medical University of Vienna Vienna Clinical Lipidology and Rare Lipid Disorders Unit Community Genomic Medicine Centre and ECOGENE-21 Department of Medicine Universite de Montreal Chicoutimi QC Canada From the Lipid Clinic heart Institute University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein São Paulo (R.D.S.) Amgen Thousand Oaks CA (A.R. C.E.K A.H.) the Departments of Vascular Medicine (G.K.H. J.J.P.K.) and Pediatrics (A.W. I.L.) Amsterdam UMC Amsterdam the Cardiology Department Geneva University Hospital Geneva (F.M.) the Biostatistics Department Amgen Cambridge (I.B.) and the Department of Clinical Inherited Metabolic Disorders Birmingham Children''s Hospital Birmingham (S.S.) - both in the United Kingdom the Rare Diseases and Clinical Genetics Unit Academic Pediatric Department Bambino Gesù Children''s Hospital (A.B.) and the Department of Molecular Medicine Umberto I Hospital Sapienza University of Rome (C.S.) Rome the Lipid Clinic Depart

Background:Evolocumab,a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9,is widely used in adult patients to lower low-density lipoprotein(LDL)cholesterol *** effects in pediatric patients with heterozygous familial hypercholesterolemia are not ***:We conducted a 24-week,randomized,double-blind,placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial *** 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter(3.4 mmol per liter)or more and a triglyceride level of 400 mg per deciliter(4.5 mmol per liter)or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab(420 mg)or *** primary end point was the percent change in LDL cholesterol level from baseline to week 24;key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24.

关键词： cholesterol Evolocumab lipoprotein

Production and Recovery of Rhamnolipids Using Sugar Cane Molasses as Carbon Source

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Journal of Chemistry and Chemical Engineering 2010年第11期4卷 27-33页

作者： Ana Carmen santos Marcio Silva Bezerra heloize dos santos Pereira Everaldo Silvino dos santos GoreteRibeiro de Macedo Federal University of Rio Grande do Norte Center of Technology Chemical Engineering Department Biochemical Engineering Laboratory Campus Universitario Lagoa Nova 3000 CEP.＇59072-970 Natal Rio Grande do Norte Brazil

Biosurfactants were synthesized by Pseudomonas aeruginosa （P.A.）, using sugar cane molasses as carbon source. Assays were conducted in a shaker with agitation speed of 200 rpm, temperature of 38 ℃ and aeration ratio （Vm/Vf） of 0.4 and 0.6. A concentration of 3.0% was used for the carbon and energy source （molasses） and of 0.3% for the nitrogen source （NaNO3）. Samples were removed at regular times until 96 hours of cultivation. The reduction in surface tension was measured using the ring method; cell concentration was obtained by the dry mass and substrate consumption by the DNS method. The metabolite produced was extracted and quantified by the thioglycolic method. The results showed a maximum surface tension reduction of 46.57% after 60 h, 3.63 g/L of biomass after 8 h （μXmax =0.15 h^-1）, 79.60% of substrate consumption （μs= 0.67 h-1） and 4.47 g/L of rhamnolipid （μp=0.029 h^-1）.

关键词： Biosurfactants molasses rhamnolipids Pseudomonas aeruginosa.

The antiangiogenic phloroglucinol hyperforin inhibits the secretion of proMMP-2, proMMP-9 and VEGF-A during apoptosis of primary acute myeloid leukemia cells

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 588-603页

作者： Faten Merhi Ruoping Tang Ollivier Legrand Florence Nguyen-Khac santos A.Susin Brigitte Bauvois Centre de Recherche des Cordeliers INSERMSorbonne UniversitéUSPCUniversitéParis DescartesUniversitéParis DiderotParis F-75006France Department of Life&Earth Sciences Faculty of Sciences(I)Lebanese UniversityBeirutLebanon Assistance Publique-hôpitaux de Paris Groupe Hospitalier Saint-AntoineService d’Hématologie CliniqueParis F-75012France Service Génétique des Tumeurs Département de Biologie et de Pathologie MédicaleGustave Roussy Cancer CamusVillejuif F-94805France Assistance Publique-hôpitaux de Paris Groupe Hospitalier Pitié-SalpêtrièreService d’Hématologie BiologiqueParis F-75013France.

