Long-term release of bioactive interferon-alpha from PLGA-chitosan microparticles: in vitro and in vivo studies.

Effective cytokine treatments often require high- and multiple-dose due to the short half-life of these molecules. Here, porcine interferon-alpha (IFNα) is encapsulated in PLGA-chitosan microparticles (IFNα-MPs) to accomplish both slow drug release and drug protection from degradation. A procedure that combines emulsion and spray-drying techniques yielded almost spherical microspheres with an average diameter of 3.00 ± 1.50 µm. SEM, Microtrac, and Z-potential analyses of three IFNα-MP batches showed similar results, indicating the process is reproducible. These studies supported molecular evidence obtained in FTIR analysis, which indicated a compact structure of IFNα-MPs. Consistently, IFNα release kinetics assessed in vitro followed a zero-order behavior typical of sustained release from a polymeric matrix. This study showed that IFNα-MPs released bioactive molecules for at least 15 days, achieving IFNα protection. In addition, pigs treated with IFNα-MPs exhibited overexpression of IFNα-stimulated genes 16 days after treatment. Instead, the expression levels of these genes decreased after day 4th in pigs treated with non-encapsulated IFNα. In vitro and in vivo experiments demonstrated that the formulation improved the prophylactic and therapeutic potential of IFNα, accomplishing molecule protection and long-term release for at least two weeks. The procedure used to obtain IFNα-MPs is reproducible, scalable, and suitable for encapsulating other drugs.

Use of scaffolds and regenerative materials for the treatment of immature necrotic permanent teeth with periapical lesion: Umbrella review.

BACKGROUND: Current treatment of immature necrotic permanent teeth with a periapical lesion is regenerative endodontics, which is based on tissue engineering under the triade of stem cells, scaffolds and bioactive molecules. OBJECTIVES: This Umbrella Review was aimed to evaluate the success of scaffold and regenerative materials used for the treatment of these teeth, in terms of apical closure, tooth length increase, widening of root canal walls, tissue vitality and periapical lesion repair. METHODS: An extensive literature research was carried out in the Medline, ISI Web of Science, and Scopus databases for relevant systematic reviews matching the keyword search strategy. Based on inclusion and exclusion criteria, reviewers independently rated the quality of each study to determine their level of evidence. Methodological quality assessment of each article was obtained using A Measurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool, and risk of bias was assessed with the Risk of Bias in Systematic Reviews (ROBIS) tool. RESULTS: After removing duplicates, 155 articles were found; from which 133 were excluded for being non-relevant and 15 other due to exclusion criteria. One more was discarded after methodological quality evaluation, for a total of six articles remaining. The most common scaffold used was the blood clot, others used were poly lactic-co-glycolic acid and platelet-rich fibrin matrix. The most common regeneration material used was Mineral Trioxide Aggregate (MTA), followed by Biodentine. An increase in tooth length and widening of root canal walls were reported in all selected studies with different proportions, as well as periapical lesion repair. ROBIS analysis showed that only one article had low bias, two were classified as unclear bias, while the remaining three had high risk of bias. DISCUSSION: An exhaustive literature search was carried out applying language filters, high-quality indexed journals, year of publication, which ensures the best quality articles were included. Blood clot was the most used scaffold as is the most easy to place inside the canal and does not require to extract blood from the patient. The use of MTA and Biodentine as sealing materials has been associated with thickening of canal walls, apical closure and reduced signs and symptoms of apical periodontitis. However, most of the included reviews assessed were case reports and only in a few of them were clinical trials included. There is also a lack of risk of bias analysis in most reviews. CONCLUSION: The blood clot is the most common scaffold used for inducing regeneration during the treatment of immature necrotic teeth. Tooth length increase and widening of root canal walls are the most common criteria used in the studies as success indicators. MTA and Biodentine did not show differences in the results analysed. Quality assessment and bias risk evaluation showed that it is necessary to design better studies with rigorous methodology to recommend a trustable and predictable protocol for the treatment of immature necrotic permanent teeth with periapical lesions. REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42021248404.

