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1.
Int J Mol Sci ; 25(15)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39125655

RESUMO

Pancreatic cancer is a very aggressive disease with a dismal prognosis. The tumor microenvironment exerts immunosuppressive activities through the secretion of several cytokines, including interleukin (IL)-1. The IL-1/IL-1 receptor (IL-1R) axis is a key regulator in tumor-promoting T helper (Th)2- and Th17-type inflammation. Th2 cells are differentiated by dendritic cells endowed with Th2-polarizing capability by the thymic stromal lymphopoietin (TSLP) that is secreted by IL-1-activated cancer-associated fibroblasts (CAFs). Th17 cells are differentiated in the presence of IL-1 and other IL-1-regulated cytokines. In pancreatic cancer, the use of a recombinant IL-1R antagonist (IL1RA, anakinra, ANK) in in vitro and in vivo models has shown efficacy in targeting the IL-1/IL-1R pathway. In this study, we have developed sphingomyelin nanosystems (SNs) loaded with ANK (ANK-SNs) to compare their ability to inhibit Th2- and Th17-type inflammation with that of the free drug in vitro. We found that ANK-SNs inhibited TSLP and other pro-tumor cytokines released by CAFs at levels similar to ANK. Importantly, inhibition of IL-17 secretion by Th17 cells, but not of interferon-γ, was significantly higher, and at lower concentrations, with ANK-SNs compared to ANK. Collectively, the use of ANK-SNs might be beneficial in reducing the effective dose of the drug and its toxic effects.


Assuntos
Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1 , Neoplasias Pancreáticas , Esfingomielinas , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1/metabolismo , Esfingomielinas/metabolismo , Citocinas/metabolismo , Linhagem Celular Tumoral , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Células Th2/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Nanopartículas/química , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/efeitos dos fármacos
2.
Actual. nutr ; 25(2): 66-71, abr.jun.2024. ilus, graf, tab
Artigo em Espanhol | LILACS | ID: biblio-1562042

RESUMO

Introducción: La pérdida y el desperdicio de alimentos es una problemática mundial, compleja y que involucra a todos los actores de la cadena de suministro de alimentos. Debido a sus características ha sido incluida en la agenda 2030 del desarrollo sostenible. Objetivo: Conocer los motivos de desperdicio de alimentos del plato principal de los alumnos de sexto grado, en el servicio de alimentación de una escuela de la ciudad de Gualeguaychú. Materiales y métodos: Se desarrolló bajo la lógica cualitativa y tuvo un alcance exploratorio. La unidad de análisis fueron los alumnos de sexto grado. Se realizaron grupos focales y como complemento se implementó una guía de observación, fotografía y escala hedónica. Resultados: Los escolares prefieren las preparaciones de sus mamás y los motivos se relacionaron, principalmente, por las características organolépticas de las comidas. Preferían almorzar en el aula antes que en el comedor porque era un lugar más tranquilo. La aceptabilidad de los menús fue heterogénea y casi el 50% de los platos poseían algún tipo de desperdicio de alimentos, con predominio del desperdicio mayor al 25% de la porción servida. Conclusión: El estudio permitió conocer en mayor profundidad los motivos de desperdicio de alimentos. El rol del licenciado en Nutrición es importante para la gestión del servicio de alimentación escolar, para la planificación de menús de calidad nutricional y aceptados por los escolares. De esta manera, se contribuiría a reducir los desperdicios y mejorar la alimentación de los escolares


Food loss and waste is a global, complex problem that involves all actors in the food supply chain. Due to its characteristics, it has been included in the 2030 agenda for sustainable development. The objective of this study was to know the reasons for wasting food from the main dish of sixth grade students, in the food service of a school in the city of Gualeguaychú. It was developed under a qualitative approach. The unit of analysis was sixth grade students. Focus groups were held and, as a complement, the following were implemented: observation guide, photography and hedonic scale. The results showed that schoolchildren prefer their mothers' preparations and the reasons were mainly related to the organoleptic characteristics of the meals. They preferred to have lunch in the classroom rather than in the dining room because it was a quieter place. The acceptability of the menus was heterogeneous and almost 50% of the dishes had some type of food waste, most of the waste was greater than 25% of the portion served.In conclusion, the study allowed us to know in greater depth the reasons for food waste. The role of the Nutritionist is important for the management of the school food service, for the planning of menus of nutritional quality and appealing to schoolchildren; In this way, it would help to reduce waste and improve schoolchildren's nutrition


