Efeitos do ?leo de pequi (Caryocar brasiliense) em elementos da resposta imune da mucosa intestinal de camundongos alimentados com dieta hiperlip?dica

Evid?ncias cient?ficas apontam que compostos da dieta, tais como ?cidos graxos monoinsaturados (MUFA) e carotenoides, em sua forma isolada ou extra?da, parecem modular a resposta imune da mucosa intestinal. O ?leo de pequi (OP) ? rico em MUFA e carotenoides. N?s mostramos previamente efeito imunomodulador do OP na mucosa intestinal de camundongos saud?veis e com colite ulcerativa aguda. Entretanto, este efeito ainda n?o foi investigado no contexto da obesidade. O objetivo deste estudo foi investigar efeitos do ?leo de pequi sobre elementos da resposta imune da mucosa intestinal de camundongos alimentados com dieta hiperlip?dica. Para tal, 48 camundongos C57BL/6 machos foram distribu?dos em quatro grupos: C, que recebeu dieta controle, CP que recebeu dieta C e OP; HL que recebeu dieta hiperlip?dica e HLP, que recebeu dieta HL e OP. O OP foi ofertado diariamente em uma dose de 150 mg. O experimento teve dura??o de 10 semanas. Foram avaliados indicadores cl?nicos da obesidade, biomarcadores metab?licos sangu?neos e os fen?tipos de leuc?citos do compartimento intraepitelial e das placas de peyer da mucosa do intestino delgado e dos linfonodos mesent?ricos. As massas corporais finais do grupo HLP se igualaram ?s dos grupos C e CP e foram igualmente inferiores ao grupo HL (p<0,05). Apesar de o ganho de massa corporal do grupo HLP ter sido inferior ao HL (p<0,05), n?o se igualou ao C e ao CP. A ingest?o alimentar di?ria dos grupos HLP e CP foi igualmente menor que a do grupo C e ambas superiores ao HL (p<0,05). A menor ingest?o cal?rica foi a do grupo CP (p<0,05) e n?o houve diferen?a entre HL e HLP. Os animais que ingeriram OP (CP e HLP) tiveram a adiposidade visceral semelhante ao grupo C e inferior ao HL (p<0,05). A toler?ncia ? glicose foi menor para os animais dos grupos HL e HLP em compara??o aos controles (C e CP) (p<0,05). O OP na dieta controle reduziu a contagem global de leuc?citos no sangue (p<0,05), mas este efeito foi perdido quando ele foi ingerido na dieta hiperlip?dica. No compartimento intraepitelial, o OP elevou os leuc?citos totais tanto no grupo CP quanto no grupo HLP e n?o afetou os linf?citos intraepiteliais em compara??o ao HL (p<0,05). Por outro lado, a dieta hiperlip?dica elevou os linf?citos T?? e n?o houve efeito do OP (p<0,05). Nos linfonodos mesent?ricos, houve aumento percentual dos linf?citos para o grupo HLP em rela??o aos grupos C e HL, por?m n?o foi significativo. Houve uma redu??o dos lint?citos T auxiliares no grupo CP em rela??o ao C (p<0,05). Nas placas de peyer os leuc?citos totais aumentaram no grupo HLP em rela??o aos grupos HL e C (p<0,05). N?o houve altera??es expressivas nos demais tipos celulares entre os tratamentos. O ?leo de pequi promoveu um aumento de leuc?citos totais no epit?lio intestinal do grupo HLP, possivelmente c?lulas da imunidade inata, como os macr?fagos M2, com consequente reparo do epit?lio intestinal, uma vez que os animais alimentados com dieta hiperlip?dica e ?leo de pequi apresentaram redu??o da massa corporal.Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq)Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG)Disserta??o (Mestrado) ? Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2020.Scientific evidence has shown that diet compounds, such as monounsaturated fatty acids (MUFA) and carotenoids, in their isolated or extracted form, seem to modulate the immune response of the intestinal mucosa. Pequi oil (PO) is high in MUFA and carotenoids. We previously showed immunomodulatory effects of PO in the intestinal mucosa of healthy mice and with acute ulcerative colitis. However, this effect has not yet been investigated in the context of obesity. This study aimed to investigate PO effects on elements of the immune response of the intestinal mucosa of mice fed a high-fat diet. 48 C57BL/6 male mice were distributed into four groups: C, fed chow, CP fed chow and PO; HF fed a high-fat diet and HFP, fed HF and PO. The PO was offered at a 150 mg daily dose. The bioassay lasted 10 weeks. Clinical indicators of obesity, blood metabolic biomarkers, and the phenotypes of leukocytes from the intraepithelial compartment and Peyer's patches from intestinal mucosa and mesenteric lymph nodes were evaluated. Body mass from HFP was equal to C and CP groups, being equally lower than HF (p<0.05). Although body mass gain of the HFP group was lower than HF (p<0.05), it did not match to C and CP. Daily food intake of HFP and CP groups was also lower than C, being both higher than HF (p<0.05). The lowest caloric intake was form the CP group (p<0.05) and there was no difference between HF and HFP. PO animals (CP and HFP) had visceral adiposity similar to the C group and lower than HF (p<0.05). Glucose tolerance was lower for HF and HFP groups compared to controls (C and CP) (p<0.05). The PO in the control diet reduced the overall blood leukocytes count (p<0.05), but this effect was lost when it was ingested in the high-fat diet (HFP). In the intestinal mucosa, PO elevated the total leukocytes in both CP and HFP groups and it did not affect intraepithelial lymphocytes compared to HF (p<0.05). Otherwise, high-fat diet elevated T?? lymphocytes and there was no effect of PO (p<0.05). In the mesenteric lymph nodes, there was an increase in intraepithelial lymphocytes for the HFP group compared to C and HF groups, but it was not significant. There was a reduction in auxiliary T lymphocytes in the CP group compared to C (p<0.05). In the Peyer's patches the leukocytes increased in the HFP group compared to HF and C groups (p<0.05). There were no significant changes in the other cell types between treatments. Pequi oil in a high-fat diet promoted an increase in immune cells from intestinal mucosa, possible macrophages, with consequent intestinal epithelium repair, which at last, may have contributed to lose body mass

