Atividade antioxidante e neuroprotetora dos sucos de laranja Citrus sinensis L. Osbeck (Bahia e Cara Cara) no modelo Caenorhabditis elegans

The orange juice, Citrus sinensis L. Osbeck is considered an excellent food source of several bioactive compounds with properties beneficial to human health due to its high content of flavonoids, carotenoids, sugars, minerals and fibers. Some epidemiological and interventional studies have provided evidence to support the inverse correlation between orange juice consumption and the occurrence of cardiovascular disease and cancer. In this study, we used two naturally enriched oranges, originated through spontaneous mutation, called Bahia and Cara Cara. These oranges are high in vitamin C and flavonoids; however, Cara Cara orange is distinguished by being rich in carotenoids (phytoene, phytofluene, lycopene and βcarotene). Considering that oxidative damage and increased neuroinflammation is critically related to pathogenesis and neuronal loss in neurodegenerative diseases, the neuroprotective effect of some components of orange has been of specific interest in the search for effective treatments for these diseases. However, there is still a lack of in vivo studies to show the therapeutic effects of orange juice in its full and complete form, since its compounds have already been shown to have positive antioxidant and neuroprotective effects. In this context, we used the nematode Caenorhabditis elegans which is a widely established model organism for animal behavior, physiology and genetics studies. The objective of this work was to evaluate and compare the antioxidant, neuroprotective and physiological changes related to the aging of the treatment with the pasteurized orange juices Bahia and Cara Cara in the C. elegans model. To perform the experiments, the animals were synchronized in the L1 larval stage and treated at 20 ºC in petri dishes with solid nematode growth medium (NGM), with different concentrations of Bahia or Cara Cara orange juices, seeded with Escherichia coli OP50 or E. coli HT115. The treatment with orange juice provided positive antioxidant effects in C. elegans, such as reduction in endogenous levels of reactive oxygen species (ROS), increased survival under standard and oxidative stress conditions, and increased expression of antioxidant reporter genes - glutamyl cysteine synthetase (gcs-1), glutathione-S-transferase (gst-4) and superoxide dismutase (sod-3) and hsp-16.2 chaperonin. Regarding the neuroprotective effects, it was observed that the orange treatment delays the profile of paralysis induced by the superexpression of the Aβ1-42 peptide in the muscle of the C. elegans model for Alzheimer's disease and decreases the polyglutamine aggregation in the C. elegans model for Huntington's disease. To investigate whether stress response signaling pathways would play an important role in juice effects, ERO quantification, oxidative stress resistance, gst-4::GFP expression, paralysis, and longevity in animals with knockdown were performed. the transcription factors SKN-1, DAF-16 and HSF-1 through interference RNA (RNAi). The results showed that the effects provided by the treatment with Bahia and Cara Cara orange juices were mainly dependent on the SKN-1 and DAF-16 transcription factors, especially SKN-1. In relation to physiological changes related to aging, the treatment increased the life span, the body movements and the rate of pharyngeal beats. We concluded that orange juice treatments provided excellent antioxidant and neuroprotective effects and was able to improve physiological parameters related to aging, which are strongly involved in the quality of life of C. elegans with emphasis on Cara Cara orange juice induced significantly better responses, possibly due to the higher carotenoid content.