Assuntos
Alimentação Escolar , Instituições Acadêmicas , Perda e Desperdício de Alimentos
3.
Artigo em Inglês | MEDLINE | ID: mdl-38062286

RESUMO

While considerable efforts have been made to develop new therapies, progress in the treatment of pancreatic cancer has so far fallen short of patients' expectations. This is due in part to the lack of predictive in vitro models capable of accounting for the heterogeneity of this tumor and its low immunogenicity. To address this point, we have established and characterized a 3D spheroid model of pancreatic cancer composed of tumor cells, cancer-associated fibroblasts, and blood-derived monocytes. The fate of the latter has been followed from their recruitment into the tumor spheroid to their polarization into a tumor-associated macrophage (TAM)-like population, providing evidence for the formation of an immunosuppressive microenvironment.This 3D model well reproduced the multiple roles of TAMs and their influence on drug sensitivity and cell migration. Furthermore, we observed that lipid-based nanosystems consisting of sphingomyelin and vitamin E could affect the phenotype of macrophages, causing a reduction of characteristic markers of TAMs. Overall, this optimized triple coculture model gives a valuable tool that could find useful application for a more comprehensive understanding of TAM plasticity as well as for more predictive drug screening. This could increase the relevance of preclinical studies and help identify effective treatments.

4.
Int J Mol Sci ; 24(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37446374

RESUMO

The present study evaluates the ability of a novel plasma rich in growth factors (PRGF) membrane with improved optical properties to reduce oxidative stress in retinal pigment epithelial cells (ARPE-19 cells) exposed to blue light. PRGF was obtained from three healthy donors and divided into four main groups: (i) PRGF membrane (M-PRGF), (ii) PRGF supernatant (S-PRGF), (iii) platelet-poor plasma (PPP) membrane diluted 50% with S-PRGF (M-PPP 50%), and (iv) M-PPP 50% supernatant (S-PPP 50%). ARPE-19 cells were exposed to blue light and then incubated with the different PRGF-derived formulations or control for 24 and 48 h under blue light exposure. Mitochondrial and cell viability, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) and ZO-1 expression were evaluated. Mitochondrial viability and cell survival were significantly increased after treatment with the different PRGF-derived formulations. ROS synthesis and HO-1 expression were significantly reduced after cell treatment with any of the PRGF-derived formulations. Furthermore, the different PRGF-derived formulations significantly increased ZO-1 expression in ARPE-19 exposed to blue light. The new PRGF membrane with improved optical properties and its supernatant (M-PPP 50% and S-PPP 50%) protected and reversed blue light-induced oxidative stress in ARPE-19 cells at levels like those of a natural PRGF membrane and its supernatant.


Assuntos
Estresse Oxidativo , Epitélio Pigmentado da Retina , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células Epiteliais/metabolismo , Pigmentos da Retina/metabolismo
5.
Biomater Sci ; 11(12): 4397, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37255382

RESUMO

Correction for 'Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment' by Saínza Lores et al., Biomater. Sci., 2023, https://doi.org/10.1039/d2bm01456d.