Aim:Angiogenesis is observed in acute myeloid leukemia(AML).AML cells abnormally proliferate and are resistant to *** regulators of angiogenesis,VEGF-A and matrix metalloproteinases(MMPs)2 and 9 are markers of disease status in *** natural phloroglucinol hyperforin(hF)displays antitumoral properties of potential pharmacological ***,we investigated the effects of hF on MMP-2/9 and VEGF-A expression and survival of primary AML ***:Blood and bone marrow samples were collected in 45 patients with distinct subtypes defined by French American British classification,i.e.,M0,M1,M2,M3,M4,and *** of MMPs and VEGF-A in leukemic blood cells and culture supernatants were determined by RT-PCR,ELISA,and gelatin zymography(MMPs).The balance between cell death and survival was assessed by flow cytometry with analysis of phosphatidylserine externalization and caspase-3 ***:The administration of hF promoted a caspase-associated apoptosis in primary AML blasts(from blood and bone marrow),but not normal blood cells and *** addition,hF inhibited the levels of secreted proMMP-2,proMMP-9,and VEGF-A without altering *** induction of apoptosis by hF significantly paralleled the inhibition of MMP-2/9 and VEGF-A release by *** differences were seen in response to the deleterious effects of hF between AML cells of distinct ***:Our results suggest that hF,through its proapoptotic and potential antiangiogenic properties(by inhibiting MMP-2/9 and VEGF-A)on primary AML cells,might be a useful experimental agent,in combination with existing drugs,for new therapeutic approaches in the treatment of this incurable disease.

关键词： Acute myeloid leukemia apoptosis hyperforin matrix metalloproteinase VEGF secretion

Mussel-Inspired and Bioclickable Peptide Engineered Surface to Combat Thrombosis and Infection

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Research 2022年第3期2022卷 91-104页

作者： Xiaohui Mou hongbo Zhang hua Qiu Wentai Zhang Ying Wang Kaiqin Xiong Nan huang hélder A.santos Zhilu Yang Affiliated Dongguan hospital Southern Medical UniversityDongguanGuangdong 523059China Guangdong Provincial Key Laboratory of Shock and Microcirculation GuangzhouGuangdong 510080China Key Laboratory of Advanced Technologies of Materials Ministry of EducationSchool of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Pharmaceutical Sciences Laboratory Åbo Akademi UniversityTurku Biosciences CenterUniversity of Turku andÅbo Akademi University20520 TurkuFinland State Key Laboratory of Molecular Engineering of Polymers Fudan UniversityShanghai 200438China Department of Biomedical Engineering and W.J.Kolff Institute for Biomedical Engineering and Materials Science University Medical Center Groningen/University of GroningenAnt.Deusinglaan 19713 AV GroningenNetherlands Drug Research Program Division of Pharmaceutical Chemistry and TechnologyFaculty of PharmacyUniversity of HelsinkiFI-00014 HelsinkiFinland

Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in *** address this issue,here,we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide,with bio-orthogonal click chemistry,to tailor the surface functionalities of tubing and *** by mussel adhesive foot protein,a bioclickable peptide mimic(DOPA)4-azidebased structure is designed and grafted on an aminated tubing robustly based on catechol-amine ***,the dibenzylcyclooctyne(DBCO)modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions and the DBCO-modified antimicrobial peptide(DBCO-AMP)are clicked onto the grafted surfaces via bio-orthogonal *** combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous snitrosothiols to resist adhesion/activation of platelets,thus preventing the formation of ***,this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.

