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Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells

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Biophysics Reports 2019年第1期5卷 19-30页

作者： Seyed Mohammad Motevalli Ahmed Shaker Eltahan Lu Liu andrea magrini Nicola Rosato Weisheng Guo Massimo Bottini Xing-Jie Liang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China University of Chinese Academy of Sciences Department of Experimental Medicine University of Rome Tor Vergata Department of Biomedicine and Prevention University of Rome Tor Vergata Nanoscience & Nanotechnology & Innovative Instrumentation (NAST) Centre University of Rome Tor Vergata Inflammatory and Infectious Disease Center Sanford-Burnham Medical Research Institute

The adaptive treatment tolerance(ATT) of cancer cells is the main encumbrance to cancer chemotherapy.A potential solution to this problem is to treat cancer cells with multiple drugs using nanoparticles(NPs).In this study, we tested the co-administration of curcumin(Cur) and doxorubicin(Dox) to MCF-7 resistant breast cancer cells to block the ATT and elicit efficient cell killing. Drugs were co-administered to cells both sequentially and simultaneously. Sequential drug co-administration was carried out by pre-treating the cells with albumin nanoparticles(ANPs) loaded with Cur(Cur@ANPs) followed by treatment with Dox-loaded ANPs(Dox@ANPs). Simultaneous drug co-administration was carried out by treating the cells with ANPs loaded with both the drugs(Cur/Dox@ANPs). We found that the simultaneous drug co-administration led to a greater intra-cellular accumulation of Dox and cell killing with respect to the sequential drug co-administration. However, the simultaneous drug co-administration led to a lower intracellular accumulation of Cur with respect to the sequential drug co-administration. We showed that this result was due to the aggregation and entrapment of Cur in the lysosomes as soon as it was released from Cur@ANPs, a phenomenon called lysosomotropism. In contrast, the simultaneous release of Dox and Cur from Cur/Dox@ANPs into the lysosomes led to lysosomal p H elevation, which, in turn, avoided Cur aggregation, led to lysosome swelling and drug release in the cytosol, and finally provoked efficient cell killing. Our study shed the light on the molecular processes driving the therapeutic effects of anti-cancer drugs co-administered to cancer cells in different manners.

关键词： Albumin nanoparticles Doxorubicin Curcumin P-glycoprotein Lysosomal pH

Smoking, ACP<sub>1</sub>and Infertility in Subjects with Varicocele

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Health 2019年第10期11卷 1331-1337页

作者： Anna Neri Maria Banci Adalgisa Pietropolli Fulvia Gloria-Bottini andrea magrini

Several studies suggest that smoking may have detrimental effect on seminal parameters and that genetic polymorphisms may influence this effect. In the present paper we have examined the relationship between ACP1 genotypes and the association of smoking and infertility in a sample of men with varicocele. 126 subjects with varicocele were studied. ACP1 genotype was determined by DNA analysis and statistical analyses were performed by SPSS software. In general there is a protective action of low activity *A/*B genotype against infertility that is much more marked in smokers than in non-smokers. If confirmed in other clinical settings, determinations of ACP1 genotype could have practical importance to evaluate the risk of infertility in smokers with varicocele.

关键词： Smoking ACP1 Varicocele Infertility Genetic Polymorphism

Adenylate kinase locus 1 genetic polymorphism and type 2 diabetes

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Health 2011年第2期3卷 77-81页

作者： Fulvia Gloria-Bottini Elena Antonacci Anna Neri andrea magrini Egidio Bottini 不详

AK1 catalyzes the reversible reaction ATP+AMP ? 2ADP thus contributing to the regulation of relative concentration of these important nu-cleotides. Intracellular ATP is a storage of en-ergy for cellular processes, moreover extracel-lular ATP together with ADP, AMP and adeno-sine are critical signalling molecule for sending messages to nearby cells acting on P1 and P2 receptors. AK1 shows a genetic polymorphism and recently our group has shown that the cor-relation between blood glucose and glycated haemoglobin in T2D is dependent on AK1 phe-notype. In the present paper we have carried further studies on the relationship between AK1 phenotypes and T2D. Possible interactions with ABO blood groups and ACP1 polymorphism have also been investigated. We have re-ex-amined the data on 280 subjects with type 2 diabetes from the White population of Penne (Central Italy). 384 consecutive healthy new-borns from the same population have been also studied. A three way contingency table analysis was carried out according to Sokal and Rohlf and other statistical analyses by SPSS pro-grams. T2D patients with AK12-1 phenotype have higher values of blood glucose level and glycated haemoglobin and an increased ten-dency to dyslipidemia and retinopathy. In addi-tion there is an interaction of AK1 with ABO blood groups and with ACP1 polymorphism. The different activity between AK1 phenotypes could influence the relative concentration of ATP, ADP, AMP and adenosine with important effects on metabolic activity thus explaining the associa-tion of AK1 with clinical manifestation of T2D.

