Desenvolvimento de curativos anti-inflamatórios à base de amido utilizando moléculas derivadas de subprodutos do tomate

Most wound dressings currently used are not ideal for a total, fast, and effective healing process due to their reduced biocompatibility derived from their synthetic nature and lack of bioactive properties. Alternatively, new bio-based dressings with antimicrobial and/or anti-inflammatory activity have been developed. However, the natural polymers currently used come from food, acting as competitors for human nutrition. Agrifood byproducts-derived biomolecules can help overcome this competition. In this work, the feasibility of using tomato byproducts-derived molecules for the development of starch-based dressings with anti-inflammatory properties was studied. For this purpose, the influence of tomato pomace-derived hot-water soluble extract concentration (1%, 5%, and 10% w/w in relation to starch dry weight), rich in polysaccharides (TE) and/or phenolic compounds (PE), on the chromatic, mechanical, physicochemical, and active properties (antimicrobial and anti-inflammatory) of starch-based films obtained by solvent casting was studied. In a circular economy concept, starch was recovered from industrial potato processing slurries. TE and PE extracts showed, respectively, 14.7% and 18.5% of protein, 43.7% and 28.6% of polysaccharides, 2.8% and 15.1% of phenolic compounds, and promising antioxidant activity (IC50 values of 2.5 mg/mL and 0.8 mg/mL, respectively). When incorporated into starch-based formulations, TE and PE allowed to develop transparent films with a yellowish coloration and less rigid and traction resistant films than the control films. TE originated hydrophobic and flexible films, while PE decreased the films’ hydrophobicity and stretchability. Regarding the active properties, after 24h, both films with TE and PE revealed anti-inflammatory activity in the presence of a pro-inflammatory agent, where, for starch-based films with 10% TE and 10% PE, the inflammation decreased by ca. 48% and 100%, respectively. To develop starch-based dressings, in this work the electrospinning of starch-based solutions was also optimized. After adjusting the solvent, starch concentration, and dissolution time, starch-based fibers were obtained, although in small amount for application in the development of dressings. The tomato pomace-derived molecules and starch recovered from potato washing slurries have shown to be promising raw materials for the development of biobased anti-inflammatory dressings, which will allow to promote more biocompatible and functional wound healing devices than the materials derived from inert synthetic polymers.Muitos dos curativos para feridas atualmente utilizados não são os ideais para um processo de cura total, rápido e eficaz devido à sua reduzida biocompatibilidade, oriunda da sua natureza sintética e da ausência de propriedades funcionais. Como alternativa têm sido desenvolvidos novos curativos de origem biológica com atividade antimicrobiana e/ou anti inflamatória. No entanto, os polímeros de origem natural até à data utilizados provêm de alimentos, atuando como competidores para a alimentação humana. As biomoléculas derivadas dos subprodutos da indústria agroalimentar podem ajudar a superar esta competição. Neste trabalho foi estudada a viabilidade da utilização de moléculas derivadas dos subprodutos de tomate para o desenvolvimento de pensos à base de amido com propriedades anti-inflamatórias. Para o efeito foi estudada a influência da concentração (1%, 5% e 10% m/m em relação à massa seca de amido) de extratos solúveis em água quente derivados to repiso de tomate, ricos em polissacarídeos (TE) e/ou compostos fenólicos (PE), nas propriedades cromáticas, mecânicas, físico-químicas e ativas (anti-inflamatórias e antimicrobianas) dos filmes à base de amido obtidos pelo método de evaporação do solvente. Num conceito de economia circular, o amido foi recuperado de lamas provenientes do processamento industrial de batata. Os extratos TE e PE apresentaram, respetivamente, 14,7% e 18,5% de proteína, 43,7% e 28,6% de polissacarídeos, 2,8% e 15,1% de compostos fenólicos e promissora atividade antioxidante (IC50 de 2,5 mg/mL e 0,8 mg/mL, respetivamente). Quando incorporados em formulações à base de amido, os extratos TE e PE permitiram desenvolver filmes transparentes com coloração amarelada e menor rigidez e resistência à tração do que os filmes controlo. TE originou filmes hidrofóbicos e flexíveis, enquanto PE diminuiu a hidrofobicidade e extensibilidade dos filmes. Quanto às propriedades ativas, ambos os filmes com TE e PE demostraram atividade anti-inflamatória quando na presença de um agente pró-inflamatório, observando-se, ao fim de 24 h, uma diminuição da inflamação de cerca de 48% e 100% para os filmes à base de amido com 10% de TE e PE, respetivamente. Com o intuito de desenvolver pensos à base de amido, neste trabalho também se otimizou a eletrofiação de soluções à base de amido. Após o ajuste do solvente, da concentração de amido e do tempo necessário para a sua dissolução foram obtidas fibras à base amido, porém em baixa quantidade para posterior aplicação no desenvolvimento de pensos. As biomoléculas existentes no repiso de tomate e o amido recuperado das lamas de lavagem de batata mostraram-se promissores para o desenvolvimento de curativos anti-inflamatórios de origem biológica, o que permitirá promover dispositivos médicos para cura de feridas mais biocompatíveis e funcionais dos que os materiais derivados de polímeros sintéticos inertes.Mestrado em Biotecnologi

Clinical Study DHA Supplementation during Pregnancy and Lactation Affects Infants' Cellular but Not Humoral Immune Response