关键词： DOTA generating Engine

ID7 Isolated from Bauhinia variegata Stem Inhibits Tumor Progression and Metastatic Mechanisms of Triple Negative Breast Cancer in Vivo

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Journal of Pharmacy and Pharmacology 2019年第7期7卷 368-384页

作者： Kamilla Monteiro dos santos Izabela Natalia Faria Gomes Renato JoséSilva Oliveira Fernanda E.Pinto Bruno Oliveira Fabrício P.Batista Rafael Cesar Russo Chagas hélio B.santos Ralph G.Thomé Wanderson Romao Rui Manuel Reis Maria Luiza Vilela Oliva Rosy Iara Maciel de Azambuja Ribeiro Laboratory of Experimental Pathology Federal University of Sao Joao del-Rei(UFSJ)DivinópolisMGBrazil Josédo Rosário Vellano University UnifenasDivinópolisMGBrazil Molecular Oncology Research Center(CPOM) Barretos Cancer HospitalBarretosSPBrazil Petroleomic and Forensic Chemistry Laboratory Department of ChemistryFederal Institute of Espírito Santo(IFES)VitóriaESBrazil Chemistry Department Federal University of Sao PauloBrazil Tissue Processing Laboratory Federal University of Sao Joao del-Rei(UFSJ)DivinópolisMGBrazil Life and health Sciences Research Institute(ICVS) Medical SchoolUniversity of MinhoBragaPortugal 3ICVS/3B’s-PT Government Associate Laboratory GuimaraesBragaPortugal

Background:The breast cancer has been the most common form of cancer among *** triple negative subtype represents 20%of all breast cancer cases in the world and is standing out by affecting young women and being *** main cause of death of patients with cancer is due to metastasis,which can reach the liver and ***:The activities of ID7 fraction of the stems of Bauhinia variegata *** breast cancer,lung metastasis and liver inflammatory process were ***:ID7 was characterized by *** viability of murine mammary cells(4T1)treated with ID7 was assessed by MTT,trypan blue and fluorescence assay and viability of BT-20,MDA-MB-231 and MCF-7 human breast cancer tumor lines by *** cell migration,invasion using matrigel and adhesion were *** expression of cell death proteins was quanitified by western blot and the gelatinases by *** ID7 activity of the tumor(4T1)and metastatic progession in vivo was ***:ID7 reduced the 4T1 and MDA-MB-231viability and increased the late apoptosis,inhibited the 4T1 migration and invasion,increased the 4T1 adhesion and decreased the secreted active ***7 also increased the expression of PARP,caspase-7 and caspase-8,RIP and *** vivo,the ID7 decreased the volume and weight of the tumors and decreased lung metastasis and inflammation in the *** characterization showed mainly the presence of oleic acid,myricetin,quercetin and kaempferol in ***:Thus,it was found that ID7 fraction exhibits selective antitumor and on the mechanisms of breast cancer metastasis activity,preventing lung metastasis and inflammation in the *** is suggested that fatty acids and flavonoids are correlated with such activities.

关键词： 4T1 cells MDA-MB-231 medicinal plants kaempferol gelatinases apoptosis cell viabilty in vivo

Catalytic performance of zinc-supported copper and nickel catalysts in the glycerol hydrogenolysis

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Journal of Energy Chemistry 2020年第3期29卷 185-194页

作者： R.J.Chimentao B.C.Miranda D.Ruiz F.Gispert-Guirado F.Medina J.Llorca J.B.O.santos Physical Chemistry Department Faculty of Chemical SciencesUniversity of ConcepcionCasilla 160-CConcepcionChile Chemical Engineering School Universidad de Costa Ric1San Jose 2060Costa Rica Scientific Resources Service Universitat Rovira i VirgiliTarragona 43007Spain Department of Chemical Engineering Universitat Rovira i VirgiliTarragona 43007Spain Department of Chemical Engineering Barcelona Research Center in Multiscale Science and EngineeringInstitute of Energy TechnologiesUniversitat Politècnica de Cataluny1EEBE08019 Barcelon1Spain Department of Chemical Engineering Universidade Federal de Sao Carlos(UFSCAR)Sao CarlosBrazil

