Nanomedicines for the delivery of antimicrobial peptides (AMPs)

Microbial infections are still among the major public health concerns since several yeasts and fungi, and other pathogenic microorganisms, are responsible for continuous growth of infections and drug resistance against bacteria. Antimicrobial resistance rate is fostering the need to develop new strategies against drug-resistant superbugs. Antimicrobial peptides (AMPs) are small peptide-based molecules of 5–100 amino acids in length, with potent and broad-spectrum antimicrobial properties. They are part of the innate immune system, which can represent a minimal risk of resistance development. These characteristics contribute to the description of these molecules as promising new molecules in the development of new antimicrobial drugs. However, efforts in developing new medicines have not resulted in any decrease of drug resistance yet. Thus, a technological approach on improving existing drugs is gaining special interest. Nanomedicine provides easy access to innovative carriers, which ultimately enable the design and development of targeted delivery systems of the most efficient drugs with increased efficacy and reduced toxicity. Based on performance, successful experiments, and considerable market prospects, nanotechnology will undoubtedly lead a breakthrough in biomedical field also for infectious diseases, as there are several nanotechnological approaches that exhibit important roles in restoring antibiotic activity against resistant bacteria.Elena Sanchez-Lopez belongs to 2017SGR-1477. Elena Sanchez-Lopez, Marta Espina and Maria L. GarciaacknowledgethesupportfromtheInstituteofNanoscienceandNanotechnology(ART2018project). Eliana B. Souto acknowledges the Portuguese Science and Technology Foundation (FCT/MCT) and European Funds (PRODER/COMPETE) for the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), co-funded by FEDER, under the partnership Agreement PT2020. Maria C. Teixeira wishes to acknowledge FCT for the individual fellowship (PD/BDE/135086/2017).info:eu-repo/semantics/publishedVersio

Application of Dielectric Barrier Discharge (DBD) atmospheric pressure plasma for pretreatment of medical textiles

Conventional pretreatment by wet chemistry and/or low-pressure plasma have several drawbacks [1]. Atmospheric plasma is an alternative and cost-competitive method to low-pressure plasma and wet chemical pretreatments, allowing continuous and uniform processing of fibers, substrates and films surfaces, improving its functionalization performance [2]. This technology has been studied in the field of the R&D project - PLASMAMED. The main objective of this project is to produce a new generation of coatings containing nanoparticles (NPs) and enzybiotics, with controllable antibacterial activity, on medical textiles, with special emphasis in antimicrobial dressing for pressure injury and hernia meshes. To achieve this goal, a dielectric barrier discharge (DBD) atmospheric pressure plasma was used as a pretreatment sustainable alternative. In this sense, medical-grade 100% polyester (PES) fabrics were pretreated by atmospheric plasma technology, where various processing conditions were tested. Different treatment speeds and discharges powers were tested, as well as the application of various gases (such as helium, oxygen and nitrogen) and a corona treatment (air), with a carrier gas (argon). The characterization of these pretreated textiles was carried out by contact angle (CA), through the sessile drop technique, with 3 µL water droplets on the surface of the textile. In general, contact angles exhibit a significant decrease (between 40º and 60º for all studied gases), when compared with the standard values for substrate without treatment (around 120º). Therefore, plasma pretreatment significantly improved the hydrophilicity of these fabrics (Figure 1), which reveals to be an advantage for the further functionalization step

Idiopathic Pulmonary Fibrosis in the Era of Antifibrotic Therapy: Searching for New Opportunities Grounded in Evidence