6.
J Control Release ; 356: 702-713, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36931471

RESUMO

Intra-articular (IA) administration of drugs for the treatment of diseases such as rheumatoid arthritis, osteoarthritis and psoriatic arthritis is a common strategy; however, the rapid clearance from the synovial fluid restricts their effectivity due to the limited retention time. Drug Delivery Systems (DDS) are currently being developed to increase their joint retention time. This study compares the biodistribution and retention time of a senolytic peptide (PEP), with potential application in osteoarthritis disease, and this senolytic peptide encapsulated in a DDS based on a lipid nanoemulsion (PEPNE) by using positron emission tomography (PET) imaging. To this aim, the PEP was conjugated with a chelating agent (DFO) and radiolabeled with zirconium-89 (89Zr). Then, [89Zr]-PEP was encapsulated in a novel nanoemulsion formulation, composed by vitamin E, sphingomyelin, and a lipid-PEG. Afterward, healthy rats were administered with either the [89Zr]-PEP or the [89Zr]-PEP-NE via IA injection and underwent PET scans at 0.5-, 24-, 48-, 72-, 168-, 240- and 336 h post-injection. To assess the biodistribution of both radiotracers, several volume-of-interest were manually drawn in different organs of the rat body and the %ID/organ was calculated. The [89Zr]-PEP was successfully encapsulated in the NE and their physicochemical properties were minimally affected by the radiolabeling buffer. Adequate stability of both [89Zr]-PEP and [89Zr]-PEP-NE was found in synovial fluid over 72 h. Quantitative data from PET images revealed a significantly higher [89Zr]-PEP-NE retention in the injected knee than with [89Zr]-PEP in all follow-up PET scans. The [89Zr]-PEP %ID/organ values in the liver and kidney were significantly higher than those from [89Zr]-PEP-NE, which might indicate a faster elimination of the [89Zr]-PEP. Therefore, the study highlights the higher retention time on the target site of the [89Zr]-PEP-NE which may improve the therapeutic effects of the peptide. Thereby, the novel nanoemulsion formulation seems to be a successful DDS for IA injection. In addition, these results represent the first study that evaluates the distribution of a PET-guided DDS after its IA administration.


Assuntos
Desferroxamina , Senoterapia , Ratos , Animais , Distribuição Tecidual , Desferroxamina/química , Tomografia por Emissão de Pósitrons/métodos , Peptídeos , Lipídeos , Linhagem Celular Tumoral
7.
Biomater Sci ; 11(12): 4210-4225, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-36790445

RESUMO

Gene therapy has long been proposed for cancer treatment. However, the use of therapeutic nucleic acids presents several limitations such as enzymatic degradation, rapid clearance, and poor cellular uptake and efficiency. In this work we propose the use of putrescine, a precursor for higher polyamine biosynthesis for the preparation of cationic nanosystems for cancer gene therapy. We have formulated and characterized putrescine-sphingomyelin nanosystems (PSN) and studied their endocytic pathway and intracellular trafficking in cancer cells. After loading a plasmid DNA (pDNA) encoding the apoptotic Fas Ligand (FasL), we proved their therapeutic activity by measuring the cell death rate after treatment of MDA-MB-231 cells. We have also used xenografted zebrafish embryos as a first in vivo approach to demonstrate the efficacy of the proposed PSN-pDNA formulation in a more complex model. Finally, intratumoral and intraperitoneal administration to mice-bearing MDA-MB-231 xenografts resulted in a significant decrease in tumour cell growth, highlighting the potential of the developed gene therapy nanoformulation for the treatment of triple negative breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Camundongos , Animais , Feminino , Putrescina , Peixe-Zebra , Ciclo Celular , Morte Celular , Linhagem Celular Tumoral
8.
Front Pharmacol ; 13: 1007018, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386231

RESUMO

Gene therapy is a promising therapeutic approach that has experienced significant groth in recent decades, with gene nanomedicines reaching the clinics. However, it is still necessary to continue developing novel vectors able to carry, protect, and release the nucleic acids into the target cells, to respond to the widespread demand for new gene therapies to address current unmet clinical needs. We propose here the use of zebrafish embryos as an in vivo platform to evaluate the potential of newly developed nanosystems for gene therapy applications in cancer treatment. Zebrafish embryos have several advantages such as low maintenance costs, transparency, robustness, and a high homology with the human genome. In this work, a new type of putrescine-sphingomyelin nanosystems (PSN), specifically designed for cancer gene therapy applications, was successfully characterized and demonstrated its potential for delivery of plasmid DNA (pDNA) and miRNA (miR). On one hand, we were able to validate a regulatory effect of the PSN/miR on gene expression after injection in embryos of 0 hpf. Additionally, experiments proved the potential of the model to study the transport of the associated nucleic acids (pDNA and miR) upon incubation in zebrafish water. The biodistribution of PSN/pDNA and PSN/miR in vivo was also assessed after microinjection into the zebrafish vasculature, demonstrating that the nucleic acids remained associated with the PSN in an in vivo environment, and could successfully reach disseminated cancer cells in zebrafish xenografts. Altogether, these results demonstrate the potential of zebrafish as an in vivo model to evaluate nanotechnology-based gene therapies for cancer treatment, as well as the capacity of the developed versatile PSN formulation for gene therapy applications.