X-ray Structure And Molecular Dynamics Simulations Of Endoglucanase 3 From Trichoderma Harzianum: Structural Organization And Substrate Recognition By Endoglucanases That Lack Cellulose Binding Module.

Plant biomass holds a promise for the production of second-generation ethanol via enzymatic hydrolysis, but its utilization as a biofuel resource is currently limited to a large extent by the cost and low efficiency of the cellulolytic enzymes. Considerable efforts have been dedicated to elucidate the mechanisms of the enzymatic process. It is well known that most cellulases possess a catalytic core domain and a carbohydrate binding module (CBM), without which the enzymatic activity can be drastically reduced. However, Cel12A members of the glycosyl hydrolases family 12 (GHF12) do not bear a CBM and yet are able to hydrolyze amorphous cellulose quite efficiently. Here, we use X-ray crystallography and molecular dynamics simulations to unravel the molecular basis underlying the catalytic capability of endoglucanase 3 from Trichoderma harzianum (ThEG3), a member of the GHF12 enzymes that lacks a CBM. A comparative analysis with the Cellulomonas fimi CBM identifies important residues mediating interactions of EG3s with amorphous regions of the cellulose. For instance, three aromatic residues constitute a harboring wall of hydrophobic contacts with the substrate in both ThEG3 and CfCBM structures. Moreover, residues at the entrance of the active site cleft of ThEG3 are identified, which might hydrogen bond to the substrate. We advocate that the ThEG3 residues Asn152 and Glu201 interact with the substrate similarly to the corresponding CfCBM residues Asn81 and Arg75. Altogether, these results show that CBM motifs are incorporated within the ThEG3 catalytic domain and suggest that the enzymatic efficiency is associated with the length and position of the substrate chain, being higher when the substrate interact with the aromatic residues at the entrance of the cleft and the catalytic triad. Our results provide guidelines for rational protein engineering aiming to improve interactions of GHF12 enzymes with cellulosic substrates.8e5906

