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Rapamycin-loaded nanostructured lipid carrier modified with folic acid intended for breast cancer therapy
No full textBreast cancer stands as the most common form of malignancy among women globally, and it showcases commendable rates of cure when detected in early-stage and non-metastatic conditions. To overcome drug resistance and side effects observed in conventional chemotherapy, the present study aims to deliver rapamycin (RAP), a mTOR protein inhibitor, into a nanostructured lipid carrier (NLC) functionalized with folic acid for promoting active targeting to breast cancer cells. In the first step, the synthesis of 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine-N-[amino(polyethylene glycol)-2000] (ammonium salt) with folic acid (DSPE-PEG2000-FA) was successfully performed and characterized by UV spectroscopy, nuclear magnetic resonance, and infrared spectroscopy. Then, the folic acid-modified NLC loaded with RAP (FA-NLC-RAP) and the unmodified formulation (NLC-RAP) was developed and displayed a size of about 100 nm, negative surface charge, and high RAP encapsulation efficiency (94.92 % and 85.72 %, respectively). In vitro studies suggested that FA-NLC-RAP exhibited a higher degree of internalization in cancer cells (MCF-7) than in normal cells (MCF-10A), demonstrating the potential of folic acid as a ligand for promoting active targeting of RAP for breast cancer cells through folate receptors overexpressed in tumor cells FA-NLC-RAP significantly reduced tumor cell viability, similarly to that observed with the RAP solution. The release profile of the formulation was prolonged. Finally, studies in Caenorhabditis elegans evidenced the safety of FA-NLC-RAP characterized by a complete absence of toxicity in this animal model. Therefore, the findings imply that FA-NLC-RAP holds considerable promise for the treatment of breast cancer.School of Pharmaceutical Science of São Paulo State University (UNESP), Sao PauloSchool of Pharmaceutical Science of São Paulo University (USP), Sao PauloSchool of Pharmacy University College London 29-39 Brunswick SquareUniversity of Navarra Department of Pharmaceutical SciencesSchool of Pharmaceutical Science of São Paulo State University (UNESP), Sao Paul
Assessment of the Osseointegration of Pure-Phase β-Tricalcium Phosphate (β-TCP) Ceramic Cylinder Implants in Critical Segmental Radial Bone Defects in Rabbits
No full textAutografts, allografts, and synthetic bone substitutes are essential in reconstructive orthopedic surgery. Although autografts and allografts provide excellent skeletal integration, their use is limited by host morbidity and graft acquisition challenges. Synthetic materials like β-tricalcium phosphate (β-TCP) offer promising osseoconductive properties as a potential substitute. This study evaluated the osseointegration of β-TCP ceramic cylinder implants in bone defects in rabbits. Eighteen New Zealand rabbits underwent radial diaphysis ostectomy to create a critical segmental defect and were divided into three groups: Group A received β-TCP blocks, Group B received allogenous cortical bone grafts, and Group C underwent ostectomy without defect filling. Postoperative assessments included clinical evaluations, radiographs, micro-computed tomography, and histology at various time points to assess osseointegration and implant resorption. At the 120th postoperative day, Group B showed successful bone integration without infection. In contrast, Group A showed no osseointegration or resorption of the β-TCP implants, and Group C exhibited bone non-union. While β-TCP demonstrated biocompatibility, it lacked osseoconductivity, likely due to low porosity. β-TCP implants did not promote bone consolidation, suggesting that further research on porosity and shape is needed to improve their suitability for veterinary orthopedic reconstructive surgery.Department of Surgery Faculty of Veterinary Medicine Federal University of Campina Grande (UFCG)Department of Surgery Animal Care Barueri Veterinary ClinicDepartment of Surgery School of Dentistry São Paulo State University (UNESP)Biomaterials Laboratory Institute for Energy and Nuclear Research National Nuclear Energy Commission IPEN/CNEN), São PauloDepartment of Surgery School of Dentistry São Paulo State University (UNESP
Parasitologistas veterinários: chegou a hora de falar sobre o uso das expressões “Protozoário” e “Protista”