9.
ACS Nano ; 16(10): 16292-16313, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-35916497

RESUMO

Severe hemorrhage associated with trauma, surgery, and congenital or drug-induced coagulopathies can be life-threatening and requires rapid hemostatic management via topical, intracavitary, or intravenous routes. For injuries that are not easily accessible externally, intravenous hemostatic approaches are needed. The clinical gold standard for this is transfusion of blood products, but due to donor dependence, specialized storage requirements, high risk of contamination, and short shelf life, blood product use faces significant challenges. Consequently, recent research efforts are being focused on designing biosynthetic intravenous hemostats, using intravenous nanoparticles and polymer systems. Here we report on the design and evaluation of thrombin-loaded injury-site-targeted lipid nanoparticles (t-TLNPs) that can specifically localize at an injury site via platelet-mimetic anchorage to the von Willebrand factor (vWF) and collagen and directly release thrombin via diffusion and phospholipase-triggered particle destabilization, which can locally augment fibrin generation from fibrinogen for hemostatic action. We evaluated t-TLNPs in vitro in human blood and plasma, where hemostatic defects were created by platelet depletion and anticoagulation. Spectrophotometric studies of fibrin generation, rotational thromboelastometry (ROTEM)-based studies of clot viscoelasticity, and BioFlux-based real-time imaging of fibrin generation under simulated vascular flow conditions confirmed that t-TLNPs can restore fibrin in hemostatic dysfunction settings. Finally, the in vivo feasibility of t-TLNPs was tested by prophylactic administration in a tail-clip model and emergency administration in a liver-laceration model in mice with induced hemostatic defects. Treatment with t-TLNPs was able to significantly reduce bleeding in both models. Our studies demonstrate an intravenous nanomedicine approach for injury-site-targeted direct delivery of thrombin to augment hemostasis.


Assuntos
Hemostáticos , Trombina , Humanos , Camundongos , Animais , Fator de von Willebrand , Nanomedicina , Hemostasia , Plaquetas , Fibrina , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Fibrinogênio , Polímeros , Anticoagulantes
10.
Cancers (Basel) ; 14(9)2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35565373

RESUMO

Cancer causes millions of deaths each year and thus urgently requires the development of new therapeutic strategies. Nanotechnology-based anticancer therapies are a promising approach, with several formulations already approved and in clinical use. The evaluation of these therapies requires efficient in vivo models to study their behavior and interaction with cancer cells, and to optimize their properties to ensure maximum efficacy and safety. In this way, zebrafish is an important candidate due to its high homology with the human genoma, its large offspring, and the ease in developing specific cancer models. The role of zebrafish as a model for anticancer therapy studies has been highly evidenced, allowing researchers not only to perform drug screenings but also to evaluate novel therapies such as immunotherapies and nanotherapies. Beyond that, zebrafish can be used as an "avatar" model for performing patient-derived xenografts for personalized medicine. These characteristics place zebrafish in an attractive position as a role model for evaluating novel therapies for cancer treatment, such as nanomedicine.

11.
Animals (Basel) ; 12(6)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35327078

RESUMO

Echinococcosis is a neglected zoonosis that uses dogs and sheep as its main hosts in Chile. The Eg95 vaccine against sheep infection has been included in some control programs. Here, we assess the efficacy of the vaccination program in the hyperendemic Alto Biobío commune after 3 years of execution. Fisher's test and generalized linear models were used in the assessment. The program tried to offer a first dose at 2 months of age, a booster 1 month later, and yearly vaccination. Given logistic difficulties, important delays in vaccination occurred, and most animals did not receive the first booster. Dog deworming was not included in the program. Likely due to the aforementioned factors, the overall frequency of infection was not lower, but the proportion of large (>5 mm) cysts and fertile cysts was smaller after the program. The frequency of infection and/or the number of cysts were lower when the age at first dose was younger and the first booster was administered 1 month after the first dose. The results suggest that vaccination affects both cyst development after the larvae reach the target organs, as well as the development of the protoscolex once the cysts start developing.