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that up to now has been associated with a poor prognosis. However, the results of the INPULSIS and ASCEND trials and the approval of nintedanib and pirfenidone have marked the beginning of a new era for IPF patients. Questions remain, however. Should these drugs be used earlier? What effect will they have on more severe disease? Will their effects last beyond the trial period? This manuscript is the outcome of a multidisciplinary meeting between pulmonology, radiology, and pathology clinicians on the use of antifibrotic agents in IPF. In our opinion, the existing data show that pirfenidone and nintedanib slow functional decline in early stages of disease. These drugs also appear to result in therapeutic benefits when administered to patients with advanced disease at diagnosis and maintain effective over time. The data also suggest that continuing antifibrotic therapy after disease progression may confer benefits, but more evidence is needed. Early diagnosis and treatment are crucial for reducing functional decline, slowing disease progression, and improving quality of life.info:eu-repo/semantics/publishedVersio

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

β-cyclodextrin/isopentyl caffeate inclusion complex: synthesis, characterization and antileishmanial activity

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in -cyclodextrin (-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.This research was funded by Banco do Nordeste (grant FUNDECI/2016.0015), Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (PROCESSO: 88887.159533/2017-00 extração, encapsulação e caracterização de bioativos para o interesse biotecnologico). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301964/2019-0 Chamada 06/2019, and Chamada CNPq nº 01/2019) and from the Portuguese Science and Technology Foundation (FCT) project UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Modelagem e produção de espidroína sintética de seda de aranha para aplicações biomédicas.

Sedas de aranhas são biopolímeros com extraordinárias características físico‑químicas. Elas podem ser processadas e utilizadas em diversos biomateriais inovadores como partículas, além da forma natural de fibras. Entretanto, por causa da limitação da obtenção desse material in natura, é necessário o desenvolvimento de sistemas de produção heteróloga de proteínas de seda de aranha (espidroínas). Neste trabalho, buscou‑se, por meio da biologia sintética, a produção de uma espidroína em Eschericha coli BL21(DE3). A espidroína sintética foi baseada na sequência da proteína MaSp2 da aranha do Cerrado brasileiro Parawixia bistriata, aqui denominada Engenheirada 1 (Eng1). Para isso, a espidroína Eng1 foi sintetizada no plasmídeo pET24a, contendo um peptídeo‑sinal de secreção de uma β‑xilosidase e mais oito repetições da região de interesse da MaSp2, além de regiões bioativas para endereçamento celular. As bactérias foram transformadas, e as proteínas foram produzidas por autoindução em frasco Erlenmeyer de 2 L. Logo após, as células foram precipitadas por centrifugação, e o sobrenadante foi concentrado por ultrafiltração para posterior purificação das espidroínas por cromatografia de afinidade. A produção da Eng1, com 33,54 kDa, foi confirmada por SDS‑PAGE corado com nitrato de prata e Western blot. A partir deste trabalho, foi possível desenvolver um sistema heterólogo para a produção de espidroínas sintéticas de sedas de aranhas. A vantagem deste sistema está na capacidade do peptídeo‑sinal de secretar a espidroína sintética para o meio de cultura

Growth And Mineral Nutrition Of Neem ( Azadirachta indica A. Juss.) And Chinaberry Tree (Melia azedarach Linn.) Submitted To Salinity

