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1.
Rev. cuba. med ; 62(4)dic. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1550882

RESUMO

Introducción: Varios miembros del Departamento de Investigaciones en Adicciones de la Universidad de Ciencias Médicas de La Habana participaron en el 2020 y 2021 como docentes, asesores y directores de tesis en dos programas de formación académica de estudiantes ecuatorianos: especialización en Medicina Familiar y Comunitaria y maestría en Psicología Clínica (mención en Salud Mental Comunitaria). Objetivo: Describir los resultados del estudio y las investigaciones concluidas en ambos programas de formación académica. Método: Se realizó un estudio descriptivo de corte transversal basado en el análisis de los 69 proyectos de investigación desarrollados. Para la descripción de los resultados se realizó el análisis de contenido del 20 % de las investigaciones. Resultados: El 63,8 % de los estudios fueron investigaciones biomédicas, y el 36,1 % fueron estudios psicosociales. En ambos casos, el contexto social en las comunidades fue de (84,7 %). Entre las investigaciones médicas predominaron las dirigidas al paciente con hipertensión arterial (39,1 %) centradas en la adherencia terapéutica (32,6 %). En los estudios psicológicos predominaron los dirigidos a niños y adolescentes (23,0 %) y a profesionales sanitarios (23,0 %) centradas en las afecciones mentales (19,2 %). Conclusiones: Los proyectos desarrollados concluyeron resultados satisfactorios, se describió con mayor sistematicidad el enfoque comunitario en las investigaciones biomédicas. Se abordaron contenidos relativos a la adherencia terapéutica y las afectaciones a la salud mental. El impacto de la COVID-19 fue valorado como generador de dificultades en niños y adolescentes, profesionales sanitarios y en la población.


Introduction: In 2020 and 2021, the Department of Research on Addiction of Havana University of Medical Sciences participated as teachers, advisors and thesis directors in two academic training programs for Ecuadorian students: specialization in Family and Community Medicine and master's degree in Clinical Psychology with a mention in Community Mental Health. Objective: To describe the results of the study and the research concluded in both academic training programs. Methods: A descriptive cross-sectional study was carried out based on the analysis of the sixty nine research projects established. The content analysis of 20% of the investigations was carried out to describe the results. Results: 63.8% of the studies were biomedical research and 36.1% were psychosocial studies. In both cases, communities was the social context (84.7%). Among the medical investigations, those aimed at the patient with hypertension (39.1%) focused on therapeutic adherence (32.6%) predominated. In the psychological studies, those intended at children and adolescents (23.0%) and health professionals (23.0%) focused on mental disorders (19.2%) prevailed. Conclusions: These projects yielded satisfactory results. The community approach in biomedical research was more systematically described. Contents related to therapeutic adherence and the effects on mental health were addressed. The impact of COVID-19 was assessed as generator of difficulties in children and adolescents, health professionals, and in the population.

2.
Biomater Adv ; 154: 213587, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37633007

RESUMO

In this work, Engineered Living Materials (ELMs), based on the combination of genetically-modified bacteria and mineral-reinforced organic matrices, and endowed with self-healing or regenerative properties and adaptation to specific biological environments were developed. Concretely, we produced ELMs combining human mesenchymal stem cells (hMSCs) and Lactococcus lactis (L. lactis), which was specifically programmed to deliver bone morphogenetic protein (BMP-2) upon external stimulation using nisin, into mineralized alginate matrices. The hybrid organic/inorganic matrix was built through a protocol, inspired by bone mineralization, in which alginate (Alg) assembly and apatite (HA) mineralization occurred simultaneously driven by calcium ions. Chemical composition, structure and reologhical properties of the hybrid 3D matrices were dedicately optimized prior the incorportation of the living entities. Then, the same protocol was reproduced in the presence of hMSC and engineered L. lactis that secrete BMP-2 resulting in 3D hybrid living hydrogels. hMSC viability and osteogenic differentiation in the absence and presence of the bacteria were evaluated by live/dead and quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence assays, respectively. Results demonstrate that these 3D engineered living material support osteogenic differentiation of hMSCs due to the synergistic effect between HA and the growth factors BMP-2 delivered by L. lactis.


