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Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells

World Journal of Clinical Oncology 2022年第6期13卷 505-519页

作者： Alejandro Español Yamila Sanchez agustina salem Jaqueline Obregon Maria Elena Sales Laboratory of Immunopharmacology and Tumor Biology CEFYBO CONICET University of Buenos AiresBuenos Aires C1121ABGArgentina

BACKGROUND Triple negative breast cancer is more aggressive than other breast cancer subtypes and constitutes a public health problem worldwide since it has high morbidity and mortality due to the lack of defined therapeutic *** to chemotherapy complicates the course of patients’*** authors have highlighted the participation of nicotinic acetylcholine receptors(nAChR)in the modulation of conventional chemotherapy treatment in cancers of the ***,in breast cancer,less is known about the effect of nAChR activation by nicotine on chemotherapy treatment in smoking *** To investigate the effect of nicotine on paclitaxel treatment and the signaling pathways involved in human breast MDA-MB-231 tumor *** Cells were treated with paclitaxel alone or in combination with nicotine,administered for one or three 48-h *** effect of the addition of nicotine(at a concentration similar to that found in passive smokers’blood)on the treatment with paclitaxel(at a therapeutic concentration)was determined using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide *** signaling mediators involved in this effect were determined using selective *** also investigated nAChR expression,and ATP“binding cassette”G2 drug transporter(ABCG2)expression and its modulation by the different treatments with Western *** effect of the treatments on apoptosis induction was determined by flow cytometry using annexin-V and 7AAD *** Our results confirmed that treatment with paclitaxel reduced MDA-MB-231 cell viability in a concentration-dependent manner and that the presence of nicotine reversed the cytotoxic effect induced by paclitaxel by involving the expression of functionalα7 andα9 nAChRs in these *** action of nicotine on paclitaxel treatment was linked to modulation of the protein kinase C,mitogen-activated protein kinase,extracellular signal-regulated kinase,and NF-κB signaling pathways,

关键词： Breast cancer Paclitaxel Nicotinic acetylcholine receptors Drug therapy Signal transduction Drug transporter

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Breast cancer:Muscarinic receptors as new targets for tumor therapy

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World Journal of Clinical Oncology 2021年第6期12卷 404-428页

作者： Alejandro Español agustina salem Yamila Sanchez María Elena Sales Laboratory of Immunopharmacology and Tumor Biology CEFYBO CONICET University of Buenos AiresBuenos Aires C1121ABGArgentina

The development of breast cancer is a complex process that involves the participation of different *** authors have demonstrated the overexpression of muscarinic acetylcholine receptors(mAChRs)in different tumor tissues and their role in the modulation of tumor biology,positioning them as therapeutic targets in *** conventional treatment for breast cancer involves surgery,radiotherapy,and/or *** latter presents disadvantages such as limited specificity,the appearance of resistance to treatment and other side *** prevent these side effects,several schedules of drug administration,like metronomic therapy,have been *** therapy is a type of chemotherapy in which one or more drugs are administered at low concentrations ***,two chemotherapeutic agents usually used to treat breast cancer have been considered able to activate *** combination of low concentrations of these chemotherapeutic agents with muscarinic agonists could be a useful option to be applied in breast cancer treatment,since this combination not only reduces tumor cell survival without affecting normal cells,but also decreases pathological neo-angiogenesis,the expression of drug extrusion proteins and the cancer stem cell *** this review,we focus on the previous evidences that have positioned mAChRs as relevant therapeutic targets in breast cancer and analyze the effects of administering muscarinic agonists in combination with conventional chemotherapeutic agents in a metronomic schedule.

关键词： Muscarinic receptors Drug therapy Breast cancer Drug combination Metronomic therapy Drug resistance

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Characterization of Arroyo Verde Epithermal Deposit:Paragenesis,Mineral Geochemistry,Geochronology and Fluid Inclusions in Lower Chon Aike Volcanism,Argentina

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Journal of Earth Science 2024年第1期35卷 62-84页

作者： Cecilia Pavón Pivetta Leonardo Benedini Paulo Marcos Ma.agustina Cócola Mercedes Virginia Barros Daniel Gregori Leonardo Strazzere Anderson Costa dos Santos Mauro C.Geraldes Instituto Geologico del Sur(INGEOSUR) Universidad Nacional del Sur(UNS)-Consejo Nacional de Investigaciones Cientificas y Tecnicas(CONICET)Bahia Blanca 8000Argentina Dpto.de Geologia Universidad Nacional del Sur(UNS)Bahia Blanca 8000Argentina Universidad Nacional de Rio Negro Instituto de Investigacion en Paleobiologia y GeologiaGeneral Roca 8332Argentina Universidade do Estado do Rio de Janeiro Faculdade de GeologiaDepartamento de Mineralogia e Petrologia igneaRiodeJaneiro20559-900Brazil Geobiotec Departamento de GeocienciasUniversidade de AveiroAveiro 3800-002Portuga

