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2.
BMC Pulm Med ; 24(1): 41, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243231

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic resulted in shortages of supplies, which limited the use of extracorporeal membrane oxygenation (ECMO) support. As a contingency strategy, polypropylene (PP) oxygenation membranes were used. This study describes the clinical outcomes in patients on ECMO with PP compared to poly-methylpentene (PMP) oxygenation membranes. METHODS: Retrospective cohort of patients in ECMO support admitted between 2020 and 2021. RESULTS: A total of 152 patients with ECMO support were included, 71.05% were men with an average age of 42 (SD 9.91) years. Veno-venous configuration was performed in 75.6% of cases. The PP oxygenation membranes required more changes 22 (63.1%), than the PMP Sorin® 24 (32,8%) and Euroset® 15 (31,9%) (p.0.022). The main indication for membrane change was low oxygen transfer for PP at 56.2%, Sorin® at 50%, and Euroset® at 14.8%. Renal replacement therapy was the most frequent complication with PP membrane in 22 patients (68.7%) Sorin® 25 patients (34.2%), and Euroset® 15 patients (31.9%) (p 0.001) without statistically significant differences in mortality. CONCLUSION: PP oxygenation membranes was a useful and feasible strategy. It allowed a greater disponibility of ECMO support for critically ill in a situation of great adversity during the SARS-CoV-2 pandemic.


Assuntos
Oxigenação por Membrana Extracorpórea , Polienos , Masculino , Humanos , Adulto , Feminino , Oxigenação por Membrana Extracorpórea/efeitos adversos , Polipropilenos , Estudos Retrospectivos , Pandemias , SARS-CoV-2
4.
One Health ; 17: 100617, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38024258

RESUMO

The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system.

6.
Rev Panam Salud Publica ; 47: e64, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-37123640

RESUMO

This article describes the importance of public-private partnerships (PPPs) and public-private coordination to address antimicrobial resistance (AMR) through the One Health approach. These partnerships are developed between governmental actors, private companies, and social organizations to build agendas, decision-making, and the management of projects of common interest. A case study from Colombia is presented. It describes examples of response from the public sector when the World Health Organization (WHO) reported a colistin resistance alert in 2016; from the animal protein production sector under an industry partnership for the rational use of antimicrobials; and, finally, from a public-private partnership in the swine sector, with governmental institutions and international cooperation, to take action to mitigate the risk of AMR. In Colombia, the establishment of partnerships with organizations representing agricultural producers has generated impactful actions such as strengthening ongoing communication channels between the public and private sectors; characterizing the conditions of the agricultural production chain; establishing mechanisms for consultation and validation of health policies related to AMR; obtaining a baseline of indicator pathogens and identification of possible flows of AMR spread; and, finally, achieving knowledge transfer and capacity-building with national and international experts, with actions to raise awareness about the problem of AMR and its impact on public health. The strategic model developed in Colombia through public-private collaboration can inspire other low- and middle-income countries to optimize their use of resources to obtain results that contribute to the national AMR mitigation plan.


Este artigo descreve a importância das parcerias públicas e das parcerias privadas (PPP) e da articulação público-privada no enfrentamento da resistência a antimicrobianos (RAM) utilizando a abordagem de Saúde Única. Essas parcerias são formadas entre atores governamentais, empresas privadas e organizações sociais para elaborar agendas, tomar decisões e gerir projetos de interesse comum. Este artigo apresenta um estudo de caso da Colômbia, no qual são apresentados exemplos do setor público diante do alerta de resistência à colistina emitido pela Organização Mundial da Saúde (OMS) em 2016, a formação de uma aliança intersetorial pelos setores de produção de proteína animal para promover o uso racional de antimicrobianos e, por último, a formação de uma parceria público-privada composta pelo setor suinícola e por instituições governamentais e cooperação internacional para que a implementação de medidas de mitigação do risco de RAM. Na Colômbia, a criação de parcerias com organizações representantes dos setores de produção agropecuária geraram ações de impacto, como o fortalecimento de canais permanentes de comunicação entre os setores público e privado, a caracterização das condições da cadeia de produção agropecuária, o estabelecimento de mecanismos de consulta e validação das políticas de saúde voltadas para a RAM, a obtenção de uma linha de base de patógenos indicadores e identificação de possíveis fluxos de propagação de RAM e, por fim, a transferência de conhecimentos e capacitação envolvendo especialistas nacionais e internacionais, com ações de conscientização sobre o problema e seu impacto na saúde pública. O modelo estratégico desenvolvido na Colômbia por meio da colaboração público-privada pode inspirar outros países de baixa e média renda a obter resultados, pela otimização de recursos, que contribuam para o plano nacional de mitigação da RAM.