Gas-phase catalytic conversion of glycerol to value added chemicals was investigated over zinc-supported copper and nickel *** addition of aluminum in the support was also investigated in glycerol conversion and the results indicate an increase in the acidity and adsorption capacity for both copper and nickel *** and XRD analysis revealed Ni Zn alloy formation in the Ni/ZnO *** XRD patterns of the prepared Zn Al mixed oxide catalysts show the presence of Gahanite phase(ZnAl2O4).In addition,h2 chemisorption and TPR results suggest a strong metal-support interactions(SMSI)effect between Ni and Zn O *** supports Zn O and ZnAl(Zn/Al=0.5)were investigated in the glycerol conversion and they did not present *** supported on ZnO and ZnAl mixed oxide(Zn/Al=0.5)was active towards hydroxyacetone *** was active in the hydrogenolysis of glycerol both for C–C and C–O bonds cleavage of glycerol producing *** metal-support interactions(SMSI)between Ni and ZnO has a remarkable suppression effect on the methanation activity during the glycerol conversion.

关键词： Glycerol hydrogenolysis Dehydration hydroxyacetone Copper Nickel Catalyst

Polyphenolic composition, antibacterial, modulator and neuroprotective activity of Tarenaya spinosa(Jacq.) Raf.(Cleomaceae)

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Asian Pacific Journal of Tropical Biomedicine 2019年第1期9卷 12-17页

作者： Francisca Samara Muniz dos santos Jose Weverton Almeida Bezerra Jean Paul Kamdem Aline Augusti Boligon Marli Matiko Anraku Ana Raquel Pereira da Silva Kleber Ribeiro Fidelis Nadghia Figueiredo Leite Antonio Ivanildo Pinho henrique Douglas Melo Coutinho Jose Edilson Goncalves dos santos Microscopy Laboratory Regional University of Cariri (URCA) Program Post graduate in Plant Biology (UFPE) Phytochemical Laboratory Department of Industrial Pharmacy Federal University of Santa Maria (UFSM) Microbiology and Molecular Biology Laboratory Regional University of Cariri (URCA)

Objective: To evaluate the antibacterial activity and neuroprotective capacity of the ethanolic and aqueous extracts of Tarenaya spinosa(T. spinosa) as well as to determine and quantify some of its polyphenols by high performance liquid chromatography with diode-array detection(hPLC-DAD). Methods: The bacterial Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa strains, grown in heart Agar Infusion, were tested. The drugs gentamicin, norfloxacin and imipenem were used to evaluate the modulating or antagonistic capacity of the T. spinosa extracts. The extract was analysed by hPLC-DAD to determine the main phenolic compounds. For the cell viability tests, individual heads of the Nauphoeta cinerea arthropod model were removed, homogenized in Trifluoromethyl ketone and centrifuged afterwards. Subsequently, 20 μL of NaN O2 were added to the biological material, except in the control group, to evaluate the protection capacity of the extracts. The homogenate of the insect heads was incubated for 2 h in tubes containing tetrazolium bromide. Results: hPLC-DAD demonstrated that the ethanolic extract of T. spinosa presented caffeic acid as the major compound. The ethanolic extract also showed neuroprotective effects at concentrations ≥ 10 μg/mL, while aqueous extract was shown to have a protective effect only at the concentration of 100 μg/mL. The aqueous extract demonstrated a clinically relevant antibacterial activity against the Staphylococcus aureus multidrug resistant strain-MDR, with MIC 512 μg/m L. however, when the extracts were associated with gentamicin and imipenem, a synergism was detected against Staphylococcus aureus and Escherichia coli MDR strains. Conclusions: Although it does not present an antibacterial action, the extracts of T. spinosa can be used in the pharmaceutical industries since its extracts show modulating action of drugs. Besides, these natural products have neuroprotective capacity.