Assuntos
Calcinose , Células-Tronco Mesenquimais , Humanos , Osteogênese/genética , Tecidos Suporte/química , Células-Tronco Mesenquimais/metabolismo , Alginatos , Diferenciação Celular , Calcinose/metabolismo
3.
Biomater Adv ; 154: 213595, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37639856

RESUMO

New strategies to develop drug-loaded nanocarriers with improved therapeutic efficacy are needed for cancer treatment. Herein we report a novel drug-delivery nanosystem comprising encapsulation of the chemotherapeutic drug docetaxel (DTX) and recombinant fusion of a small peptide inhibitor of Akt kinase within an elastin-like recombinamer (ELR) vehicle. This combined approach is also precisely targeted to colorectal cancer cells by means of a chemically conjugated DNA aptamer specific for the CD44 tumor marker. This 53 nm dual-approach nanosystem was found to selectively affect cell viability (2.5 % survival) and proliferation of colorectal cancer cells in vitro compared to endothelial cells (50 % survival), and to trigger both apoptosis- and necrosis-mediated cell death. Our findings also show that the nanohybrid particles remain stable under physiological conditions, trigger sustained drug release and possess an adequate pharmacokinetic profile after systemic intravenous administration. In vivo assays showed that these dual-approach nanohybrids significantly reduced the number of tumor polyps along the colorectal tract in a murine colorectal cancer model. Furthermore, systemic administration of advanced nanohybrids induced tissue recovery by improving the morphology of gastrointestinal crypts and the tissue architecture. Taken together, these findings indicate that our strategy of an advanced dual-approach nanosystem allows us to achieve successful controlled release of chemotherapeutics in cancer cells and may have a promising potential for colorectal cancer treatment.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Nanopartículas , Camundongos , Animais , Docetaxel/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Células Endoteliais , Portadores de Fármacos , Inibidores da Angiogênese , Neoplasias Colorretais/tratamento farmacológico
5.
Nutr. clín. diet. hosp ; 43(2): 61-67, May 1, 2023. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-219787

RESUMO

Introducción: La hipertensión arterial es el principalriesgo de sufrir enfermedad cardiovascular, muchos factoresimplicados entre ellos la edad, inactividad física, sexo, tabaquismo, alcohol, stress y obesidad.Objetivos: Identificar el efecto mediador del índice demasa corporal en la relación entre antecedentes personales ypresión arterial del personal de salud. Métodos: Estudio transversal, se obtuvo acceso a la fichamédica electrónica del departamento de medicina ocupacional. La muestra fue de 748 trabajadores de la salud Hospitalde Guayaquil. Se utilizó el modelo de mediación simple paraverificar si existía asociación entre los antecedentes personales de hipertensión arterial y la presión sanguínea, mediadapor el IMC, utilizando la macro PROCESS v. 4.1 y el programaSPSS (versión 26.0). Resultados: El IMC fue = 29,37 kg/m2 (sobrepeso).Losvarones presentaron mayor presión sistólica (124,42 mmHg) ydiastólica (76,85 mmHg) comparado con las mujeres (115,44mmHg y 71,92 mmHg respectivamente) (p<0,05). Solo en lasmujeres se encontró un efecto indirecto del IMC en la asociación de los antecedentes personales de hipertensión arterial(APH) y la presión tanto sistólica como diastólica (p<0,001).Conclusión: El antecedente personal de hipertensión arterial está asociado con el incremento de la presión de formadirecta (sea sistólica o diastólica). Además, el IMC es una variable mediadora que actúa en la asociación.(AU)