7.
Cancers (Basel) ; 15(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36672296

RESUMO

Cervical cancer (CC) is the fourth most common type of cancer among women; the main predisposing factor is persistent infection by high-risk human papillomavirus (hr-HPV), mainly the 16 or 18 genotypes. Both hr-HPVs are known to manipulate the cellular machinery and the immune system to favor cell transformation. FOXP3, a critical transcription factor involved in the biology of regulatory T cells, has been detected as highly expressed in the tumor cells of CC patients. However, its biological role in CC, particularly in the keratinocytes, remained unclarified. Therefore, this work aimed to uncover the effect of FOXP3 on the biology of the tumoral cells. First, public databases were analyzed to identify the FOXP3 expression levels and the transcribed isoforms in CC and normal tissue samples. The study's findings demonstrated an increased expression of FOXP3 in HPV16+ CC samples. Additionally, the FOXP3Δ2 variant was detected as the most frequent splicing isoform in tumoral cells, with a high differential expression level in metastatic samples. However, the analysis of FOXP3 expression in different CC cell lines, HPV+ and HPV-, suggests no relationship between the presence of HPV and FOXP3 expression. Since the variant FOXP3Δ2Δ7 was found highly expressed in the HPV16+ SiHa cell line, a model with constitutive expression of FOXP3Δ2Δ7 was established to evaluate its role in proliferation, migration, and cell division. Finally, RNAseq was performed to identify differentially expressed genes and enriched pathways modulated by FOXP3Δ2Δ7. The exogenous expression of FOXP3Δ2Δ7 promotes cell division, proliferation, and migration. The transcriptomic analyses highlight the upregulation of multiple genes with protumor activities. Moreover, immunological and oncogenic pathways were detected as highly enriched. These data support the hypothesis that FOXP3Δ2Δ7 in epithelial cells induces cancer-related hallmarks and provides information about the molecular events triggered by this isoform, which could be important for developing CC.

8.
Anticancer Agents Med Chem ; 23(5): 492-497, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35579131

RESUMO

Cervical cancer (CC) is one of the most prevalent cancer-related pathologies in the female population. It is considered the second leading cause of cancer-related deaths in developing countries. The most important etiological factor for the development of CC is the persistent infection with high-risk human papillomavirus. HPV-oncoproteins have evolved to modulate cellular mechanisms to permit viral replication and the generation of new infectious viral particles. When the viral infection persists, there is an uncontrolled viral protein expression essential to commence and maintain the transformation of infected cells. Different cell pathways are affected during the transformation stage, including the NF-κB signaling pathway. NF-κB controls different cellular mechanisms, and its role is critical for various processes, such as immunity, inflammation, cell differentiation, growth, and survival. NF-κB plays a double role in the development of CC. Evidence suggests that in the early stages of viral infection, the NF-κB activity impairs viral transcription and is beneficial for avoiding cellular immortalization. However, in the advanced stages of cervical carcinogenesis, the activation of the NF-κB correlates with a poor prognosis. Here, we discuss some aspects of NF-κB activity during the development of CC and the use of NF-κB inhibitors to treat this pathology.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , NF-kappa B/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/terapia , Transdução de Sinais , Proteínas Oncogênicas/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo
9.
Rev. panam. salud pública ; 47: e64, 2023. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1450309