Expression and characterization of a novel single-chain anti-vascular endothelial growth factor antibody in the goat milk.

Vascular endothelial growth factor (VEGF) has essential functions in angiogenesis, endothelial cell proliferation, migration, and tumor invasion. Different approaches have been developed to suppress tumor angiogenesis, which is considered a hallmark of cancer. Anti-VEGF monoclonal antibodies constitute an important strategy for cancer immunotherapy, which has been produced on several platforms. In this study, a novel single-chain anti-VEGF monoclonal antibody (scVEGFmAb) was produced in the goat mammary gland by adenoviral transduction. scVEGFmAb was purified by affinity chromatography. N-glycans were analyzed by exoglycosidase digestion and hydrophilic interaction ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry. The biological activity of scVEGFmAb was assessed by scratch and mouse aortic ring assays. scVEGFmAb was produced at 0.61 g/L in the goat milk, and its purification rendered 95 % purity. N-glycans attached to scVEGFmAb backbone were mainly neutral biantennary core fucosylated with Galß1,4GlcNAc motif, and charged structures were capped with Neu5Ac and Neu5Gc. The chimeric molecule significantly prevented cell migration and suppressed microvessel sprouting. These results demonstrated for the first time the feasibility of producing an anti-VEGF therapeutic antibody in the milk of non-transgenic goats with the potential to counteract tumor angiogenesis.

A Heterologous Viral Protein Scaffold for Chimeric Antigen Design: An Example PCV2 Virus Vaccine Candidate.

Recombinant vaccines have low-cost manufacturing, regulatory requirements, and reduced side effects compared to attenuated or inactivated vaccines. In the porcine industry, post-weaning multisystemic disease syndrome generates economic losses, characterized by progressive weight loss and weakness in piglets, and it is caused by porcine circovirus type 2 (PCV2). We designed a chimeric antigen (Qm1) to assemble the main exposed epitopes of the Cap-PCV2 protein on the capsid protein of the tobacco necrosis virus (TNV). This design was based on the Cap-N-terminal of an isolated PCV2 virus obtained in Chile. The virus was characterized, and the sequence was clustered within the PCV2 genotype b clade. This chimeric protein was expressed as inclusion bodies in both monomeric and multimeric forms, suggesting a high-molecular-weight aggregate formation. Pigs immunized with Qm1 elicited a strong and specific antibody response, which reduced the viral loads after the PCV2 challenge. In conclusion, the implemented design allowed for the generation of an effective vaccine candidate. Our proposal could be used to express the domains or fragments of antigenic proteins, whose structural complexity does not allow for low-cost production in Escherichia coli. Hence, other antigen domains could be integrated into the TNV backbone for suitable antigenicity and immunogenicity. This work represents new biotechnological strategies, with a reduction in the costs associated with vaccine development.

A proposta de desenvolvimento rural e de educação da fao nos anos 1950 e na atualidade: forjando consensos como disfarce social / Fao's rural development and education proposals in the 1950's and today: forging consensus as social disguise

RESUMO: A Organização das Nações Unidas para Alimentação e Agricultura - FAO, agência da ONU, atua com expressividade nos programas de governo de combate à fome e de desenvolvimento rural no Brasil, bem como em países da América Latina, Caribe e África. Neste artigo apresentamos como objeto de estudo a relação entre a proposta de desenvolvimento rural da FAO e os princípios educativos defendidos por esta agência nos anos 1950 e a partir de 2005.O estudo foi realizado por meio de fontes secundárias e primárias, cuja síntese das conclusões aponta que como nos anos 1950, e coerentemente com a metodologia da FAO de constituição de consensos sociais em torno das propostas de desenvolvimento rural e educativa, atualmente são lançadas bandeiras de lutas que aglutinam setores sociais antagônicos em torno de uma proposta que promove a inserção subordinada das populações do campo à lógica do mercado.