Introduction: High blood pressure is the main risk of cardiovascular disease, many factors involved including age,physical inactivity, sex, smoking, alcohol, stress and obesity.Objectives: To identify the mediating effect of the bodymass index in the relationship between personal history andblood pressure of health personnel. Methods: Cross-sectional study, access was obtained tothe electronic medical record of the occupational medicine department. The sample was 748 health workers Hospital deGuayaquil. The simple mediation model was used to verify ifthere was an association between personal history of arterialhypertension and blood pressure, mediated by BMI, using themacro PROCESS v. 4.1 and the SPSS program (version 26.0).Results: The BMI was x = 29,37 kg/m2 (overweight). Menpresented higher systolic (124,42 mmHg) and diastolic (76,85mmHg) pressure compared to women (115,44 mmHg and71,92 mmHg respectively) (p<0,05). Only in women was anindirect effect of BMI found in the association of personal history of arterial hypertension (APH) and both systolic and diastolic blood pressure (p<0,001).Conclusion: The personal history of arterial hypertensionis directly associated with the increase in pressure (either systolic or diastolic). In addition, the BMI is a mediating variablethat acts in the association.(AU)


Assuntos
Humanos , Sexo , Índice de Massa Corporal , Hipertensão , Pessoal de Saúde , Equador , Estudos Transversais
6.
Nat Commun ; 14(1): 2068, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37045815

RESUMO

The limited number of targetable tumor-specific antigens and the immunosuppressive nature of the microenvironment within solid malignancies represent major barriers to the success of chimeric antigen receptor (CAR)-T cell therapies. Here, using epithelial cell adhesion molecule (EpCAM) as a model antigen, we used alanine scanning of the complementarity-determining region to fine-tune CAR affinity. This allowed us to identify CARs that could spare primary epithelial cells while still effectively targeting EpCAMhigh tumors. Although affinity-tuned CARs showed suboptimal antitumor activity in vivo, we found that inducible secretion of interleukin-12 (IL-12), under the control of the NFAT promoter, can restore CAR activity to levels close to that of the parental CAR. This strategy was further validated with another affinity-tuned CAR specific for intercellular adhesion molecule-1 (ICAM-1). Only in affinity-tuned CAR-T cells was NFAT activity stringently controlled and restricted to tumors expressing the antigen of interest at high levels. Our study demonstrates the feasibility of specifically gearing CAR-T cells towards recognition of solid tumors by combining inducible IL-12 expression and affinity-tuned CAR.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Interleucina-12/genética , Molécula de Adesão da Célula Epitelial , Imunoterapia Adotiva , Neoplasias/genética , Neoplasias/terapia , Antígenos de Neoplasias/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Microambiente Tumoral
7.
Cell Biosci ; 13(1): 44, 2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36871010

RESUMO

In recent years, progress in nanotechnology provided new tools to treat cancer more effectively. Advances in biomaterials tailored for drug delivery have the potential to overcome the limited selectivity and side effects frequently associated with traditional therapeutic agents. While autophagy is pivotal in determining cell fate and adaptation to different challenges, and despite the fact that it is frequently dysregulated in cancer, antitumor therapeutic strategies leveraging on or targeting this process are scarce. This is due to many reasons, including the very contextual effects of autophagy in cancer, low bioavailability and non-targeted delivery of existing autophagy modulatory compounds. Conjugating the versatile characteristics of nanoparticles with autophagy modulators may render these drugs safer and more effective for cancer treatment. Here, we review current standing questions on the biology of autophagy in tumor progression, and precursory studies and the state-of-the-art in harnessing nanomaterials science to enhance the specificity and therapeutic potential of autophagy modulators.

8.
Environ Manage ; 71(2): 274-284, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36401632

RESUMO

Protected areas play an important role in biodiversity conservation and tourism. Significant efforts have been made to increase the amount of protected lands. A problem of increasing the amount of public protected areas is that governments and other institutions face difficulties in providing the necessary resources for effective management. Accordingly, managers must be as efficient as possible but the lack of comparative methods makes the evaluation of efficiency difficult. Using Data Envelopment Analysis, a non-stochastic and non-parametric approach, information from 29 protected areas in 5 countries was analyzed to compare management efficiency amongst them. The first result found is the level of management efficiency that each park has in comparison with the others parks. The other important result is a prediction of the changes in the outputs if there is a hypothetical budget change. These results allow the generation of information for decision making.