RESUMO

RESUMEN En este artículo se describe la importancia de las alianzas públicas y las alianzas privadas (APP) y de la articulación público-privada para hacer frente a la resistencia antimicrobiana (RAM) mediante el enfoque Una Salud. Estas alianzas se tejen entre actores gubernamentales, empresas privadas y organizaciones sociales para la construcción de agendas, la toma de decisiones y la gestión de proyectos de interés común. Se presenta un estudio de caso de Colombia, en el que se describen ejemplos del sector público ante la alerta de resistencia a la colistina que la Organización Mundial de la Salud (OMS) informó en el 2016, los sectores productores de proteína animal bajo una alianza intergremial para el uso racional de los antimicrobianos y, por último, una alianza público-privada del sector porcícola con instituciones gubernamentales y cooperación internacional para lograr la implementación de acciones que mitiguen el riesgo de RAM. En Colombia, el establecimiento de alianzas con las organizaciones que representan a los sectores de productores agropecuarios ha generado acciones de impacto, como estrechar canales de comunicación permanente entre el sector público y el privado, caracterizar las condiciones de la cadena de producción agropecuaria, establecer mecanismos de consulta y validación de las políticas de salud en RAM, obtener una línea base de patógenos indicadores e identificación de los posibles flujos de propagación de RAM y, por último, lograr la transferencia de conocimiento y construcción de capacidades con expertos nacionales e internacionales, con acciones de concienciación de la problemática y su impacto en la salud pública. El modelo estratégico desarrollado en Colombia en colaboración público-privada puede inspirar a otros países de bajos y medianos ingresos para obtener resultados, con la optimización de recursos, que contribuyan al plan nacional de mitigación de la RAM.


ABSTRACT This article describes the importance of public-private partnerships (PPPs) and public-private coordination to address antimicrobial resistance (AMR) through the One Health approach. These partnerships are developed between governmental actors, private companies, and social organizations to build agendas, decision-making, and the management of projects of common interest. A case study from Colombia is presented. It describes examples of response from the public sector when the World Health Organization (WHO) reported a colistin resistance alert in 2016; from the animal protein production sector under an industry partnership for the rational use of antimicrobials; and, finally, from a public-private partnership in the swine sector, with governmental institutions and international cooperation, to take action to mitigate the risk of AMR. In Colombia, the establishment of partnerships with organizations representing agricultural producers has generated impactful actions such as strengthening ongoing communication channels between the public and private sectors; characterizing the conditions of the agricultural production chain; establishing mechanisms for consultation and validation of health policies related to AMR; obtaining a baseline of indicator pathogens and identification of possible flows of AMR spread; and, finally, achieving knowledge transfer and capacity-building with national and international experts, with actions to raise awareness about the problem of AMR and its impact on public health. The strategic model developed in Colombia through public-private collaboration can inspire other low- and middle-income countries to optimize their use of resources to obtain results that contribute to the national AMR mitigation plan.


RESUMO Este artigo descreve a importância das parcerias públicas e das parcerias privadas (PPP) e da articulação público-privada no enfrentamento da resistência a antimicrobianos (RAM) utilizando a abordagem de Saúde Única. Essas parcerias são formadas entre atores governamentais, empresas privadas e organizações sociais para elaborar agendas, tomar decisões e gerir projetos de interesse comum. Este artigo apresenta um estudo de caso da Colômbia, no qual são apresentados exemplos do setor público diante do alerta de resistência à colistina emitido pela Organização Mundial da Saúde (OMS) em 2016, a formação de uma aliança intersetorial pelos setores de produção de proteína animal para promover o uso racional de antimicrobianos e, por último, a formação de uma parceria público-privada composta pelo setor suinícola e por instituições governamentais e cooperação internacional para que a implementação de medidas de mitigação do risco de RAM. Na Colômbia, a criação de parcerias com organizações representantes dos setores de produção agropecuária geraram ações de impacto, como o fortalecimento de canais permanentes de comunicação entre os setores público e privado, a caracterização das condições da cadeia de produção agropecuária, o estabelecimento de mecanismos de consulta e validação das políticas de saúde voltadas para a RAM, a obtenção de uma linha de base de patógenos indicadores e identificação de possíveis fluxos de propagação de RAM e, por fim, a transferência de conhecimentos e capacitação envolvendo especialistas nacionais e internacionais, com ações de conscientização sobre o problema e seu impacto na saúde pública. O modelo estratégico desenvolvido na Colômbia por meio da colaboração público-privada pode inspirar outros países de baixa e média renda a obter resultados, pela otimização de recursos, que contribuam para o plano nacional de mitigação da RAM.