No full textThe classification of eukaryotic organisms has evolved significantly over the past years. For a long time, the five-kingdom model proposed in 1969, which included the kingdoms Monera, Protista, Fungi, Plantae, and Animalia, dominated biological classification. However, recent advances in molecular biology, particularly phylogenomic studies, have challenged this classification as it does not accurately represent the evolutionary patterns of a vast diversity of organisms, especially those formerly known as protozoa. Currently, Protista is no longer considered a valid taxon, as the organisms previously classified in this group are highly divergent and not monophyletic. Modern approaches now classify eukaryotes into several supergroups, with protozoa now dispersed among different groups. For example, parasites once grouped as protozoa, such as Babesia (Apicomplexa), Trypanosoma (Euglenozoa), and Entamoeba (Evosea), are now placed into distant branches of the tree of life and within different supergroups. Although this supergroup classification may change in the coming years, it provides a more accurate representation of evolutionary relationships among eukaryotes. However, this issue has not been adequately discussed by the veterinary parasitology community. This article advocates revisiting these terms in light of modern classification systems to ensure a more accurate and biologically realistic terminology that reflects current knowledge.A classificação dos organismos eucarióticos evoluiu significativamente nos últimos anos. Por muito tempo, o modelo de cinco reinos proposto em 1969, que incluía os reinos Monera, Protista, Fungi, Plantae e Animalia, dominou a classificação biológica. No entanto, avanços na biologia molecular, desafiaram essa classificação, pois ela não representa o padrão evolutivo dos organismos, especialmente aqueles anteriormente conhecidos como protozoários. Atualmente, o termo Protista não é considerado um táxon válido, pois os organismos anteriormente classificados neste grupo são altamente distintos e não são monofiléticos. Abordagens modernas classificam os eucariotos em vários supergrupos, nos quais os protozoários são colocados em diferentes grupos. Por exemplo, parasitos anteriormente classificados como protozoários, como Babesia (Apicomplexa), Trypanosoma (Euglenozoa), Entamoeba (Evosea), são agora alocados em ramos distantes da árvore da vida e em diferentes supergrupos. Essa classificação de supergrupos oferece uma representação mais precisa das relações evolutivas entre os eucariotos e evidencia que a evolução (especialmente os organismos unicelulares) segue um padrão complexo de diversificação. Contudo, este tópico ainda não foi adequadamente discutido pela comunidade de parasitologistas veterinários. Este artigo propõe a revisão desses termos tendo em vista sistemas de classificação modernos, para garantir que parasitologistas veterinários e estudantes adotem uma terminologia mais precisa e biologicamente realista.Colégio Brasileiro de Parasitologia VeterináriaInstituto de Pesquisas Veterinárias Desidério Finamor, Secretaria de Agricultura do Estado do Rio Grande do SulUniversidade Federal FluminenseUniversidade Federal Rural do Rio de JaneiroInstituto Aggeu Magalhães, Fundação Oswaldo CruzUniversidade Estadual Paulista Júlio de Mesquita FilhoUniversidade Estadual de Santa CruzUniversidade Estadual Paulista Júlio de Mesquita Filh
Rendezvous Missions to Systems of Small Solar System Bodies Using the Suboptimal SDRE Control Approach
No full textIn this work, we analyze the suitability of the State-Dependent Riccati Equation (SDRE) suboptimal nonlinear control formulation for the implementation of body-fixed hovering of a spacecraft in the highly nonlinear environment engendered by the faint force fields around single- and multi-body Near-Earth Objects (NEOs), a class of Small Solar System Bodies with high relevance either in scientific, economic, or planetary defense-related aspects. Our results, addressing the hovering of a spacecraft around relative equilibrium points on the effective potential of the Near-Earth Asteroid (16) Psyche and of the much smaller main body (called Alpha) of the triple NEA system (153591) 2001SN263, show that the known effectiveness offered by the flexibility engendered by state-dependent factorization of nonlinear models is also effective when applied in these faint and highly nonlinear force fields. In fact, this work is a qualitative evaluation of the suitability of using