Assuntos
Conservação dos Recursos Naturais , Política Ambiental , Formulação de Políticas , Biodiversidade , Conservação dos Recursos Naturais/métodos , Humanos , Turismo
9.
Nutr. clín. diet. hosp ; 42(4): 43-51, Dic 4, 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-212963

RESUMO

En el Ecuador se optó por la implementación del etiquetadode advertencia debido a la gran oferta de alimentos procesa-dos endulzados con edulcorantes no calóricos (ENC) en res-puesta a la implementación de políticas públicas tanto parareducción del consumo azúcar, por lo que se considera muynecesario conocer los alimentos que ofrecen al consumidor,así como el nivel de dulzor clásico emplean uno o más ENC.Además, para captar la atención del cliente varios empaquespresentan frases como “cero azúcares”, “endulzado con este-via” o “libre de calorías” pese a tener una mezcla de edulco-rantes no calóricos y calóricos. El presente trabajo se desa-rrolló con el objetivo de crear una base de datos de alimentosprocesados para evidenciar los ENC más empleados. Se reco-lectó la información de 450 alimentos procesados que seagruparon en seis categorías. El 61% de los alimentos estu-diados empleó un solo ENC, 37% contaba con la combinaciónde dos ENC y el 2% empleó la mezcla tres ENC. El edulco-rante más empleado fue la sucralosa y la combinación másutilizada fue el aspartame y acesulfame K.(AU)


In Ecuador, the implementation of warning labeling waschosen due to the large supply of processed foods sweetenedwith non-caloric sweeteners (ENC) in response to the imple-mentation of public policies both to reduce sugar consump-tion, for which it is considers it very necessary to know thefoods offered to the consumer, as well as the level of classicsweets using one or more ENC. Additionally, to capture thecustomer’s attention, several packages present phrases suchas “zero sugar”, “sweetened with stevia” or “calorie free” de-spite having a mixture of non-caloric and caloric sweeteners.The present work was developed with the objective of creat-ing a database of processed foods to show the most usedENC. Information was collected from 450 processed foodsthat were grouped into six categories. 61% of the foods stud-ied used a single ENC, 37% had the combination of two ENCand 2% used the mixture of three ENC. The most used sweet-ener was sucralose and the most used combination was as-partame and acesulfame K.(AU)


Assuntos
Humanos , Adoçantes não Calóricos , Indústria de Processamento de Alimentos , Rotulagem de Alimentos , Edulcorantes , Equador , 52503 , Dietética
10.
Sci Rep ; 12(1): 19112, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352020

RESUMO

Regulatory T cells (Tregs) are essential to maintain self-tolerance and immune homeostasis but, as components of the tumor microenvironment (TME), are also a major barrier to effective cancer immunosurveillance and immunotherapy. FH535 and its derivative Y3 are two N-aryl-benzene-sulfonamides (NABs) that inhibit HCC cell proliferation and tumor progression. However, the impact of NABs on the immune cells in the TME is not yet known. Analyses of explanted livers from patients with hepatocellular carcinoma (HCC) showed that high levels of tumor-infiltrating Tregs were associated with poor tumor differentiation. These results lead us to investigate the immunomodulatory effects of NABs in regulatory and effector T cells. Exposure of primary human Tregs to NABs induced a rapid but temporary increase of cell expansion, a gradual disruption of suppressor activity, and concomitant bioenergetics and autophagic flux dysregulations. In contrast to Tregs, no gross effects were observed in effector T cells. Addition of Rapamycin prevented the functional decay of Tregs and restored their metabolic profile, suggesting that NAB effects require the integrity of the mTOR pathway. This study revealed the immunomodulatory properties of NABs with a preferential impact on Treg activity and provided novel insights into the anti-tumor potential of sulfonamides.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Linfócitos T Reguladores , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral , Sulfonamidas/farmacologia , Homeostase
11.
Methods Mol Biol ; 2465: 41-72, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35118615