10.
One Health ; 15: 100444, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36277084

RESUMO

Zoonotic diseases have serious impacts on human health and well-being, but they are often overlooked in rural Latin America. The design of effective preventive interventions is complex and requires an integrative approach from evidence-based information analyzed through robust theoretical frameworks. We conducted a systematized literature review and qualitative framework-guided thematic analysis to identify social ecological factors affecting the prevention and exposure to zoonotic diseases. Although resources for research are limited in Latin America, we found several studies with relevant results. We extracted and interpreted 8 themes as factors affecting the prevention, transmission, and exposure to zoonosis. These themes included knowledge and misconceptions, low risk perception, gaps in knowledge and communication, psychological effect of diseases, culture and traditions, inequality, disarticulated prevention programs, and organizational responsibility. Alongside this, we compiled and present the recommendations for actions to reduce the impact of zoonoses in these populations. The factors and recommendations here presented can be adapted to inform the design and improvement of preventive programs, focused on One Health and aiming to reduce the impact of zoonotic diseases in rural settings.

11.
Biomater Adv ; 139: 212967, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35882126

RESUMO

Dermal wound healing relies on the properties of the extracellular matrix (ECM). Thus, hydrogels that replicate skin ECM have reached clinical application. After a dermal injury, a transient, biodegradable fibrin clot is instrumental in wound healing. Human plasma, and its main constituent, fibrin would make a suitable biomaterial for improving wound healing and processed as hydrogels albeit with limited mechanical strength. To overcome this, plasma-agarose (PA) composite hydrogels have been developed and used to prepare diverse bioengineered tissues. To date, little is known about the influence of variable agarose concentrations on the viscoelastic properties of PA hydrogels and their correlation to cell biology. This study reports the characterization of the viscoelastic properties of different concentrations of agarose in PA hydrogels: 0 %, 0.5 %, 1 %, 1.5 %, and 2 % (w/v), and their influence on the cell number and mitochondrial activity of human dermal fibroblasts. Results show that agarose addition increased the stiffness, relaxation time constants 1 (τ1) and 2 (τ2), and fiber diameter, whereas the porosity decreased. Changes in cell metabolism occurred at the early stages of culturing and correlated to the displacement of fast (τ1) and intermediate (τ2) Maxwell elements. Fibroblasts seeded in low PA concentrations spread faster during 14 d than cells cultured in higher agarose concentrations. Collectively, these results confirm that PA viscoelasticity and hydrogel architecture strongly influenced cell behavior. Therefore, viscoelasticity is a key parameter in the design of PA-based implants.


Assuntos
Hidrogéis , Engenharia Tecidual , Fibrina , Fibroblastos/metabolismo , Humanos , Hidrogéis/farmacologia , Sefarose , Engenharia Tecidual/métodos
12.
BMC Med Educ ; 22(1): 480, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725443

RESUMO

INTRODUCTION: Exchange transfusion is the treatment of choice for patients with severe hyperbilirubinemia who do not respond to phototherapy. This procedure is highly complex and requires substantial expertise to perform, however it´s not done frequently enough to guarantee adequate training. Traditional learning scenarios do not have a space reserved for teaching this procedure or an instrument that fully and objectively evaluates the skills that a professional must acquire.  OBJECTIVES: The purpose was to construct and evaluate the INEXTUS instrument´s validity evidence relevant to internal structure, in a simulated scenario through the performance of an objective structured clinical exam (OSCE).  MATERIALS AND METHODS: The Delphi consensus methodology was utilized to design the instrument; six experts participated through three rounds using the Google Forms platform. The categories and items previously obtained were subjected to validation by nine experts through a dichotomous survey. Prior to data collection, the evaluators were trained through a pilot test with 10 medical students. Subsequently, all residents of a paediatric programme were evaluated through the OSCE methodology in a simulated scenario, with 6 stations, of a clinical case of a new-born with an explicit need for exchange transfusion. During their participation in the scenario, the residents were first evaluated with the instrument developed. Additionally, audio and video filming of all students who participated was performed with the aim of conducting a second evaluation two weeks after the first four evaluators participated. RESULTS: The final INEXTUS instrument consists of 46 subitems grouped into 23 items divided into 6 categories, demonstrating an inter-rater intraclass correlation coefficient of 0.96 (95% CI 0.94, 0.98 p-value < 0.001). For the Fleiss Kappa of the 23 items evaluated, concordance was evaluated for 14 items but could not be determined for the 9 remaining items because all the ratings were equal, either because the items were not performed or they were all performed adequately. Of the 14 items, 9 good scores were obtained (95% CI 0.61 to 0.8; p value < 0.001), and 5 very good scores were obtained (95% CI 0.81 to 1; p value < 0.001). CONCLUSIONS: The INEXTUS instrument evaluates exchange transfusion skills in medical personnel in training in simulated scenarios using the OSCE methodology; it has high validity and reliability and is a high-impact educational tool.