关键词： Tarenaya spinosa Cleome spinose Nauphoeta cinerea Synergism Antibiotic resistance

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features

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World Journal of Gastroenterology 2017年第37期23卷 6854-6867页

作者： Diego Marques Layse Raynara Ferreira-Costa Lorenna Larissa Ferreira-Costa Romualdo da Silva Correa Aline Maciel Pinheiro Borges Fernanda Ribeiro Ito Carlos Cesar de Oliveira Ramos Raul hernandes Bortolin André Ducati Luchessi Andrea Ribeiro-dos-santos Sidney santos Vivian Nogueira Silbiger Laboratório de Bioanálise e Biotecnologia Molecular Universidade Federal do Rio Grande do Norte Programa de Pós-graduacao em Ciências Farmacêutica Universidade Federal do Rio Grande do Norte Laboratório de Genética humana e Médica Universidade Federal do Pará Departamento de Cirurgia Oncológica Liga Norte Riograndense Contra o Cancer Laboratório de Patologia eCitopatologia Liga Norte Riograndense Contra o Cancer Depart-amento de Análises Clínicas e Toxicológicas Universidade Federal do Rio Grande do Norte Núcleo de Pesquisas em Oncologia Universidade Federal do Pará

AIM To investigate the association between 16 insertiondeletions(INDEL) polymorphisms, colorectal cancer(CRC) risk and clinical features in an admixed *** O n e h u n d re d a n d fo r ty p a t i e n t s w i t h C R C a n d 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on Gene Mapper ID v3.2. Clinicopathological data were obtained by consulting the patients' clinical charts, intra-operative documentation, and pathology *** Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis(TNM) stage risk, the Ins alleles of ACE, hLAG and TP53(6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, hLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death *** The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, hLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.

关键词： Colorectal cancer Ins-del polymorphism Admixed population Potential biomarker Diagnostic Risk stratification Prognostic Clinical features

Auriculotherapy in primary health care: A large-scale educational experience in Brazil

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Journal of Integrative Medicine 2019年第4期17卷 302-309页

作者： Charles Dalcanale Tesser Ari Ojeda Ocampo More Melissa Costa santos Emiliana Domingues Cunha da Silva Fatima Terezinha Pelachini Farias Lucio Jose Botelho Department of Public health Federal University of Santa Catarina Floriandpolis Santa Catarina 88036-800 Brazil Post-graduate Program in Public health Federal University of Santa Catarina Florianopolis Santa Catarina 88036-800 Brazil Integrative Medicine and Acupuncture Service University Hospital Federal University of Santa Catarina Floriandpolis Santa Catarina 88036-800 Brazil Floriandpolis Municipality health Office Florianopolis Santa Catarina 88036-800 Brazil

Auriculotherapy consists of physical stimuli applied to the outer ear and is commonly associated with traditional Chinese medicine (TCM). The authors present and discuss the development of a course that offers a semi-on-site auriculotherapy course for Brazilian primary health care (PhC) professionals. The course was funded by the Brazilian Ministry of health and developed at the Federal University of Santa Catarina in 2015 by a team of experts in auriculotherapy. It consisted of 75 h of distance learning (five sequential modules) and 5 h of on-site learning. The modules included the following items:(1) introduction to integrative practices;(2) ear reflexology;(3) introduction to TCM;(4) biomedical view of auriculotherapy;and (5) auriculotherapy in PhC. The teaching material in eluded a workbook for each module, 14 video lectures and an interactive ear(on line resource) to study location and application to the main auricular points. The on-site lectures follow a structured script of ear palpation techniques, auricular seed insertion practice and clinical case discussions, under the supervision of trained instructors. The course was offered in 2016 and 2017 and on-site lectures took place in 25 cities, covering all Brazilian regions, in coordination with municipal or state boards of health. A total of 4273 health professionals concluded the training and their evaluation of the course was highly positive. The Brazilian experience of large-scale training shows the potential to disseminate auriculotherapy in the context of PhC, given that its practice is fast, easy to learn, safe, effective for different health problems and well accepted by the patients.

关键词： Auriculotherapy Traditional Chinese medicine Primary health care health education Distance learning