SDRE in the highly disturbed environment around Small Solar System Bodies, which has never been undertaken before. We intend to prove that this method is adequate. For real missions, it is necessary to make deeper studies. In particular, our results show the flexibility granted by the SDRE approach in the trade off between maneuvering time against fuel consumption, a central aspect in such space missions. For instance, our simulations showed control effort and time of convergence for two controlled trajectories around (16) Psyche ranging from a half-time convergence with ∼20 times lower cost. Analogously, for the much smaller bodies in the (153591) 2001SN263 triple system, we got two trajectories in which one of them may converge ∼10 times faster but with up to ∼100 times higher cost.Ministry of Science and Higher Education of the Russian FederationAeronautics Institute of Technology—ITA Praça Marechal Eduardo Gomes, 50, SPFaculty of Engineering São Paulo State Univesity, Campus Bauru, Av Eng. Luiz E. C. Coube, 14-01SPDepartment of Production Engineering Federal University of Technology—Paraná (UTFPR), Campus Ponta Grossa, Rua Doutor Washington Subtil Chueire, 330PRPeoples’ Friendship University of Russia Named after Patrice Lumumba (RUDN University), 6, Miklukho-Maklaya Str.National Institute for Space Research—INPE, Av. dos Astronautas, 1758, SPFaculty of Engineering São Paulo State Univesity, Campus Bauru, Av Eng. Luiz E. C. Coube, 14-01SPMinistry of Science and Higher Education of the Russian Federation: FSSF-2024-000
Melatonin from Plants: Going Beyond Traditional Central Nervous System Targeting—A Comprehensive Review of Its Unusual Health Benefits
No full textMelatonin is indispensable for the homeostasis of plants and animals. In humans, it can help prevent or be an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of circadian rhythm, regulation of the immunological system, epilepsy control, delaying the aging process, and diminishing hormones related to cancer. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The results showed it can present scavenging of free radicals, reducing inflammatory cytokines, and modulating the immune system. Moreover, it can improve insulin resistance, blood pressure, LDL-c, adipose tissue mass, adhesion molecules, endothelial impairment, and plaque formation. These effects result in neuro- and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may be more cost-effective and present fewer adverse events than synthetic. However, more clinical trials should be performed to show adequate doses, formulation, and treatment time.Department of Biochemistry and Pharmacology School of Medicine Universidade de Marília (UNIMAR), SPPostgraduate Program in Structural and Functional Interactions in Rehabilitation School of Medicine Universidade de Marília (UNIMAR), SPDepartment of Biochemistry and Nutrition School of Food and Technology of Marília (FATEC), SPLaboratory of Systems Integration Pharmacology Clinical and Regulatory Science Research Institute for Medicines Universidade de Lisboa (iMed.ULisboa), Av. Prof. Gama PintoAutonomic Nervous System Center School of Philosophy and Sciences São Paulo State University, SPDepartment of Biochemistry and Pharmacology School of Medicine New York Medical CollegeDepartment of Biochemistry and Pharmacology School of Medicine University of MiamiDevelopment and Innovation Laboratory Butantan Institute, SPGraduate Program in Anatomy of Domestic and Wild Animals College of Veterinary Medicine and Animal Science University of São Paulo, SPTexas Institute for Kidney and Endocrine DisordersClinical Department School of Medicine University of Texas Medical BranchUNIMAR Charity Hospital Universidade de Marília (UNIMAR), SPAutonomic Nervous System Center School of Philosophy and Sciences São Paulo State University, S
Modeling reproductive and pregnancy-associated tissues using organ-on-chip platforms: challenges, limitations, and the high throughput data frontier