Arroyo Verde epithermal deposit,in the North Patagonia region of Argentina,is located within the Lower Chon Aike volcanism and is developed between 192.6±2.5 Ma(mineralization host rock)and 189.5±2.6 Ma(overlying lava).Marifil volcanic complex is the host rock for these veins,veinlets and *** particular small deposit has developed low to intermediate sulphidation characteristics,with gangue mineral textures associated with several ore *** probe microanalysis determines electrum,silver minerals such as acanthite,and tetrahedrite,related Ag-Cu minerals like jalpaite,mckinstryite,stromeyerite,and base metals like chalcopyrite,sphalerite,galena and *** inclusions in quartz of two out of five events indicate that these Low Jurassic veins were formed due to subtle boiling and dilution mechanisms and by low-salinity(3.4 wt.%to 6.7 wt.%NaCl Eq)magmatic-hydrothermal fluid at 225 to 310℃.The fluid inclusion measurements that indicate boiling(Event 3)were plotted,and based on this data,we interpret that the Arroyo Verde deposit has been eroded between 550 and 700 *** particular character has not been previously recorded for other sectors of the eastern north Patagonian region.

关键词： epithermal deposit Ag minerals mineral geochemistry fluid inclusions Chon Aike geochronology

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Load dependent microstructural evolution in an as-cast 26%Cr high chromium cast iron during unlubricated sliding

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Friction 2022年第8期10卷 1258-1275页

作者： U.Pranav NAYAK Sebastian SUÁREZ Valentin PESNEL Frank MÜCKLICH María agustina GUITAR Department of Materials Science Saarland UniversitySaarbrücken 66123Germany Materials Engineering Center Saarland Saarbrücken 66123Germany Ecole Européenne d’ingénieurs en Génie des Matériaux Universitéde LorraineNancy 54000France

In the current study,an as-cast 26%Cr high chromium cast iron(HCCI)alloy was subjected to dry-sliding linear wear tests,under different *** loads were selected based on analytically computing the critical load(PC)i.e.,the load necessary to induce plastic *** PC was calculated to be 15 N and accordingly,a sub-critical load(5 N)and an over-critical load(20 N)were *** influence of increasing the load during the wear test was investigated in terms of the matrix microstructural behaviour and its ability to support the surrounding *** morphological aspects of the wear tracks,and the deformed matrix microstructure adjacent and underneath the track was analysed by confocal laser scanning microscope(CLSM)and scanning electron microscope(SEM),*** evidence of plastic deformation of the matrix was observed below *** the contrary,at loads equal to and higher than PC,the austenitic matrix plastically deformed as evidenced by the presence of slip *** backscattered diffraction(EBSD)measurements in terms of grain reference orientation deviation,and micro-Vickers hardness of the austenitic matrix indicated a deformation depth of about 40μm at the maximum applied load of 20 *** active wear mechanisms during sliding were a combination of both adhesive and abrasive wear,although increasing the load shifted the dominant mechanism towards *** was primarily attributable to the increased propensity for carbide cracking and fracturing,combined with the inability of the hardened austenitic matrix surface and sub-surface to adequately support the broken carbide ***,the shift in the dominant wear mechanism was also reflected in the wear volume and subsequently,the wear rate.

关键词： high chromium cast iron unlubricated sliding plastic deformation wear resistance carbide spallation matrix hardness

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Influence of structural depth of laser-patterned steel surfaces on the solid lubricity of carbon nanoparticle coatings

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Friction 2023年第7期11卷 1276-1291页

作者： Timothy MACLUCAS Lukas DAUT Philipp GRÜTZMACHER Maria agustina GUITAR Volker PRESSER Carsten GACHOT Sebastian SUAREZ Frank MÜCKLICH Chair of Functional Materials Saarland UniversitySaarbrücken 66123Germany Institute for Engineering Design and Product Development TU WienWien 1060Austria INM–Leibniz Institute for New Materials Saarbrücken 66123Germany Department of Materials Science&Engineering Saarland UniversitySaarbrücken 66123Germany Saarene-Saarland Center for Energy Materials and Sustainability Saarbrücken 66123Germany