RESUMO

In this chapter we describe two unconventional strategies for the formulation of new nanovaccines. Both strategies are based on obtaining chimeric genes that code for proteins in which the major antigens of the pathogens are fused to an elastin-like recombinamer (ELR) as carrier. ELRs are a family of synthetic protein biopolymers obtained using DNA recombinant techniques. The ELRs employed in the present chapter are block copolymers that are able to assemble, under controlled conditions, into nanoparticles similar to virus-like particles and to provoke an immune response. We describe the biosynthesis of ELRs genetically fused to an antigenic sequence from Mycobacterium tuberculosis and a simple procedure for obtaining stable nanoparticles displaying the antigen in the first strategy. The second approach describes the production of a DNA vaccine library consisting of plasmids codifying for major antigens from Rift Valley fever virus fused to different ELR-based block copolymer architectures.The procedures described can be adapted for the production of other chimeric DNA-protein vaccines based on protein polymer carriers.


Assuntos
Elastina , Nanopartículas , Animais , Elastina/genética , Epitopos , Polímeros , Engenharia de Proteínas
12.
ACS Appl Mater Interfaces ; 13(47): 55790-55805, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34788541

RESUMO

Pancreatic cancer is one of the deadliest cancers partly due to late diagnosis, poor drug delivery to the target site, and acquired resistance to therapy. Therefore, more effective therapies are urgently needed to improve the outcome of patients. In this work, we have tested self-assembling genetically engineered polymeric nanoparticles formed by elastin-like recombinamers (ELRs), carrying a small peptide inhibitor of the protein kinase Akt, in both PANC-1 and patient-derived pancreatic cancer cells (PDX models). Nanoparticle cell uptake was measured by flow cytometry, and subcellular localization was determined by confocal microscopy, which showed a lysosomal localization of these nanoparticles. Furthermore, metabolic activity and cell viability were significantly reduced after incubation with nanoparticles carrying the Akt inhibitor in a time- and dose-dependent fashion. Self-assembling 73 ± 3.2 nm size nanoparticles inhibited phosphorylation and consequent activation of Akt protein, blocked the NF-κB signaling pathway, and triggered caspase 3-mediated apoptosis. Furthermore, in vivo assays showed that ELR-based nanoparticles were suitable devices for drug delivery purposes with long circulating time and minimum toxicity. Hence, the use of these smart nanoparticles could lead to the development of more effective treatment options for pancreatic cancer based on the inhibition of Akt.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos/farmacologia , Polímeros/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lisossomos/química , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Tamanho da Partícula , Peptídeos/química , Polímeros/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Propriedades de Superfície
13.
SN Compr Clin Med ; 3(6): 1412-1415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33824942

RESUMO

Our case highlights SARS-CoV-2 and pembrolizumab as trigger of secondary hemophagocytic lymphohistiocytosis. Although it is a rare complication, it must be suspected in order to start specific treatment. In this context, intravenous immunoglobulins could be a therapeutic option.

14.
Int J Pharm ; 599: 120438, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33662472

RESUMO

Cancer has reached pandemic dimensions in the whole world. Although current medicine offers multiple treatment options against cancer, novel therapeutic strategies are needed due to the low specificity of chemotherapeutic drugs, undesired side effects and the presence of different incurable types of cancer. Among these new strategies, nanomedicine arises as an encouraging approach towards personalized medicine with high potential for present and future cancer patients. Therefore, nanomedicine aims to develop novel tools with wide potential in cancer treatment, imaging or even theranostic purposes. Even though numerous preclinical studies have been published with successful preliminary results, promising nanosystems have to face multiple obstacles before adoption in clinical practice as safe options for patients with cancer. In this MiniReview, we provide a short overview on the latest advances in current nanomedicine approaches, challenges and promising strategies towards more accurate cancer treatment.