关键词： AK T2D Glycemia ATP Glycated Haemoglobin

The association of adenosine deaminase with coronary artery disease: Effect of gender and diabetes

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Health 2013年第2期5卷 166-169页

作者： Fulvia Gloria-Bottini Krzysztof Safranow Maria Banci Agnieszka Binczak-Kuleta Patrizia Saccucci Andrzej Ciechanowicz andrea magrini Zdzislawa Kornacewicz-Jach Egidio Bottini Dariusz Chlubek Department of Biochemistry and Medical Chemistry Pomeranian Medical University Szczecin Poland Department of Biomedicine and Prevention School of Medicine University of Rome Tor Vergata Rome Italy Department of Cardiology Pomeranian Medical University Szczecin Poland Department of Cardiology Valmontone Hospital Valmontone Italy Department of Laboratory Diagnostics and Molecular Medicine Pomeranian Medical University Szczecin Poland

An association between ADA1 and Coronary Artery Disease (CAD) has been observed in Polish and in Italian populations but in Italian population the association was present in males only. In order to enlighten these differences we have carried out a collaborative study in the two populations. In Italy 215 subjects admitted to the Hospital for CAD, 275 subjects with Type 2 Diabetes (T2D) without CAD and 398 healthy new-borns were studied. In Poland 173 subjects with CAD and 200 healthy newborns were studied. Written informed consent was obtained from all subjects or from their mothers to participate to the study that was approved by the I.R.B. ADA1 polymorphism was determined by DNA analysis. Three way contingency table analysis was performed by a log linear model. The association between CAD and ADA1 is present in non diabetic male subjects only: OR = 0.195, p = 0.007 in the Italian population and OR = 0.163, p = 0.004 in the Polish population. The data suggest a significant role of immunological mechanisms in the pathogenesis of CAD without diabetes. Gender differences in immune diseases could explain the lack of association in females.

关键词： ADA CAD Gender Diabetes

Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia

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World Journal of Diabetes 2014年第4期5卷 557-561页

作者： Fulvia Gloria-Bottini Patrizia Saccucci Gian Franco Meloni Maria Luisa Manca-Bitti Luca Coppeta Anna Neri andrea magrini Bottini Egidio Department of Biomedi-cine and Prevention School of Medicine University of Rome Tor Vergata 00133 Rome Italy Department of Pediatrics University of Sassari Medical School 07010 Sassari Italy Pediatric Diabetology and Endocrinol-ogy Unit Policlinico Tor Vergata University Hospital 00144 Rome Italy

AIM:To investigate the role of protein tyrosin phosphatase 22(PTPN22),maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes(T1D)in Continental Italy and Sardinian populations.METHODS:Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia.PTPN22 genotype was determined by DNA analysis.Maternal age at conception and age at onset of disease were obtained from clinical records.χ2 test of independence,student t test for differences between means and odds ratio analysis were carried out by SPSS programs.Three way contingency table analysis was carried out according to Sokal and Rohlf.RESULTS:The pattern of association between PTPN22and T1D is similar in Continental Italy and Sardinia:the proportion of*T allele carriers is 13.6%in T1D vs6.7%in controls in Continental Italy while in Sardinia is 7.3%in T1D vs 4.4%in controls.The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy:the proportion of newborn from mother aging more than 32 years is89.3%in T1D vs 32.7%in consecutive newborn in Sardinia(P<10-6)while in Continental Italy is 32.2%in T1D vs 19.1%in consecutive newborns(P=0.005).This points to an important role of ethnicity.A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia.PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia.Maternal age does not influence significantly age at onset in Italy(8.2 years in T1D infants from mothers aging32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years:P=0.824)while in Sardinia a border line effect is observed(5.75 years in T1D infants from mothers aging 32 years or less vs7.54 years in T1D infants from mothers aging more than 32 years:P=0.062).No effec

关键词： Type 1 diabetes Continental Italy Sardinia Protein tyrosin phosphatase 22 Maternal age Age of onset Sex

Spatio-temporal coupled mode theory for nonlocal metasurfaces

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Light(Science & Applications) 2024年第2期13卷 267-282页

作者： Adam Overvig Sander A.Mann andrea Alù Photonics Initiative Advanced Science Research CenterCity University of New YorkNew YorkNY10031USA Physics Program Graduate Center of the City University of New YorkNew YorkNY10016USA

Diffractive nonlocal metasurfaces have recently opened a broad range of exciting developments in nanophotonics research and applications,leveraging spatially extended—yet locally patterned—resonant modes to control light with new degrees of freedom.While conventional grating responses are elegantly captured by temporal coupled mode theory,current approaches are not well equipped to capture the arbitrary spatial response observed in the nascent field of nonlocal metasurfaces.Here,we introduce spatio-temporal coupled mode theory(STCMT),capable of elegantly capturing the key features of the resonant response of wavefront-shaping nonlocal metasurfaces.This framework can quantitatively guide nonlocal metasurface design while maintaining compatibility with local metasurface frameworks,making it a powerful tool to rationally design and optimize a broad class of ultrathin optical components.We validate this STCMT framework against full-wave simulations of various nonlocal metasurfaces,demonstrating that this tool offers a powerful semi-analytical framework to understand and model the physics and functionality of these devices,without the need for computationally intense full-wave simulations.We also discuss how this model may shed physical insights into nonlocal phenomena in photonics and the functionality of the resulting devices.As a relevant example,we showcase STCMT’s flexibility by applying it to study and rapidly prototype nonlocal metasurfaces that spatially shape thermal emission.