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)O suco de laranja Citrus sinensis L. Osbeck é considerado uma excelente fonte alimentar de vários compostos bioativos com propriedades benéficas para a saúde humana devido ao seu alto teor de flavonoides, carotenoides, açúcares, minerais e fibras. Alguns estudos epidemiológicos e de intervenção forneceram evidências para apoiar a correlação inversa entre o consumo de suco de laranja e a ocorrência de doenças cardiovasculares e câncer. Neste estudo, utilizamos duas variedades de laranjas, naturalmente enriquecidas, originadas através de mutação espontânea, denominadas Bahia e Cara Cara. Essas laranjas possuem alto teor de vitamina C e flavonoides, no entanto, a laranja Cara Cara se diferencia por também ser rica em carotenoides (fitoeno, fitoflueno, licopeno e βcaroteno). Considerando que o dano oxidativo e o aumento da neuroinflamação estão criticamente relacionados com a patogênese e a perda neuronal em doenças neurodegenerativas, o efeito neuroprotetor de alguns componentes da laranja tem sido de interesse específico na busca de tratamentos eficazes para essas doenças. Contudo, ainda existe carência de estudos in vivo para mostrar os efeitos terapêuticos do suco de laranja em sua forma integral e completa, tendo em vista que de forma isolada seus compostos já demostraram possuir efeitos antioxidantes e neuroprotetores positivos. Nesse contexto, utilizamos o nematodo Caenorhabditis elegans que é um organismo modelo amplamente estabelecido para estudos de comportamento, fisiologia e genética animal. Este trabalho teve com objetivo avaliar e comparar os efeitos antioxidantes, neuroprotetores e as alterações fisiológicas relacionadas ao envelhecimento do tratamento com os sucos de laranja pasteurizados Bahia e Cara Cara no modelo C. elegans. Para a realização dos experimentos, os animais foram sincronizados no estágio larval L1 e tratados a 20 ºC em placas de Petri com meio de crescimento sólido nematoide (NGM), com diferentes concentrações de suco de laranja Bahia ou Cara Cara, semeados com Escherichia coli OP50 ou E. coli HT115. O tratamento com os sucos de laranja proporcionou efeitos antioxidantes positivos no C. elegans como: redução nos níveis endógenos de espécies reativas de oxigênio (ERO), aumento da sobrevivência em condições padrão e de estresse oxidativo e aumento na expressão dos genes repórteres antioxidantes - glutamil cisteína sintetase (gcs-1), glutationa-S-transferase (gst-4) e superóxido dismutase (sod-3) e da chaperonina hsp-16.2. Em relação aos efeitos neuroprotetores, foi observado que o tratamento com laranja retarda o perfil de paralisia induzido pela super-expressão do peptídeo A1- 42 no músculo do modelo C. elegans para o Mal de Alzheimer e diminui a agregação poliglutamínica no modelo C. elegans para a doença de Huntington. Para investigar se as vias de sinalização de resposta ao estresse desempenhariam um papel importante nos efeitos dos sucos, foram realizados ensaios de quantificação de ERO, resistência ao estresse oxidativo, expressão de gst4::GFP, paralisia e longevidade em animais com knockdown para os fatores de transcrição SKN-1, DAF-16 e HSF-1 através de RNA de interferência (RNAi). Os resultados mostraram que os efeitos proporcionados pelo tratamento com os sucos de laranja Bahia e Cara Cara foram dependentes principalmente dos fatores de transcrição SKN-1 e DAF-16, com destaque para SKN-1. Em relação às alterações fisiológicas relacionadas ao envelhecimento, o tratamento aumentou o tempo de vida, os movimentos corporais e a taxa de batimentos faríngeos. Concluimos que os tratamentos com os sucos de laranja proporcionaram excelentes efeitos antioxidantes, neuroprotetores e ainda foram capazes de melhorar parâmetros fisiológicos relacionados ao envelhecimento, que estão fortemente envolvidos na qualidade de vida do C. elegans, com destaque para o suco de laranja Cara Cara que induziu respostas significativamente melhores, possivelmente devido ao maior teor de carotenoides