12.
Int J Pharm ; 617: 121618, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35219823

RESUMO

Senescent cells accumulation can contribute to the development of several age-related diseases, including cancer. Targeting and eliminating senescence cells, would allow the development of new therapeutic approaches for the treatment of different diseases. The 4N1Ks peptide, a 10 amino acid peptide derived from TSP1 protein, combines both features by targeting the CD47 receptor present in the surface of senescent cells and demonstrating senolytic activity, thereby representing a new strategy to take into account. Nonetheless, peptide drugs are known for their biopharmaceutical issues, such as low short half-life and tendency to aggregate, which reduces their bioavailability and limits their therapeutic potential. In order to overcome this problem, herein we propose the use of biodegradable and biocompatible sphingomyelin nanosystems (SNs), decorated with this peptide for the targeting of senescent cells. In order to efficiently associate the 4N1Ks peptide to the nanosystems while exposing it on their surface for an effective targeting of senescent cells, the 4N1Ks peptide was chemically conjugated to a PEGylated hydrophobic chain. The resulting SNs-4N1Ks (SNs-Ks), were extensively characterized for their physicochemical properties, by dynamic light scattering, multiple-angle dynamic light scattering, nanoparticle tracking analysis and atomic force microscopy. The SNs-Ks demonstrated suitable features in terms of size (∼100 nm), association efficiency (87.2 ± 6.9%) and stability in different biorelevant media. Cell toxicity experiments in MCF7 cancer cells indicated an improved cytotoxic effect of SNs-Ks, decreasing cancer cells capacity to form colonies, with respect to free peptide, and an improved hemocompatibility. Lastly, senescence escape preliminary experiments demonstrated the improvement of SNs-Ks senolytic activity of in chemotherapy-induced senescence model of breast cancer cells. Therefore, these results demonstrate for the first time the potential of the combination of SNs with 4N1Ks peptide for the development of innovative senolytic therapies to battle cancer.


Assuntos
Antineoplásicos , Trombospondina 1 , Antineoplásicos/química , Senescência Celular , Peptídeos/farmacologia , Esfingomielinas/farmacologia , Trombospondina 1/farmacologia
13.
Int J Pharm ; 617: 121577, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35167901

RESUMO

Sphingomyelin nanosystems have already shown to be promising carriers for efficient delivery of anticancer drugs. For further application in the treatment of pancreatic tumor, the investigation on relevant in vitro models able to reproduce its physio-pathological complexity is mandatory. Accordingly, a 3D heterotype spheroid model of pancreatic tumor has been herein constructed to investigate the potential of bare and polyethylene glycol-modified lipid nanosystems in terms of their ability to penetrate the tumor mass and deliver drugs. Regardless of their surface properties, the lipid nanosystems successfully diffused through the spheroid without inducing toxicity, showing a clear safety profile. Loading of the bare nanosystems with a lipid prodrug of gemcitabine was used to evaluate their therapeutic potential. While the nanosystems were more effective than the free drug on 2D cell monocultures, this advantage, despite their efficient penetration capacity, was lost in the 3D tumor model. The latter, being able to mimic the tumor and its microenvironment, was capable to provide a more realistic information on the cell sensitivity to treatments. These results highlight the importance of using appropriate 3D tumor models as tools for proper in vitro evaluation of nanomedicine efficacy and their timely optimisation, so as to identify the best candidates for later in vivo evaluation.


Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Nanomedicina/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Esferoides Celulares , Esfingomielinas/farmacologia , Microambiente Tumoral
14.
Pharmaceutics ; 14(2)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35214191

RESUMO

The year 2020 was a turning point in the way society perceives science. Messenger RNA (mRNA) technology finally showed and shared its potential, starting a new era in medicine. However, there is no doubt that commercialization of these vaccines would not have been possible without nanotechnology, which has finally answered the long-term question of how to deliver mRNA in vivo. The aim of this review is to showcase the importance of this scientific milestone for the development of additional mRNA therapeutics. Firstly, we provide a full description of the marketed vaccine formulations and disclose LNPs' pharmaceutical properties, including composition, structure, and manufacturing considerations Additionally, we review different types of lipid-based delivery technologies currently in preclinical and clinical development, namely lipoplexes and cationic nanoemulsions. Finally, we highlight the most promising clinical applications of mRNA in different fields such as vaccinology, immuno-oncology, gene therapy for rare genetic diseases and gene editing using CRISPR Cas9.