Carbon nanoparticle coatings on laser-patterned stainless-steel surfaces present a solid lubrication system where the pattern's recessions act as lubricant-retaining *** study investigates the influence of the structural depth of line patterns coated with multi-walled carbon nanotubes(CNTs)and carbon onions(COs)on their respective potential to reduce friction and *** laser interference patterning(DLIP)with a pulse duration of 12 ps is used to create line patterns with three different structural depths at a periodicity of 3.5μm on AISI 304 steel ***,electrophoretic deposition(EPD)is applied to form homogeneous carbon nanoparticle coatings on the patterned *** ball-on-disc experiments are conducted on the as-described surfaces with an alumina counter body at a load of 100 *** results show that the shallower the coated structure,the lower its coefficient of friction(COF),regardless of the particle ***,with a minimum of just below 0.20,CNTs reach lower COF values than COs over most of the testing *** resulting wear tracks are characterized by scanning electron microscopy,transmission electron microscopy,and energy-dispersive X-ray *** friction testing,the CNTs remain in contact,and the immediate proximity,whereas the CO coating is largely *** of structural depth,no oxidation occurs on CNT-coated surfaces,whereas minor oxidation is detected on CO-coated wear tracks.

关键词： solid lubricant coatings carbon nanotubes carbon onions direct laser interference patterning(DLIP)surface structuring electrophoretic deposition(EPD)

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Impact of chitosan-based nanocarriers on cytoskeleton dynamics:Current status and challenges

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BIOCELL 2022年第4期46卷 885-891页

作者： M.CAROLINA DI SANTO agustina ALAIMO ANA PAULA DOMÍNGUEZ RUBIO OSCAR E.PÉREZ Departamento de Química Biológica Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales Consejo Nacional de Investigaciones Científicas y Técnicas(IQUIBICENCONICET)Buenos AiresArgentina

Chitosan-based nanocarriers(CS-NCs)show a promising role in improving drugs and bioactive compounds delivery for ***,the effects exerted by CS-NCs at the cellular level,including their recognition and uptake,have not been fully investigated *** factors,including size,shape,concentration,and surface chemistry of CS-NCs,play an important role in determining the types of intracellular signals *** mechanism of uptake and the involvement of the cytoskeleton during the CS-NCs endocytosis variates among the different cell types as well as further effects observed inside *** the present work,we discuss the effects induced by CS-NCs per se on the cytoskeleton,a key component in cell architecture and *** focus of this report is made on tumoral and normal biological models in which CS-NCs could differentially affect the cell *** recent years reports regarding the impact of CS-NCs on cytoskeleton dynamics and the current techniques for its evaluation are summarized and *** mechanisms underlying cytoskeletal impact after cell exposure to CS-NCs is critical for the design of safest value-added formulations in the biomedical ***,this revision points out some interesting aspects of cytoskeletal changes and cell death encompassing anti-tumoral effects.

关键词： Cytoskeletal dynamics Cellular uptake Endocytosis Nanocarriers Chitosan Bioactive compounds

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Anticancer drug screening of natural products:In vitro cytotoxicity assays,techniques,and challenges

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Asian Pacific Journal of Tropical Biomedicine 2022年第7期12卷 279-289页

作者： agustina Setiawati Damiana Sapta Candrasari F.D.Erika Setyajati Vincentia Krisnina Prasetyo Dewi Setyaningsih Yustina Sri Hartini Faculty of Pharmacy Sanata Dharma UniversityPainganMaguwoharjoDepokSlemanYogyakarta 55282Indonesia

Natural products include several diverse compounds that have been found to be effective against *** anticancer compounds in nature is a multistep and complex process that requires pre-clinical and clinical *** a few of the available natural products are used to treat cancer since most of them have very high complexity and low ***,the process of anticancer drug discovery requires a straightforward and effective method to assess anticancer activity using in vitro *** review summarizes various cell-based assays and techniques used to measure cell viability,migration,and apoptosis,focusing in particular on the principles,mechanisms,advantages,and disadvantages of each assay to provide a preliminary platform for cancer drug discovery.