Assuntos
Nanomedicina , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Medicina de Precisão , Nanomedicina Teranóstica
15.
JPEN J Parenter Enteral Nutr ; 45(3): 633-642, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32384172

RESUMO

BACKGROUND: Our objective was to assess in non-critically-ill adult inpatients receiving parenteral nutrition (PN) the risk of developing liver function test (LFT) alterations when receiving concomitant possibly hepatotoxic medications or others reported to improve LFTs during PN. METHODS: A multicenter retrospective analysis of prospectively collected data was performed on patients receiving PN. Two groups were recruited: group LALT (patients with any LFT alterations during PN), and group NOLALT (patients without such alterations). Exclusion criteria were previous sepsis, shock, renal failure, hyperglycemia, LFT alteration, or biliopancreatic surgical procedures. Medications were classified into 2 categories: medications reported to improve LFTs during PN (n = 8) and possibly hepatotoxic medications (n = 54), including a subgroup of possibly highly hepatotoxic medications (n = 30). RESULTS: The study included 200 patients, 136 (68.0%) in the LALT group. The groups differed in the number of patients requiring surgical intervention ≤7 days before PN (LALT, 94 [69.1%]; NOLALT, 29 [45.3%]; P < .002) and those receiving possibly hepatotoxic medications (LALT, 126 [92.6%]; NOLALT, 45 [70.3%]; P < .001). Variables in the final Cox regression model were possibly hepatotoxic medications, odds ratio (OR) 3.310 (1.678-6.530); surgical intervention prior to PN, OR 1.861 (1.277-2.711); baseline triglyceridemia, OR 1.005 (1.001-1.009); and creatinine, OR 1.861 (1.043-3.323). CONCLUSIONS: Patients who received PN and concomitantly possibly hepatotoxic medications had a 3-fold risk of developing LFT alterations. Medications reported to improve LFTs had no effect. The use of possibly hepatotoxic medications during PN was associated with LFT alterations.


Assuntos
Nutrição Parenteral Total , Nutrição Parenteral , Adulto , Estudos de Coortes , Humanos , Testes de Função Hepática , Nutrição Parenteral/efeitos adversos , Estudos Retrospectivos
16.
Pharmaceutics ; 12(11)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33228250

RESUMO

Biomaterials science is one of the most rapidly evolving fields in biomedicine. However, although novel biomaterials have achieved well-defined goals, such as the production of devices with improved biocompatibility and mechanical properties, their development could be more ambitious. Indeed, the integration of active targeting strategies has been shown to allow spatiotemporal control of cell-material interactions, thus leading to more specific and better-performing devices. This manuscript reviews recent advances that have led to enhanced biomaterials resulting from the use of natural structural macromolecules. In this regard, several structural macromolecules have been adapted or modified using biohybrid approaches for use in both regenerative medicine and therapeutic delivery. The integration of structural and functional features and aptamer targeting, although still incipient, has already shown its ability and wide-reaching potential. In this review, we discuss aptamer-functionalized hybrid protein-based or polymeric biomaterials derived from structural macromolecules, with a focus on bioresponsive/bioactive systems.

17.
Int J Biol Macromol ; 164: 1640-1648, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758602

RESUMO

One of the main goals in both tissue engineering and regenerative medicine is to design innovative synthetic scaffolds that can simulate and control the communication pathways between cells and the extracellular matrix (ECM). In this context, we describe herein the characterization of protein polymer, a recombinant elastin-like recombinamer (ELR) designed for developing tissue-engineered devices for use in vascular regeneration. This ELR is composed of an elastin-like backbone that contains a fibronectin domain, which provides specific, endothelial cell adhesion, and a protease target domain directed towards specific proteases involved in ECM remodeling. We also compare the specific response of endothelial and fibroblast cells to ELR scaffolds and show that cell adhesion and spreading on this ELR is significantly higher for endothelial cells than for fibroblasts. The reactivity of this polymer and its hydrogels to specific enzymatic degradation is demonstrated in vitro. As with natural elastin, enzymatic hydrolysis of the ELR produces elastin-derived peptides, or "matrikines", which, in turn, are potentially able to regulate important cell activities.