15.
Pharmaceutics ; 13(9)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34575588

RESUMO

Long non-coding RNAs (lncRNAs) are an emerging group of RNAs with a crucial role in cancer pathogenesis. In gastrointestinal cancers, TP53 target 1 (TP53TG1) is an epigenetically regulated lncRNA that represents a promising therapeutic target due to its tumor suppressor properties regulating the p53-mediated DNA damage and the intracellular localization of the oncogenic YBX1 protein. However, to translate this finding into the clinic as a gene therapy, it is important to develop effective carriers able to deliver exogenous lncRNAs to the targeted cancer cells. Here, we propose the use of biocompatible sphingomyelin nanosystems comprising DOTAP (DSNs) to carry and deliver a plasmid vector encoding for TP53TG1 (pc(TP53TG1)-DSNs) to a colorectal cancer cell line (HCT-116). DSNs presented a high association capacity and convenient physicochemical properties. In addition, pc(TP53TG1)-DSNs showed anti-tumor activities in vitro, specifically a decrease in the proliferation rate, a diminished colony-forming capacity, and hampered migration and invasiveness of the treated cancer cells. Consequently, the proposed strategy displays a high potential as a therapeutic approach for colorectal cancer.

16.
Sci Rep ; 11(1): 17213, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446776

RESUMO

Colorectal cancer is the third most frequently diagnosed cancer malignancy and the second leading cause of cancer-related deaths worldwide. Therefore, it is of utmost importance to provide new therapeutic options that can improve survival. Sphingomyelin nanosystems (SNs) are a promising type of nanocarriers with potential for association of different types of drugs and, thus, for the development of combination treatments. In this work we propose the chemical modification of uroguanylin, a natural ligand for the Guanylyl Cyclase (GCC) receptor, expressed in metastatic colorectal cancer tumors, to favour its anchoring to SNs (UroGm-SNs). The anti-cancer drug etoposide (Etp) was additionally encapsulated for the development of a combination strategy (UroGm-Etp-SNs). Results from in vitro studies showed that UroGm-Etp-SNs can interact with colorectal cancer cells that express the GCC receptor and mediate an antiproliferative response, which is more remarkable for the drugs in combination. The potential of UroGm-Etp-SNs to treat metastatic colorectal cancer cells was complemented with an in vivo experiment in a xenograft mice model.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Etoposídeo/administração & dosagem , Nanopartículas/química , Peptídeos Natriuréticos/química , Esfingomielinas/química , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Etoposídeo/química , Etoposídeo/farmacologia , Feminino , Humanos , Camundongos Endogâmicos , Camundongos Nus , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Peptídeos Natriuréticos/metabolismo , Metástase Neoplásica , Tamanho da Partícula , Receptores Acoplados a Guanilato Ciclase/metabolismo , Carga Tumoral/efeitos dos fármacos
17.
Sci Rep ; 11(1): 9873, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972572

RESUMO

Triple negative breast cancer (TNBC) is known for being very aggressive, heterogeneous and highly metastatic. The standard of care treatment is still chemotherapy, with adjacent toxicity and low efficacy, highlighting the need for alternative and more effective therapeutic strategies. Edelfosine, an alkyl-lysophospholipid, has proved to be a promising therapy for several cancer types, upon delivery in lipid nanoparticles. Therefore, the objective of this work was to explore the potential of edelfosine for the treatment of TNBC. Edelfosine nanoemulsions (ET-NEs) composed by edelfosine, Miglyol 812 and phosphatidylcholine as excipients, due to their good safety profile, presented an average size of about 120 nm and a neutral zeta potential, and were stable in biorelevant media. The ability of ET-NEs to interrupt tumor growth in TNBC was demonstrated both in vitro, using a highly aggressive and invasive TNBC cell line, and in vivo, using zebrafish embryos. Importantly, ET-NEs were able to penetrate through the skin barrier of MDA-MB 231 xenografted zebrafish embryos, into the yolk sac, leading to an effective decrease of highly aggressive and invasive tumoral cells' proliferation. Altogether the results demonstrate the potential of ET-NEs for the development of new therapeutic approaches for TNBC.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas/administração & dosagem , Éteres Fosfolipídicos/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Administração Cutânea , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos/métodos , Emulsões , Excipientes/química , Feminino , Humanos , Nanopartículas/química , Permeabilidade , Fosfatidilcolinas/química , Éteres Fosfolipídicos/farmacocinética , Pele/metabolismo , Triglicerídeos/química , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
18.
Rev. bras. parasitol. vet ; 30(1): e024020, 2021. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1288686