关键词： theory resonant spatially

Proximity to corridors benefits bird communities in vegetated interrow vineyards in Mendoza, Argentina

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Avian Research 2024年第2期15卷 147-155页

作者： andrea Paula Goijman Agustín Zarco EEA La Consulta Instituto Nacional de Tecnología Agropecuaria(INTA)San CarlosMendozaArgentina Instituto Argentino de Investigacion en las Zonas Aridas(IADIZA)CONICET 5500MendozaArgentina

Management under ecological schemes and increasing habitat heterogeneity,are essential for enhancing biodiversity in vineyards.Birds provide several contributions to agriculture,for example pest control,recreation and enhancing human mental health,and have intrinsic value.Birds are also ideal model organisms because they are easy to survey,and species respond differently to agricultural land use at different scales.Vegetated borders of crops are key for many species of birds,and distance to the border have been found to be an important factor in vineyard-dominated agroecosystems.We evaluate if there are differences in the bird assemblage,between the interior compared to borders within vineyards,using a hierarchical community occupancy model.We hypoth-esized that occupancy of birds is greater in environments with greater heterogeneity,which in this study was considered to be contributed by the proximity to vegetated corridors.We expected that vineyard borders close to corridors will have higher bird occupancy than the center of the vineyard.The research was conducted in three vineyards with biodiversity-friendly management practices,in Gualtallary,Mendoza,Argentina.Bird surveys were conducted over three breeding seasons from 2018 to 2020.Occupancy and richness of the bird community was more closely associated with the borders adjacent to the corridors than with the interior of the vineyards,as we initially predicted,although the assemblage of birds did not differ much.More than 75%of the registered species consume exclusively or partially invertebrates.Biodiversity-friendly management and ecological schemes,together with vegetated corridors provide multiple benefits for biodiversity conservation.These ap-proaches not only minimize the use of agrochemicals but also prioritize soil cover with spontaneous vegetation,which supports a diverse community of insectivorous bird species,potentially contributing to pest control.

关键词： Avian Bayesian analysis Field scale agroecosystem Management Multi-species occupancy model Nature’s contributions to people

Design methodology of a mini-missile considering flight performance and guidance precision

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Journal of Systems Engineering and Electronics 2024年第1期35卷 195-210页

作者： ZHANG Licong GONG Chunlin SU Hua andrea Da Ronch Shaanxi Aerospace Flight Vehicle Design Key Laboratory School of AstronauticsNorthwestern Polytechnical UniversityXi’an 710072China Faculty of Engineering and Physical Sciences University of SouthamptonSouthampton SO171BJUnited Kingdom

The design of mini-missiles(MMs)presents several novel challenges.The stringent mission requirement to reach a target with a certain precision imposes a high guidance precision.The miniaturization of the size of MMs makes the design of the guidance,navigation,and control(GNC)have a larger-thanbefore impact on the main-body design(shape,motor,and layout design)and its design objective,i.e.,flight performance.Pursuing a trade-off between flight performance and guidance precision,all the relevant interactions have to be accounted for in the design of the main body and the GNC system.Herein,a multi-objective and multidisciplinary design optimization(MDO)is proposed.Disciplines pertinent to motor,aerodynamics,layout,trajectory,flight dynamics,control,and guidance are included in the proposed MDO framework.The optimization problem seeks to maximize the range and minimize the guidance error.The problem is solved by using the nondominated sorting genetic algorithm II.An optimum design that balances a longer range with a smaller guidance error is obtained.Finally,lessons learned about the design of the MM and insights into the trade-off between flight performance and guidance precision are given by comparing the optimum design to a design provided by the traditional approach.

关键词： mini-missiles(MMs) guidance navigation and control(GNC)system multi-objective optimization multidisciplinary design optimization(MDO) flight performance guidance precision

Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

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Neural Regeneration Research 2024年第12期19卷 2626-2636页

作者： Blanca Molins andrea Rodríguez Víctor Llorenç Alfredo Adán Group of Ocular Inflammation:Clinical and Experimental Studies Institut d’Investigacions Biomèdiques AgustíPi I Sunyer(IDIBAPS)BarcelonaSpain Institut Clínic d’Oftalmologia(ICOF) Hospital Clínic BarcelonaSpain

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

关键词： age-related macular degeneration Bruch's membrane decellularization retinal pigment epithelium scaffold