关键词： Drug discovery Cancer Natural products Screening In vitro assay Cytotoxicity Migration Apoptosis

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Therapeutic effect of soluble worm protein acting as immune regulatory on colitis

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Asian Pacific Journal of Tropical Biomedicine 2017年第1期7卷 70-77页

作者： agustina Tri Endharti Aswin Djoko Baskoro Eviana Norahmawati Department of Parasitology Faculty of MedicineBrawijaya UniversityMalang 65145East JavaIndonesia Department of Pathology Anatomy Faculty of MedicineBrawijaya UniversityMalang 65145East JavaIndonesia

Objective: To investigate the anti-inflammatory effect of the protein derived from the soluble factor of Heligmosomoides polygyrus(H. polygyrus) excretory-secretory in a colitis ***: Colitis was induced by providing drinking water containing 3% dextran sodium sulfate(DSS) for a week. DSS was administrated in a cycle protocol, each cycle consisted of 7 days of 3% DSS in the drinking water and followed by 7 days of regular water. This study consisted of five treatment groups, including Groups A(control)received untreated water, B(DSS only, without excretory-secretory), and C–E injected(i.p.) with excretory-secretory protein(H. polygyrus excretory-secretory total, excretorysecretory 28 k Da and excretory-secretory 55 k Da, respectively). Mice received injection every week. The injection of excretory-secretory was started from the 6th weeks and continued until 11 weeks. At the end of 11 weeks of the experiment, mice were sacrificed,colon tissue was removed and then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, flow cytometry, real-time PCR and histology ***: Mice received H. polygyrus excretory-secretory 55 k Da reduced mono-nuclear cell infiltrations. H. polygyrus excretory-secretory 55 k Da induced the down-regulation of m RNA interferong expression. There were significant differences in the expression of m RNA interferon in the colon of mice after the administration of the excretory-secretory55 k Da protein fraction compared with other groups(P < 0.001), whereas m RNA transforming growth factorb expression up regulated in the colon of mice after the administration of the excretory-secretory 55 k Da protein fraction compared with total excretory-secretory group(P < 0.05). The treatment of colitis in mice with excretorysecretory 55 k Da protein fractions modulated interleukin-10(IL-10) expression,whereas excretory-secretory total and excretory-secretory 28 k Da protein fractions insufficient promoted IL-10 expression.

关键词： Colitis Excretory-secretory Heligmosomoides polygyrus Soluble protein

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3-D crustal-scale gravity model of the San Rafael Block and Payenia volcanic province in Mendoza,Argentina

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Geoscience Frontiers 2018年第1期9卷 239-248页

作者： Daniel Richarte Marianela Lupari agustina Pesce Silvina Nacif Mario Gimenez Instituto Geofísico-Sismológico Volponi Universidad Nacional de San JuanArgentina Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET) Argentina

The San Rafael Block(SRB)is part of one of the main retroarc volcanic provinces in southern Central Andes in Mendoza,*** block is located in the Andean foothills between the orogenic front and foreland basement uplifts of late Miocene *** order to analyze the geochronological evolution of the Quaternary volcanism in the region,several geologic and geophysical studies have been ***,the crust,where the SRB is located,has not been well characterized *** on gravimetric and magnetic data,together with isostatic and elastic thickness analyses,we modeled the crustal structure of the *** obtained has allowed us to understand the crust where the SRB and the Payenia volcanic province are *** anomalies indicate that the SRB presents higher densities to the North of Cerro Nevado and Moho calculations suggest depths for this block between 40 and 50 *** of elastic thickness would indicate that the crust supporting the San Rafael Block presents values of approximately 10 km,being enough to support the block ***,in the Payenia region,elastic thickness values are close to zero due to the regional temperature increase.

关键词： San Rafael Block Payenia 3-D crustal model Asthenospheric wedge

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The inhibition of Typhonium flagelliforme Lodd. Blume leaf extract on COX-2 expression of Wi Dr colon cancer cells

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Asian Pacific Journal of Tropical Biomedicine 2016年第3期6卷 251-255页

作者： agustina Setiawati Handika Immanuel Mery Tri Utami Department of Drug Design and Discovery Faculty of Pharmacy Sanata Dharma University

Objective: To determine the inhibition activity of Typhonium flagelliforme Lodd. Blume(T. flagelliforme) leaf extract on cyclooxygenase 2(COX-2) expression of colon cancer ***: T. flagelliforme leaf extract was prepared to macerate in ethyl acetate. In vitro anticancer activity was assayed by MTT method on Wi Dr colon cancer cells. This study applied apoptosis induction assay to investigate the mechanism of cell death using double staining method. COX-2 expression was stained by ***: T. flagelliforme showed anticancer activity and induced apoptosis on Wi Dr cells through inhibition of COX-2 expression with IC5070 mg/m ***: This study showed that T. flagelliforme is a promising chemopreventive agent for colon cancer through COX-2 inhibition.

关键词： Typhonium flagelliforme Colon cancer WiDr Cyclooxygenase 2

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