No full textOver the past decade, organ-on-chip technology (microphysiological systems or tissue chips) has reshaped in-vitro physiological and pathological modeling and pharmaceutical drug assessment. FDA Modernization Act 2.0 allows for alternatives to animal testing or the use of appropriate non-animal models/new approach methods (NAMs), such as Organ-on-chips (OC) platforms or in silico simulation models, to generate pre-clinical in-vitro drug trial data for regulatory purposes primes the microfluidic field to have exponential growth in the coming years. The changes in the approaches of regulatory agencies could significantly impact the development of therapeutics for use during pregnancy. However, limitations of the devices and molecular and biochemical assay shortfalls hinder the progress of the OOC field. This review describes available reproductive and pregnancy-related OOC platforms, and the current methodologies utilized to generate endpoint datasets (e.g., microscopic imaging, immunocytochemistry, real-time polymerase chain reaction, cytokine multiplex analysis). Microfluidic platform limitations, such as fewer number of cells or low supernatant volumes and restrictions regarding fabrication materials, are described. Novel approaches (e.g., spatial transcriptomics, imaging cytometry by time of flight, exosomes analysis using Exoview) to overcome these challenges are described. OOC platforms are primed to provide biologically relevant and clinically translational data that can revolutionize in-vitro physiological modeling, drug discovery, and toxicologic risk assessment. However, engineering adaptations to increase the throughput of devices (i.e., device arrays) and biological advancements to improve data throughput are both needed for these platforms to reach their full potential.National Institute of Child Health and Human DevelopmentJohn Sealy School of Medicine University Blvd.Institute of Reproductive Health National Institutes of Health University of the Philippines ManilaDivision of Basic Science and Translational Research Department of Obstetrics and Gynecology The University of Texas Medical Branch at GalvestonDepartment of Pathology Botucatu Medical School São Paulo State UniversityCollege of Medicine San Beda UniversityDepartment of Chemistry College of Science De La Salle University ManilaDepartment of Biomedical Engineering and Electrical and Computer Engineering Texas A&M University, College StationGynecologic Cancer Center of Excellence Gynecologic Surgery and Obstetrics Uniformed Services University of the Health SciencesWomen’s Health Integrated Research Center Women’s Service Line Inova Health SystemDepartment of Pathology Botucatu Medical School São Paulo State UniversityNational Institute of Child Health and Human Development: UG3TR003283 R01HD110400 R01HD100729-01S
Survival of Xanthomonas euvesicatoria pv. perforans in soil and weeds
No full textA mancha bacteriana, causada por Xanthomonas euvesicatoria pv. perforans (Xep), é uma das principais doenças do tomateiro no Brasil, podendo ocasionar perdas superiores a 50% da produção. Embora estratégias de manejo estejam estabelecidas, a bactéria pode sobreviver entre safras em diferentes nichos ecológicos, favorecendo a reemergência da doença. Este trabalho teve como objetivo avaliar a sobrevivência de isolados de Xep em diferentes tipos de solo e na filosfera e rizosfera de plantas daninhas comumente encontradas em áreas de cultivo de tomateiro. Foram conduzidos sete experimentos de solo e quatro com plantas daninhas. Os experimentos de solo utilizaram cinco tipos distintos e seis isolados bacterianos. Já os testes com plantas daninhas envolveram 14 espécies, com inoculação simultânea na parte aérea e na rizosfera. A sobrevivência bacteriana foi monitorada por plaqueamento seletivo por um período de até 70 dias. De maneira geral, a Xep apresentou baixa sobrevivência no solo, sendo detectada apenas até sete dias após a inoculação na maioria dos casos. No entanto, em condições específicas, um isolado sobreviveu por mais de 70 dias. Nas plantas daninhas, a Xep sobreviveu por até 49 dias na filosfera de algumas espécies, mesmo sem causar sintomas aparentes, enquanto a sobrevivência na rizosfera foi, em geral, inferior a 21 dias. Os resultados indicam que plantas daninhas podem atuar como reservatórios de inóculo entre ciclos de cultivo, sendo fundamentais no manejo da mancha bacteriana.Bacterial spot, caused by Xanthomonas euvesicatoria pv. perforans (Xep), is one of the main diseases affecting tomato crops in Brazil, with potential yield losses exceeding 50%. Although management strategies have been established, the bacterium may persist between cropping seasons in different ecological niches, contributing to disease reemergence. This study aimed to evaluate the survival of Xep isolates in different soil types and in the phyllosphere and rhizosphere of common weed species found in tomato cultivation areas. Seven soil