Assuntos
Competência Clínica , Avaliação Educacional , Estudantes de Medicina , Transfusão de Sangue , Competência Clínica/normas , Avaliação Educacional/métodos , Humanos , Hiperbilirrubinemia/terapia , Reprodutibilidade dos Testes
16.
Int J Biomater ; 2021: 6857204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777502

RESUMO

Multifunctional and biocompatible hydrogels are on the focus of wound healing treatments. Protein and polysaccharides silica hybrids are interesting wound dressing alternatives. The objective of this review is to answer questions such as why silica for wound dressings reinforcement? What are the roles and contributions of silane precursors and silica on the functional properties of hydrogel wound dressings? The effects of tailoring the porous, morphological, and chemical characteristics of synthetic silicas on the bioactivity of hybrid wound dressings hydrogels are explored in the first part of the review. This is followed by a commented review of the mechanisms of silica/protein and silica/polysaccharide interactions and their impact on the barrier, scaffold, and delivery matrix functions of the derived hydrogels. Such information has important consequences for wound healing and paves the way to multidisciplinary researches on the production, processing, and biomedical application of this kind of hybrid materials.

17.
Front Public Health ; 9: 649240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760857

RESUMO

The "One Health" (OH) approach has been recognized by world health authorities such as FAO/OIE/WHO, advocating for effective, multi-sectoral, and transdisciplinary collaboration. However, there is a lack of published evidence of the awareness of the OH concept in Colombia and other countries in the Latin American Region. In order to explore existing collaboration amongst the animal health, human-public health, environmental health sectors, and to describe the perception, knowledge, and barriers on OH in Colombia and other countries of Latin America, an online questionnaire-based survey was distributed among key professionals representing the three OH pillars (August 2018-August 2020). Overall, 76 key respondents from 13 countries (Colombia, México, Chile, Brazil, Argentina, Bolivia, Costa Rica, Ecuador, Perú, Guatemala, Nicaragua Uruguay, and Venezuela) completed the questionnaire. Respondents worked in institutions of animal (59%), public (20%), human (7%), and environmental health (7%); they mainly belonged to higher academic institutions (59%), followed by ministries (11%), and research organizations (9%). Most participants (92%) were familiar with the OH term and 68% were aware of the formal cooperation among sectors in their countries, mostly on zoonoses; in 46% of the cases, such connections were established in the last 5 years. The main reported limiting factors to intersectorality were the lack of commitment of policy-makers, resources, and budget for OH (38%) and the "siloed approach" of sectors and disciplines (34%). Respondents ranked a median score of 3.0 (1-5 scoring) in how good OH activities are implemented in their countries, and a median score of 2.0 in the citizen awareness on OH as regards their countries. The most important OH issues were identified in vector-borne diseases, rabies, wrong and/or improper use of antimicrobials, emerging viral diseases, food-borne diseases, neglected parasitic diseases, deforestation, and ecosystem fragmentation. Although there is a high-perceived importance on conjoint cooperation, OH implementation, and operationalization remain weak, and the environmental component is not well-integrated. We consider that integration and implementation of the OH Approach can support countries to improve their health policies and health governance as well as to advocate the social, economic, and environmental sustainability of the Region.