Este trabalho teve como objetivo verificar os efeitos da salinidade do solo no crescimento e no ac\ufamulo de macronutrientes e de s\uf3dio em nim (Azadirachta indica) e cinamomo ( Melia azedarach ). O experimento foi disposto em delineamento experimental inteiramente casualizado em arranjo fatorial 2 x 4, sendo duas esp\ue9cies (nim e cinamomo) e quatro n\uedveis de salinidade (Condutividade el\ue9trica (C.E.) 0,49 (solo n\ue3o salino); 4,15; 6,33 e 10,45 dS m-1), com 4 repeti\ue7\uf5es. As plantas cresceram inicialmente em tubetes e, 60 dias ap\uf3s a emerg\ueancia, foram transferidas para vasos contendo 3 kg de substrato [solo + esterco (2:1)], de acordo com o tratamento de salinidade. Ap\uf3s 45 dias foram avaliadas altura das plantas, mat\ue9ria seca (folhas, caule, parte a\ue9rea (caule + folhas), ra\uedzes e total) e ac\ufamulo de N, P, K, Ca, Mg, S e Na+ na parte a\ue9rea. A salinidade reduziu a altura das plantas em ambas as esp\ue9cies, mas o efeito foi mais pronunciado no nim. Eleva\ue7\ue3o na salinidade dos solos causou aumento no ac\ufamulo de Na+ e redu\ue7\ue3o no ac\ufamulo de macronutrientes na parte a\ue9rea em ambas as esp\ue9cies, principalmente no nim. O cinamomo foi mais tolerante aos n\uedveis de salinidade dos solos do que o nim.The objective of this study was to verify the effects of soil salinity on growth and nutrient and sodium accumulation in neem (Azadirachta indica) and cinnamomum ( Melia azedarach ). The experimental delineation was completely randomized in a 2 x 4 factorial arrangement, with two species (neem and cinnamomum), four salinity levels (electrical conductivity 0.49 (non saline soil), 4.15, 6.33 and 10.45 dS m-1) and four replications. Initially, plants were grown in tubes, and 60 days after emergence, they were transferred to pots containing 3 kg of substrate [soil + manure (2:1)], according to the saline treatment. After 45 days, plant height, dry matter (leaves, stem, shoot (stem + leaves), roots and total) and N, P, K, Ca, Mg, S and Na+ shoot accumulation were evaluated. Salinity reduced the plant height in both species, but the effect was more pronounced in neem. Increases in soil salinity caused an increase in the accumulation of Na+ and reduced the accumulation of nutrients in shoots of both species, especially in neem. The cinnamomum was more tolerant to salinity levels of soils than neem

The use of zootherapeutics in folk veterinary medicine in the district of Cubati, Paraíba State, Brazil

<p>Abstract</p> <p>Background</p> <p>The present work addresses the use of zootherapy in folk veterinary medicine (ethnoveterinary) by the residents of the municipal district of Cubati, microregion of Seridó, Paraíba State, Brazil. It sought to identify the principal animals used as medicinal sources for zootherapeutics and to contribute to the preservation and sustainability of this traditional knowledge.</p> <p>Methods</p> <p>Field research was undertaken on a weekly or biweekly basis during the period November, 2006, to January, 2007. Free, semi-structured, and open interviews were made with local residents of the municipal district of Cubati (in both urban and rural settings) as well as with venders in public markets. A total of 25 individuals of both sexes were interviewed (with ages varying from 26 to 78 years) although only 16 were finally chosen as informants as these people demonstrated the greatest degree of knowledge concerning zootherapeutics. Graphs and percentages were generated using Microsoft^©Excel 2007 software, and the species were identified by photographic registration and subsequent bibliographical surveys.</p> <p>Results</p> <p>Mammals constitute the main medicinal zootherapeutic source for folk veterinary medicines in the studied area, both in terms of the total number of species used and the frequency of their citation. Sheep (<it>Ovis aries</it>), pigs (<it>Sus scrofa</it>), cattle (<it>Bos taurus</it>), and foxes (<it>Cerdocyon thous</it>) were mentioned by 62.5, 43.75, 37.5, and 31.25% of the informants, respectively, as being used in folk veterinary medicine. Additionally, chameleons (<it>Iguana iguana</it>), chickens (<it>Gallus domesticus</it>), and rattlesnakes (<it>Crotalus durissus</it>) were mentioned by 75, 43.75, and 31.25% of the informants, respectively. Relatively simple animal illnesses, such as furuncles, or injuries resulting from embedded thorns or skin eruptions are responsible for the largest number of zootherapeutic treatment, while, diseases of greater complexity, such as rabies and brucellosis, were not even mentioned. Fat from various animals constituted the most frequently cited resource used for its medicinal-veterinary properties.</p> <p>Conclusion</p> <p>The examination of folk knowledge and health practices allows a better understanding of human interactions with their local environment, and aids in the formulation of appropriate strategies for natural resource conservation.</p