experiments and four weed experiments were conducted. The soil trials involved five distinct soil types and six bacterial isolates, while the weed trials included 14 species, with simultaneous inoculation of aerial parts and rhizosphere. Bacterial survival was monitored for up to 70 days through selective media plating. Overall, Xep showed low survival in soil, being recovered only up to seven days after inoculation in most cases. However, under specific conditions, one isolate survived for over 70 days. On weeds, Xep survived up to 49 days in the phyllosphere of some species, even without visible symptoms, while rhizosphere survival was generally less than 21 days. These findings suggest that weeds can serve as important inoculum reservoirs between tomato cropping cycles and should be considered in integrated disease management strategies.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)2023/02555-
Italian immigrants, football clubs, and the city (1880–1930): Palestra Itália and Cotonifício Rodolfo Crespi in the urbanization of São Paulo
No full textEste trabalho tem como objetivo principal analisar o processo de expansão urbana da cidade de São Paulo, com um foco especial na imigração italiana e na criação de clubes de futebol como elementos-chave desse desenvolvimento. A relevância deste estudo reside na importância dos processos históricos e na consolidação da Geografia Cultural, especialmente ao utilizar o futebol — um componente significativo da cultura popular, porém ainda subexplorado nos estudos geográficos — como um ponto de partida para essa análise. Por meio da Geografia Urbana, busca-se compreender como a expansão da cidade de São Paulo se entrelaça com a chegada dos imigrantes italianos, que desempenharam um papel fundamental na formação da identidade cultural e social da cidade. Este trabalho utiliza como referência o relatório do Programa Institucional de Bolsas de Iniciação Científica (PIBIC), o que contribuiu para sua fundamentação teórica e metodológica. A pesquisa, de caráter documental e bibliográfico, foi realizada com base em acervos da Universidade Estadual Paulista (UNESP), da Universidade de São Paulo (USP) e da Universidade Estadual de Campinas (UNICAMP), permitindo uma abordagem sólida para compreender as dinâmicas urbanas e culturais. A análise dos dados demonstrou que a urbanização acelerada de São Paulo, impulsionada pela economia cafeeira e pela industrialização, teve participação ativa dos imigrantes italianos, tanto como força de trabalho nas indústrias quanto como agentes culturais. A fundação dos clubes Palestra Itália e Cotonifício Rodolfo Crespi, inseridos nos bairros operários e ligados diretamente ao capital e à identidade italiana, revelou-se estratégica na construção de redes de sociabilidade, identidade territorial e resistência cultural. Conclui-se que o futebol, ao mesmo tempo em que refletia e reforçava as estruturas sociais e econômicas do período, também funcionava como espaço de mediação simbólica, integração comunitária e apropriação urbana, sendo, portanto, um objeto legítimo de análise na Geografia Cultural e Urbana.This study aims to analyze the urban expansion process of the city of São Paulo, with a particular focus on Italian immigration and the creation of football clubs as key elements in this development. The relevance of this research lies in the importance of historical processes and the consolidation of Cultural Geography, especially by using football — a significant component of popular culture, yet still underexplored in geographic studies — as a starting point for this analysis. Through the lens of Urban Geography, the study seeks to understand how the expansion of São Paulo intertwines with the arrival of Italian immigrants, who played a fundamental role in shaping the city’s cultural and social identity. This work draws on the report from the Institutional Program of Scientific Initiation Scholarships (PIBIC), which contributed to its theoretical and methodological foundation. The research, documentary and bibliographic in nature, was conducted using collections from São Paulo State University (UNESP), the University of São Paulo (USP), and the University of Campinas (UNICAMP), enabling a robust approach to understanding urban and cultural dynamics. Data analysis showed that the accelerated urbanization of São Paulo, driven by the coffee economy and industrialization, involved active participation by Italian immigrants, both as labor in the industries and as cultural agents. The founding of the Palestra Itália and Cotonifício Rodolfo Crespi football clubs, located in working-class neighborhoods and directly linked to Italian capital and identity, proved strategic in the construction of sociability networks, territorial identity, and cultural resistance. It is concluded that football, while reflecting and reinforcing the social and economic structures of the time, also functioned as a space for symbolic mediation, community integration, and urban appropriation, thus representing a legitimate object of analysis in both Cultural and Urban Geography