RESUMO

Abstract Myiopsitta monachus is an invasive psittacine with wide distribution due to the pet trade. Its large communal nests and synanthropic nature contribute to its successful colonization of cities, from where it seems to be expanding in range and numbers. This is relevant with regard to pathogens that invasive species may harbor, especially when host populations thrive. We aimed to identify an abundant mite found in invasive monk parakeet chicks that had been collected in Santiago during 2017 and 2018. Through morphological and molecular identification of the 18S ribosomal RNA gene, we confirmed the presence of Ornithonyssus bursa. This was the first report of this mite in Chile. This mite is common in native and invasive monk parakeet populations and may affect other birds, including domestic fowl. Further, this mite bites people and can be a potential vector of pathogens such as bacteria or viruses. We conclude that this parasite was likely introduced with the parakeet and discuss possible ecological, health and economic consequences of this new potential pest.


Resumo Myiopsitta monachus é um psitacídeo invasor amplamente distribuído devido ao tráfico de animais selvagens. Os grandes ninhos comunitários construídos e sua condição de espécies sinantrópicas contribuem para a colonização bem-sucedida das cidades, onde parece estar expandindo sua distribuição e número de indivíduos. Isso é relevante, quando se trata de patógenos que os invasores podem abrigar, especialmente quando as populações hospedeiras prosperam. O objetivo deste trabalho foi identificar um ácaro abundante, encontrado em filhotes de periquitos-monge introduzidos em Santiago, Chile, coletados durante 2017 e 2018. Por meio da identificação morfológica e molecular do gene do RNA ribossômico 18S, foi confirmada a presença de Ornithonyssus bursa, sendo o primeiro registro para o Chile. Esse ácaro é comum em populações nativas e introduzidas de periquitos-monge e pode afetar outras aves, incluindo aves domésticas. Além disso, esse ácaro pode picar pessoas e pode ser um potencial vetor de patógenos, como bactérias ou vírus. Conclui-se que esse parasita provavelmente foi introduzido com o periquito e foram discutidas as possíveis consequências ecológicas de saúde e econômicas dessa nova praga em potencial.


Assuntos
Animais , Papagaios , Infestações por Ácaros/veterinária , Ácaros , Periquitos , Chile , Cidades
20.
Int J Mol Sci ; 21(20)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050198

RESUMO

PURPOSE: The purpose of this study was to examine the effect of plasma rich in growth factors (PRGFs) under blue light conditions in an in vivo model of retinal degeneration. METHODS: Male Wistar rats were exposed to dark/blue light conditions for 9 days. On day 7, right eyes were injected with saline and left eyes with PRGF. Electroretinography (ERG) and intraocular pressure (IoP) measurements were performed before and after the experiment. After sacrifice, retinal samples were collected. Hematoxylin and eosin staining was performed to analyze the structure of retinal sections. Immunofluorescence for brain-specific homeobox/POU domain protein 3A (Brn3a), choline acetyltransferase (ChAT), rhodopsin, heme oxygenase-1 (HO-1), and glial fibrillary acidic protein (GFAP) was performed to study the retinal conditions. RESULTS: Retinal signaling measured by ERG was reduced by blue light and recovered with PRGF; however, IoP measurements did not show significant differences among treatments. Blue light reduced the expression for Brn3a, ChAT, and rhodopsin. Treatment with PRGF showed a recovery in their expressions. HO-1 and GFAP results showed that blue light increased their expression but the use of PRGF reduced the effect of light. CONCLUSIONS: Blue light causes retinal degeneration. PRGF mitigated the injury, restoring the functionality of these cells and maintaining the tissue integrity.


Assuntos
Biomarcadores , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Degeneração Retiniana/sangue , Degeneração Retiniana/etiologia , Animais , Biópsia , Sobrevivência Celular , Eletrorretinografia , Imunofluorescência , Imuno-Histoquímica , Pressão Intraocular , Luz , Ratos , Degeneração Retiniana/diagnóstico , Transdução de Sinais
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