Assuntos
Saúde Única , Animais , Colômbia , Ecossistema , Humanos , América Latina , Inquéritos e Questionários
18.
Materials (Basel) ; 14(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34361325

RESUMO

We have developed a novel experimental set-up that simultaneously, (i) applies static and dynamic deformations to adherent cells in culture, (ii) allows the visualization of cells under fluorescence microscopy, and (iii) allows atomic force microscopy nanoindentation measurements of the mechanical properties of the cells. The cell stretcher device relies on a dielectric elastomer film that can be electro-actuated and acts as the cell culture substrate. The shape and position of the electrodes actuating the film can be controlled by design in order to obtain specific deformations across the cell culture chamber. By using optical markers we characterized the strain fields under different electrode configurations and applied potentials. The combined setup, which includes the cell stretcher device, an atomic force microscope, and an inverted optical microscope, can assess in situ and with sub-micron spatial resolution single cell topography and elasticity, as well as ion fluxes, during the application of static deformations. Proof of performance on fibroblasts shows a reproducible increase in the average cell elastic modulus as a response to applied uniaxial stretch of just 4%. Additionally, high resolution topography and elasticity maps on a single fibroblast can be acquired while the cell is deformed, providing evidence of long-term instrumental stability. This study provides a proof-of-concept of a novel platform that allows in situ and real time investigation of single cell mechano-transduction phenomena with sub-cellular spatial resolution.

19.
Int J Biomater ; 2021: 9933331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188685

RESUMO

Fibrin is a protein-based hydrogel formed during blood coagulation. It can also be produced in vitro from human blood plasma, and it is capable of resisting high deformations. However, after each deformation process, it loses high amounts of water, which subsequently makes it mechanically unstable and, finally, difficult to manipulate. The objective of this work was to overcome the in vitro fibrin mechanical instability. The strategy consists of adding silica or chitosan-silica materials and comparing how the different materials electrokinetic-surface properties affect the achieved improvement. The siliceous materials electrostatic and steric stabilization mechanisms, together with plasma protein adsorption on their surfaces, were corroborated by DLS and ζ-potential measurements before fibrin gelling. These properties avoid phase separation, favoring homogeneous incorporation of the solid into the forming fibrin network. Young's modulus of modified fibrin hydrogels was evaluated by AFM to quantitatively measure stiffness. It increased 2.5 times with the addition of 4 mg/mL silica. A similar improvement was achieved with only 0.7 mg/mL chitosan-silica, which highlighted the contribution of hydrophilic chitosan chains to fibrinogen crosslinking. Moreover, these chains avoided the fibroblast growth inhibition onto modified fibrin hydrogels 3D culture observed with silica. In conclusion, 0.7 mg/mL chitosan-silica improved the mechanical stability of fibrin hydrogels with low risks of cytotoxicity. This easy-to-manipulate modified fibrin hydrogel makes it suitable as a wound dressing biomaterial.

20.
Hum Gene Ther ; 32(19-20): 1147-1157, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33980038

RESUMO

Inefficient autologous tissue recovery in skin wounds increases the susceptibility of patients to infections caused by multidrug resistant microorganisms, resulting in a high mortality rate. Genetic modification of skin cells has become an important field of study because it could lead to the construction of more functional skin grafts, through the overexpression of antimicrobial peptides that would prevent early contamination and infection with bacteria. In this study, we produce and evaluate human skin equivalents (HSEs) containing transfected human primary fibroblasts and keratinocytes by polyplexes to express the antimicrobial peptide LL-37. The effect of LL-37 on the metabolic activity of normal HSEs was evaluated before the construction of the transfected HSEs, and the antimicrobial efficacy against Pseudomonas aeruginosa and Staphylococcus aureus was evaluated. Subsequently, the levels of LL-37 in the culture supernatants of transfected HSEs, as well as the local expression, were determined. It was found that LL-37 treatment significantly promoted the cellular proliferation of HSEs. Furthermore, HSEs that express elevated levels of LL-37 were shown to possess histological characteristics close to the normal skin and display enhanced antimicrobial activity against S. aureus in vitro. These findings demonstrate that HSEs expressing LL-37 through nonviral modification of skin cells are a promising approach for the prevention of bacterial colonization in wounds.


Assuntos
Peptídeos Antimicrobianos , Staphylococcus aureus , Catelicidinas , Fibroblastos , Humanos , Queratinócitos , Pele
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