Assuntos
Elastina/química , Receptores de Superfície Celular/química , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis/química , Polímeros/química , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Tecidos Suporte/química
18.
Front Psychol ; 11: 1124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32595558

RESUMO

One of the purposes of education is to help pupils develop a responsible attitude, which is understood to be the capacity to vouch for their actions appropriately and in a way that fits social norms. Training of this type should be intentional, planned, and personalized, which will depend on how developed the individual's social responsibility is. This in turn is influenced by personal and family variables. This article provides an analysis of the interaction of some of those variables with the development of social responsibility in primary education pupils as the basis for the design of programs to promote personal and social responsibility tailored to the features of the pupils. To do this, the Social Responsibility Attitudes Scale was applied to 502 pupils taking grades 2 (8 years old), 4 (10 years old), and 6 (12 years old) of primary education. This scale measures the following factors: (a) obedient in family settings, (b) polite and accepting their mistakes, (c) trust in their parents, (d) responsibility in school setting, (e) friendly and willing to help, and (f) careful of the environment. By carrying out a multivariate analysis with the school grade, gender, family type (single, two-parent), and position among siblings (firstborn, only child, or not firstborn), it was concluded that attitudes related to prosociality start to be differentiated from grade 4 of primary education. It is in grade 6 that children become aware of their responsibility, and this is greater among that from two-parent families. However, no significant differences were found in the level of social responsibility with regard to gender or position among siblings.

19.
Mol Pharm ; 17(5): 1608-1620, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32233501

RESUMO

This work analyzes the immunogenicity of six genetically engineered constructs based on elastin-like recombinamers (ELRs) fused to the Gn glycoprotein from Rift Valley fever virus (RVFV). Upon transfection, all constructs showed no effect on cell viability. While fusion constructs including ELR blocks containing hydrophobic amino acids (alanine or isoleucine) did not increase the expression of viral Gn in eukaryotic cells, glutamic acid- or valine-rich fusion proteins showed enhanced expression levels compared with the constructs encoding the viral antigen alone. However, in vivo DNA plasmid immunization assays determined that the more hydrophobic constructs reduced viremia levels after RVFV challenge to a higher extent than glutamic- or valine-rich encoding plasmids and were better inducers of cellular immunity as judged by in vitro restimulation experiments. Although the Gn-ELR fusion constructs did not surpass the protective efficacy of a plasmid vaccine expressing nonfused Gn, our results warrant further experiments directed to take advantage of the immunomodulatory potential of ELR biomaterials for improving vaccines against infectious diseases.


Assuntos
Febre do Vale de Rift , Vírus da Febre do Vale do Rift , Doenças dos Ovinos , Vacinas de DNA , Vacinas Virais , Animais , Anticorpos Antivirais , Elastina/genética , Febre do Vale de Rift/prevenção & controle , Vírus da Febre do Vale do Rift/genética , Vírus da Febre do Vale do Rift/metabolismo , Ovinos , Doenças dos Ovinos/prevenção & controle , Valina , Vacinas Virais/genética
20.
Biomacromolecules ; 20(5): 1996-2007, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-30946582

RESUMO

This work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug-delivery system based on elastin-like block recombinamers. The DNA recombinant techniques allowed us to create this smart complex polymer containing bioactive sequences for internalization, lysosome activation under acidic pH, and blockage of cellular growth by a small peptide inhibitor. The recombinant polymer reversibly self-assembled when the temperature was increased above 15 °C into nanoparticles with a diameter of 72 nm and negative surface charge. Furthermore, smart nanoparticles were shown to enter in the cells via clathrin-dependent endocytosis and properly blocked phosphorylation and consequent activation of Akt kinase. This system provoked apoptosis-mediated cell death in breast and colorectal cancer cells, which possess higher expression levels of Akt, whereas noncancerous cells, such as endothelial cells, fibroblasts, and mesenchymal stem cells, were not affected. Hence, we conclude that the conformational complexity of this smart elastin-like recombinamer leads to achieving successful drug delivery in targeted cells and could be a promising approach as nanocarriers with bioactive peptides to modulate multiple cellular processes involved in different diseases.


Assuntos
Proliferação de Células , Endocitose , Nanopartículas/química , Polímeros Responsivos a Estímulos/química , Apoptose , Células CACO-2 , Células Cultivadas , Elastina/química , Elastômeros/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Lisossomos/metabolismo , Células MCF-7 , Nanopartículas/metabolismo , Peptídeos/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Eletricidade Estática , Temperatura
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