X-ray structure and molecular dynamics simulations of endoglucanase 3 from Trichoderma harzianum: structural organization and substrate recognition by endoglucanases that lack cellulose binding module

Plant biomass holds a promise for the production of second-generation ethanol via enzymatic hydrolysis, but its utilization as a biofuel resource is currently limited to a large extent by the cost and low efficiency of the cellulolytic enzymes. Considerable efforts have been dedicated to elucidate the mechanisms of the enzymatic process. It is well known that most cellulases possess a catalytic core domain and a carbohydrate binding module (CBM), without which the enzymatic activity can be drastically reduced. However, Cel12A members of the glycosyl hydrolases family 12 (GHF12) do not bear a CBM and yet are able to hydrolyze amorphous cellulose quite efficiently. Here, we use X-ray crystallography and molecular dynamics simulations to unravel the molecular basis underlying the catalytic capability of endoglucanase 3 from Trichoderma harzianum (ThEG3), a member of the GHF12 enzymes that lacks a CBM. A comparative analysis with the Cellulomonas fimi CBM identifies important residues mediating interactions of EG3s with amorphous regions of the cellulose. For instance, three aromatic residues constitute a harboring wall of hydrophobic contacts with the substrate in both ThEG3 and CfCBM structures. Moreover, residues at the entrance of the active site cleft of ThEG3 are identified, which might hydrogen bond to the substrate. We advocate that the ThEG3 residues Asn152 and Glu201 interact with the substrate similarly to the corresponding CfCBM residues Asn81 and Arg75. Altogether, these results show that CBM motifs are incorporated within the ThEG3 catalytic domain and suggest that the enzymatic efficiency is associated with the length and position of the substrate chain, being higher when the substrate interact with the aromatic residues at the entrance of the cleft and the catalytic triad. Our results provide guidelines for rational protein engineering aiming to improve interactions of GHF12 enzymes with cellulosic substrates.FAPESP (08/56255-9, 09/54035-4, 10/08680-2)CNPq (490022/2009-0, 550985/2010-7

Protoporphyrin IX Associated with Visible Light for the Treatment of Trichophyton rubrum Causing Onychomycosis - An Updated Review

Systemic medications used during the treatment of onychomycosis caused by Trichophyton rubrum may have relapse, making them costly and insignificant for the patient. Photodynamic therapy (PDT) is an advantageous therapeutic option for disease control, mainly due to the absence of risk of microbial resistance. The action of PDT is combined by three elements: photosensitizer (PS), visible light (VL) and molecular oxygen, leading to the formation of reactive oxygen species (ROS) or singlet oxygen formation (1O2), both ROS (type I mechanism) as 1O2 (type II mechanism) induce damage and death to microbial cells. This research was proposed as a study through a non-systematic review, to investigate the action of PS "Protoporphyrin IX" (Pp IX) associated with visible light on T. rubrum, contemplating clinical and relevant data regarding the treatment of onychomycosis by PDT. PubMed survey was conducted from June 2021 to April 2022. The research strategy included clinical trials, randomized trials, systematic reviews, meta-analyses and reviews in English. Pp IX has affinity for T. rubrum, which is justified by the incorporation of Pp IX into the cell membrane, which led to inhibition by LV irradiation. Thus, the photodynamic process of Pp IX may lead to cell death by type I and II mechanisms. The data found are promising, however, new studies in vitro and in vivo are suggested, since few studies have been found related to the theme

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Percepção dos pais sobre a implantação da estratégia de fortificação da alimentação infantil com micronutrientes