Background. It is currently recommended that diet of pregnant mothers contain 200-300 mg DHA/day. Aim. To determine whether DHA supplementation during pregnancy and lactation affects infants' immune response. Methods. 60 women in ≥3rd pregnancy studied; 30 randomly assigned to receive DHA 400 mg/day from 12th week gestation until 4 months postpartum. From breast-fed infants, blood obtained for anti-HBs antibodies, immunoglobulins, lymphocyte subset phenotyping, and intracellular cytokine production. Results. CD4+ lymphocytes did not differ between groups, but CD4CD45RA/CD4 (naïve cells) significantly higher in infants in DHA+ group. Proportion of CD4 and CD8 cells producing IFN γ significantly lower in DHA+ group, with no differences in proportion of IL4-producing cells. Immunoglobulins and anti-HBs levels did not differ between groups. Conclusions. In infants of mothers receiving DHA supplementation, a higher percentage of CD4 naïve cells and decreased CD4 and CD8 IFN γ production is compatible with attenuation of a proinflammatory response

Safety, Tolerability, and Effects of Sodium Bicarbonate Inhalation in Cystic Fibrosis.

BACKGROUND:Among the many consequences of loss of CFTR protein function, a significant reduction of the secretion of bicarbonate (HCO3-) in cystic fibrosis (CF) is a major pathogenic feature. Loss of HCO3- leads to abnormally low pH and impaired mucus clearance in airways and other exocrine organs, which suggests that NaHCO3 inhalation may be a low-cost, easily accessible therapy for CF. OBJECTIVE:To evaluate the safety, tolerability, and effects of inhaled aerosols of NaHCO3 solutions (4.2% and 8.4%). METHODS:An experimental, prospective, open-label, pilot, clinical study was conducted with 12 CF volunteer participants over 18 years of age with bronchiectasis and pulmonary functions classified as mildly to severely depressed. Sputum rheology, pH, and microbiology were examined as well as spirometry, exercise performance, quality-of-life assessments, dyspnea, blood count, and venous blood gas levels. RESULTS:Sputum pH increased immediately after inhalation of NaHCO3 at each clinical visit and was inversely correlated with rheology when all parameters were evaluated: [G' (elasticity of the mucus) = - 0.241; G″ (viscosity of the mucus) = - 0.287; G* (viscoelasticity of the mucus) = - 0.275]. G* and G' were slightly correlated with peak flow, forced expiratory volume in 1 s (FEV1), and quality of life; G″ was correlated with quality of life; sputum pH was correlated with oxygen consumption (VO2) and vitality score in quality of life. No changes were observed in blood count, venous blood gas, respiratory rate, heart rate, peripheral oxygen saturation of hemoglobin (SpO2), body temperature, or incidence of dyspnea. No adverse events associated with the study were observed. CONCLUSION:Nebulized NaHCO3 inhalation appears to be a safe and well tolerated potential therapeutic agent in the management of CF. Nebulized NaHCO3 inhalation temporarily elevates airway liquid pH and reduces sputum viscosity and viscoelasticity

Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

<p>Abstract</p> <p>Background</p> <p>Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D₃(1,25(OH)₂D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the <it>PHEX </it>gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies.</p> <p>Methods</p> <p>Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the <it>PHEX </it>gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test.</p> <p>Results</p> <p>Mutations in the <it>PHEX </it>gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)₂D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013).</p> <p>Conclusions</p> <p><it>PHEX </it>gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious <it>PHEX </it>mutations had lower TRP and 1,25(OH)₂D levels suggesting that the <it>PHEX </it>type of mutation might predict the XLHR phenotype severity.</p

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P &lt; 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P &lt; 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P &lt; 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P &lt; 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P &lt; 0.001; OR(BP) = 2.4, P &lt; 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P &lt; 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P &lt; 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Sepharadim/conversos and premodern Global Hispanism

Sepharadim participated in the Hispanic vernacular culture of the Iberian Peninsula. Even in the time of al-Andalus many spoke Hispano-Romance, and even their Hebrew literature belies a deep familiarity with and love of their native Hispano-Romance languages. However, since the early sixteenth century the vast majority of Sepharadim have never lived in the Hispanic world. Sepharadim lived not in Spanish colonies defined by Spanish conquest, but in a network of Mediterranean Jewish communities defined by diasporic values and institutions. By contrast, the conversos, those Sepharadim who converted to Catholicism, whether in Spain or later in Portugal, Italy, or the New World, lived mostly in Spanish Imperial lands, were officially Catholic, and spoke normative Castilian. Their connections, both real and imagined, with Sephardic cultural practice put them at risk of social marginalization, incarceration, even death. Some were devout Catholics whose heritage and family history doomed them to these outcomes. Not surprisingly, many Spanish and Portugese conversos sought refuge in lands outside of Spanish control where they might live openly as Jews. This exodus (1600s) from the lands formerly known as Sefarad led to a parallel Sephardic community of what conversos who re-embraced Judaism in Amsterdam and Italy by a generation of conversos trained in Spanish universities. The Sephardic/Converso cultural complex exceeds the boundaries of Spanish imperial geography, confuses Spanish, Portuguese, Catholic, and Jewish subjectivities, and defies traditional categories practiced in Hispanic studies, and are a unique example of the Global Hispanophone