The world impact of boron doped diamond electrodes and low-cost strategies for novel production systems for sustainable wastewater treatment
No full textConductive diamond films appeared as promising materials with exceptional electrochemical properties that allowed significant advances in scientific and engineering domains. Therefore, in this opinion, we have explored the world's impact of boron doped diamond electrodes regarding its use in wastewater and disinfection from the point of view of the published scientific communications, preparation methodologies and the commercialization of these materials by several companies in different countries. A brief discussion about the scientific centers and institutes that have dedicated efforts to investigate diamond electrochemistry and its applications, has been included. More specifically, an opinion about the improvements in the fabrication of novel BDD electrodes and the design and construction of small electrochemical devices with different BDD materials. Trends on electrochemical technologies, using home-built and commercial BDD electrodes in environmental applications, have been also explored. The most important low-cost strategies for novel production systems for sustainable wastewater treatment and disinfection have been summarized and described. Finally, some examples of the types and devices of use of BDD electrodes are presented.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Renewable Energies and Environmental Sustainability Research Group Institute of Chemistry Federal University of Rio Grande do Norte Campus Universitário, Av. Salgado Filho 3000, Lagoa Nova, Rio Grande do NorteNational Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT–DATREM) Institute of Chemistry UNESP, P.O. Box 355, SPSchool of Science and Technology Federal University of Rio Grande do Norte Campus Universitario, Av. Salgado Filho 3000, Lagoa NovaDepartment of Environmental Health Engineering School of Public Health Research Centre for Health Sciences Hamadan University of Medical SciencesNational Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT–DATREM) Institute of Chemistry UNESP, P.O. Box 355, SPFAPESP: 2019/13113-4CNPq: 408110/2022-8FAPESP: FAPESP 2014/50945-
Theoretical evaluation of xylanase separation produced by Escherichia coli through filtration and centrifugation processes using a flocculant
No full textEste trabalho avalia teoricamente os processos de clarificação e separação na produção de xilanase por Escherichia coli, com foco nas técnicas de filtração e centrifugação, utilizando o floculante quitosana. A xilanase, uma enzima que degrada xilana, é amplamente aplicada em indústrias como biocombustíveis, papel e celulose, alimentícia e de rações. A produção recombinante em Escherichia coli oferece vantagens como crescimento rápido e manipulação genética, mas enfrenta desafios na purificação devido a contaminantes celulares. Foram propostos testes de centrifugação (500, 1.000 e 10.000 G) e filtração (microfiltração de 0,45 μm e ultrafiltração de 30 kDa) com floculante para otimizar a clarificação do caldo fermentativo.This study theoretically evaluates the clarification and separation processes in the production of xylanase by Escherichia coli, focusing on filtration and centrifugation techniques, using different dosages of the flocculant chitosan. Xylanase, an enzyme that degrades xylan, is widely applied in industries such as biofuels, paper and pulp, food, and animal feed. Recombinant production in Escherichia coli offers advantages like rapid growth and genetic manipulation but faces challenges in purification due to cellular contaminants. Centrifugation tests (500, 1,000, and 10,000 G) and filtration (microfiltration at 0.45 μm and ultrafiltration at 30 kDa) with flocculant were proposed to optimize the clarification of the fermentation broth