Local and regional components of aerosol in a heavily trafficked street canyon in central London derived from PMF and cluster analysis of single-particle ATOFMS spectra.

Positive matrix factorization (PMF) has been applied to single particle ATOFMS spectra collected on a six lane heavily trafficked road in central London (Marylebone Road), which well represents an urban street canyon. PMF analysis successfully extracted 11 factors from mass spectra of about 700,000 particles as a complement to information on particle types (from K-means cluster analysis). The factors were associated with specific sources and represent the contribution of different traffic related components (i.e., lubricating oils, fresh elemental carbon, organonitrogen and aromatic compounds), secondary aerosol locally produced (i.e., nitrate, oxidized organic aerosol and oxidized organonitrogen compounds), urban background together with regional transport (aged elemental carbon and ammonium) and fresh sea spray. An important result from this study is the evidence that rapid chemical processes occur in the street canyon with production of secondary particles from road traffic emissions. These locally generated particles, together with aging processes, dramatically affected aerosol composition producing internally mixed particles. These processes may become important with stagnant air conditions and in countries where gasoline vehicles are predominant and need to be considered when quantifying the impact of traffic emissions.This is the author accepted manuscript. The final version is available via ACS at http://pubs.acs.org/doi/abs/10.1021/es506249z

Hydrophilic and hydrophobic polymeric benznidazole-loaded nanoparticles: physicochemical properties and in vitro antitumor efficacy

Benznidazole is a promising antitumor drug because it has the ability to induce the production of intracellular reactive oxygen species. In this study, poly(D, L-lactide-co-glycolide), a hydrophobic polymer, and Eudragit (R) E PO, a hydrophilic polymer, were used to prepare nanoparticles and evaluated for their abilities to improve drug antitumor efficacy. Nanoparticles were prepared using the emulsification-solvent evaporation method. Particle size, zeta potential, encapsulation efficiency, attenuated total reflectance Fourier transformation infrared spectroscopy, and in vitro drug release were assessed for all formulations. Formulations with Eudragit (R) E PO produced cationic (> + 25 mV) nanoparticles, which were smaller (< 160 nm) than those prepared with poly (D, L-lactide-co-glycolide) (< 250 nm), which were negatively charged (-2 mV). Use of poly(D, L-lactide-co-glycolide) resulted in the highest encapsulation efficiency. However, the hydrogel characteristics of Eudragit (R) E PO resulted in the slowest drug release rate. Cytotoxicity assays using the human embryonic kidney cell line HEK 293, the human liver cancer cell line Hep G2, and the human colon cancer cell line HT-29 demonstrated that nanoparticle formulations with the two polymers improved the biological activity of benznidazole. However, cationic and hydrophilic nanoparticles induced greater cytotoxicity. This study provided useful information regarding preformulation of polymeric nanoparticles to improve drug uptake

Cannabidiol in the treatment of migraine: studies and future perspectives

Introduction: Migraine is one of the most disabling and prevalent conditions in the population. Is related to the release of pro-inflammatory mediators in the central nervous system, triggering painful episodes. Cannabidiol (CBD) has significant potential to inhibit such pro-inflammatory mediators and consequently reduce pain symptoms. Objective: To describe the progression of a patient diagnosed with refractory migraine, analyzing the relationship between CBD use and symptom improvement. Case Report: A 37-year-old female patient from Teresina has been patient with refractory migraine for 1 year. She has experienced headaches since the age of 11, with sporadic episodes that improved with dipyrone use. There was an increase in frequency, occurring three times a week, with improvement after using non-steroidal anti-inflammatory drugs. She was undergoing psychiatric treatment, using benzodiazepine and antipsychotic. A year ago, she consulted a neurologist, complaining of a headache lasting 38 days, with a pain score of 8/10 VAS, refractory to NSAIDs, with throbbing pain in the occipital region radiating to the cervical area, associated with photophobia, phonophobia, and aura, which worsened with physical exertion and stress. She was treated with topiramate, oral corticosteroids, and beta-blockers for control, and triptan for acute relief. Due to the lack of response to initial treatment, she used anticonvulsant and muscle relaxant, along with lifestyle changes. However, with the persistence of pain, anticonvulsant and antipsychotic were added to her regimen alongside topiramate. Given the inefficacy in pain control, treatment with progressive doses of cannabidiol was initiated at 20 mg/day, with an increase of 25 mg/week, along with continuous anticonvulsant use. There was an improvement in the headache with symptom resolution by the fourth week. Currently, she uses 1 mL/day (50 mg/mL) of CBD, reporting one episode of headache (VAS 6/10) after a month of CBD use, relieved with triptan. Conclusion:The diagnosis and treatment of migraine should be individualized for each patient. In this context, the therapeutic use of cannabidiol for treatment-refractory migraine cases is a recent alternative in the scientific literature, requiring further studies to be effectively understood and established as a potential approach for a broad spectrum of disease manifestations.      