ABSTRACT: The Food and Agriculture Organization - FAO, a UN Agency - acts with expressiveness in hunger relief and rural development programs in Brazil, as well as in other countries in Latin America, the Caribbean and Africa. In this article we analyze the relationship between FAO's rural development proposal and educational principles advocated by the agency during the 1950's and also since 2005. The study was conducted through secondary and primary sources. Summarizing the conclusions, today, as in the 1950s, the organization supports campaigns that gather antagonistic social sectors around projects that promote insertion of countryside population subordinated to market's logic, a strategy consistent with FAO's methodology for the establishment of social consensus for rural and educational development.

Carga de cáncer del departamento de Nariño ysubregiones, Colombia, 2010 / The burden of cancer in the department of Nariño and its subregions, Colombia, 2010

Objetivo: medir la carga de cáncer a partir del indicadorAños de Vida Saludables Perdidos (avisa) en el Departamentode Nariño y subregiones. Metodología: mediante el usode avisa, identificar la carga de cáncer en el departamentode Nariño, 2010. Resultados: Los avisa por cáncer en elDepartamento de Nariño destacan la emergencia de lostumores de estómago, cuello uterino, mama, próstata, colony recto, tráquea/bronquios/pulmón, benignos, las leucemiasy linfomas, asimismo una suma importante de años de vidaperdidos por muerte prematura y de predominio en mujeres.Conclusiones: este es el primer estudio de carga por cáncerde un departamento en Colombia usando una metodologíaestandarizada, que contribuye al Plan de Salud Departamentalde Nariño, Colombia 2013-2015 y al sistema de indicadoresdel Plan Decenal para el Control del Cáncer. Los cánceres,luego de las enfermedades cardiovasculares, son las causasmás importantes de avisa dentro del grupo de enfermedadesno transmisibles...

Objective: to measure the burden of cancer using the indicatorDisability Adjusted Life Years (dalys). Methodology: the useof the dalys indicator made it possible to identify the burden ofcancer in the department of Nariño, 2010. Results: the dalysdueto cancer emphasize the emergency of stomach, cervix, breast,prostate, trachea/bronchus/lung, colon and rectum and benigntumors, as well as leukemias and lymphomas. Similarly, theindicator shows an important amount of years of life lostdue to premature death along with a predominance of thisissue among women. Conclusions: this is the first study ofburden of cancer targeting a department in Colombia using astandardized methodology contributing to the Health Plan ofthe department of Nariño in Colombia during 2013-2015 andto the indicators system of the Cancer Control Ten-Year Plan.Cancer is ranked second only to cardiovascular diseases as themost important causes of dalys within the non communicablediseases group...

Gestión del conocimiento y liderazgo: Perspectivas de relación / Knowledge management and leadership: Relationship prospects

El presente trabajo muestra las relaciones que se han estudiado entre la gestión del conocimiento y el liderazgo con el propósito de comprender mejor la interrelación de ambos constructos. Para ello, en primer lugar se efectúa la revisión teórica de los aspectos centrales de la gestión del conocimiento y el liderazgo, y posteriormente se analizan las relaciones entre los dos conceptos con miras a fijar perspectivas que contribuyan a la determinación de espacios y desarrollo de procesos para la perdurabilidad de las organizaciones. Nuestros resultados señalan la existencia de una fuerte interrelación entre el liderazgo y la gestión del conocimiento, de forma que las empresas precisan de un mayor conocimiento acerca de las características del liderazgo para facilitar la comprensión e implantación de las mejores prácticas en la organización.

This paper shows relationships that have been studied between knowledge management and leadership in order to better understand the interaction between both constructs. With this purpose, we have first performed a theoretical review of the central aspects of knowledge management and leadership, and then we have analyzed the relationship between these concepts in order to set perspectives that contribute to the identification of areas and process development for the sustainability of organizations. Our results indicate the existence of a strong relationship between leadership and knowledge management, so companies need greater knowledge about the characteristics of leadership to facilitate the understanding and implementation of best practices in the organization.