Objective: To assess parents’ perception of the implementation of the strategy for the fortification of child food with micronutrient powders (NutriSUS). Methods: Qualitative descriptive and exploratory study conducted from August to September 2015 with 11 mothers of children enrolled in preschool programs in Montes Claros, Minas Gerais, Brazil. Data were collected using a semi-structured questionnaire and then underwent content analysis from which two thematic categories emerged: “Importance of NutriSUS” and “Schools as healthpromoting environments”. Results: Parents showed to be aware of the importance/benefits of NutriSUS given the increase in child’s appetite and provision of a nutritionally enriched diet. They also had a positive perception of the strategy of partnership between the school and the health center and of the school as a health-promoting environment. Conclusion: Parents’ reports indicated that they understood the objective of the fortification strategy and the importance of a healthy diet in the first years of life. This knowledge contributes to improve the support for the growth and development of Brazilian children given that parents are important agents for the effectiveness of the strategy.Objetivo: Analizar la percepción de los padres de los alumnos sobre la implantación de la estrategia de fortificación de la alimentación infantil con micronutrientes en polvo (NutriSUS). Métodos: Investigación cualitativa, descriptiva y exploratoria realizada en los meses de agosto y septiembre de 2015 con 11 madres de alumnos matriculados en el Centro de Educación Infantil de la ciudad de Montes Claros, MG, Brasil. Los datos fueron recogidos a través de una entrevista semiestructurada y analizados a través de la técnica de análisis de contenido con la identificación de dos categorías temáticas “La Importancia del NutriSUS” y “Las escuelas como ambiente de promoción de la salud”. Resultados: Los padres demuestran algún conocimiento sobre la importancia/el beneficio del NutriSUS reconocido por el aumento del apetito de sus hijos y el entendimiento de la oferta de una alimentación más rica de nutrientes. Ellos presentaron uma percepción positiva de la estrategia de acuerdo entre la escuela y la unidad de salud y la escuela como ambiente de promoción de la salud. Conclusión: El relato de los padres indicó su comprensión del objetivo de la estrategia de fortificación y la importancia de una alimentación saludable en los primeros años de vida. Esse conocimiento contribuye para mejorar el apoyo al crecimiento y desarrollo de niños brasileños ya que los padres son factores condicionantes para la efectividad de esa estrategia.Objetivo: Analisar a percepção dos pais dos educandos acerca da implantação da estratégia de fortificação da alimentação infantil com micronutrientes em pó (NutriSUS). Métodos: Pesquisa qualitativa, descritiva e exploratória, realizada nos meses de agosto e setembro de 2015, com 11 mães de alunos matriculados nos Centros de Educação Infantil da cidade de Montes Claros, MG, Brasil. Os dados foram coletados por meio de uma entrevista semiestruturada, sendo analisados pela técnica de análise de conteúdo, sendo identificadas duas categorias temáticas “Importância do NutriSUS” e as “Escolas como ambiente promotor de saúde”. Resultados: Os pais demonstraram algum conhecimento sobre a importância/ benefício do NutriSUS, reconhecido pelo aumento do apetite dos seus filhos e o entendimento da oferta de uma alimentação mais enriquecida nutricionalmente. Eles ainda apresentaram uma percepção positiva da estratégia de parceria entre escola e unidade de saúde e a escola como ambiente promotor de saúde. Conclusão: O relato dos pais indicou que eles compreendem o objetivo da estratégia de fortificação e a importância de uma alimentação saudável nos primeiros anos de vida. Esse conhecimento contribui para melhorar o suporte ao crescimento e desenvolvimento das crianças brasileiras uma vez que os pais são agentes condicionantes para a efetividade dessa estratégia

Implantação da estratégia de fortificação da alimentação infantil em um município do Sudeste do Brasil: relato de experiência

As crianças encontram-se mais vulneráveis quanto à deficiência de micronutrientes, sendo um público prioritário para a destinação de políticas de prevenção de carências nutricionais. Assim, este relato de experiência descreve a implantação da Estratégia de Fortificação da Alimentação Infantil com Micronutrientes em pó (NutriSUS), que visa principalmente combater a anemia ferropriva, dentre outras deficiências nutricionais, enfatizando o cotidiano nas creches participantes da estratégia no decorrer da implantação, bem como, o objetivo do relato. Participaram das descrições sete creches pertencentes ao Programa Saúde na Escola (PSE), que foram contempladas com o NutriSUS. O período de duração da implantação foi de, aproximadamente, um ano. Ressalta-se a importância desse relato no que tange ao fornecimento de subsídio para a promoção dessa estratégia e, também, da parceria entre as Secretarias de Saúde e Educação, contribuindo para o fortalecimento de ações de desenvolvimento integral das crianças