Self-assembled benznidazole-loaded cationic nanoparticles containing cholesterol/sialic acid: physicochemical properties, in vitro drug release and in vitro anticancer efficacy

Cationic polymeric nanoparticles (NPs) have the ability to overcome biological membranes, leading to improved efficacy of anticancer drugs. The modulation of the particle-cell interaction is desired to control this effect and avoid toxicity to normal cells. In this study, we explored the surface functionalization of cationic polymethylmethacrylate (PMMA) NPs with two natural compounds, sialic acid (SA) and cholesterol (Chol). The performance of benznidazole (BNZ) was assessed in vitro in the normal renal cell line (HEK-293) and three human cancer cell lines, as follows: human colorectal cancer (HT-29), human cervical carcinoma (HeLa), and human hepatocyte carcinoma (HepG2). The structural properties and feasibility of NPs were evaluated and the changes induced by SA and Chol were determined by using multiple analytical approaches. Small (<200 nm) spherical NPs, with a narrow size distribution and high drug-loading efficiency were prepared by using a simple and reproducible emulsification solvent evaporation method. The drug interactions in the different self-assembled NPs were assessed by using Fourier transform-infrared spectroscopy. All formulations exhibited a slow drug-release profile and physical stability for more than 6 weeks. Both SA and Chol changed the kinetic properties of NPs and the anticancer efficacy. The feasibility and potential of SA/Chol-functionalized NPs has been demonstrated in vitro in the HEK-293, HepG2, HeLa, and HT-29 cell lines as a promising system for the delivery of BNZ.</p

Cross-Education In Individuals With Parkinson’s Disease: A Randomized Controlled Trial

INTRODUCTION: People with Parkinson’s disease (PD) usually have one side of their bodies more affected than the other. Our hypothesis is that unilateral resistance training (RT) may cause changes in motor control and strength of the most affected side when compared with bilateral RT. OBJECTIVE: To investigate the effects of unilateral vs bilateral RT on motor control and strength in individuals with PD. METHOD: The sample consisted of 17 individuals diagnosed with PD, who were randomly divided into unilateral training group (UTG) (n = 9) and bilateral training group (BTG) (n = 8). In total, 24 RT sessions were performed. The first six training sessions were focused on training familiarization. Before (T0), during (T12), and after (T24) the intervention, the following data were collected: fine motor control using the Nine-Hole Peg test and the Box and Blocks test; upper limb strength using a handgrip strength dynamometer; and lower limb strength using an isokinetic dynamometer. All tests were performed unilaterally. For statistical analysis of data, the Friedman analysis of variance (ANOVA) [3 (TIME) × 4 (GROUP)] was used, as well as the Mann-Whitney U test and the Wilcoxon test. RESULTS: Peak torque at 60º/s on the right side at T12 in UTG was significantly higher compared with BTG. Peak torque on the right side was significantly lower at T24 compared with T12 and T0 in UTG. CONCLUSION: Short-term unilateral RT was inefficient at causing changes in motor control and strength in the limb most affected by the disease through cross-education and was unable to reduce bilateral deficit

Associação entre nível de independência funcional e percepção subjetiva da dor em idosos no pósoperatório de artroplastia de quadril

A artroplastia de quadril (AQ) é um procedimento cirúrgico que consiste na substituição da articulação lesionada por uma prótese. O pós-operatório pode reduzir a independência funcional e repercutir na percepção subjetiva da dor em idosos. O estudo avaliou a associação entre o nível de independência funcional e a percepção subjetiva da dor em idosos submetidos à AQ. Trata-se de um estudo transversal, descritivo, quantitativo e de associação. A medida de independência funcional (MIF) foi utilizada para avaliar o nível de independência funcional, e a escala visual analógica (EVA) foi empregada para avaliar a percepção subjetiva da dor. O teste de correlação de Spearman foi utilizado para verificar a associação entre a MIF e a EVA, e uma regressão linear simples, para analisar a influência de uma variável sobre a outra (p≤0,05). Um total de 48 idosos foram avaliados, com média de idade de 71,5±9 anos, em que 37,5% (n=18) pertenciam ao sexo masculino e 62,5% (n=30) ao feminino. A avaliação da EVA mostrou uma média de 3,5 (±1,6), enquanto a MIF, 107 (±17,82). Observamos uma associação significante e inversa com p=0,006 e com r de −0,389, com R2 de 0,142. Este estudo mostrou que há uma relação inversamente proporcional entre a sensação subjetiva da dor e o nível de independência funcional de idosos no pós-operatório de AQ. A partir disso, é necessário que os profissionais da saúde deem mais atenção ao quadro álgico desses idosos, visando otimizar sua recuperação funcional a fim de aumentar sua independência funcional.La artroplastia de cadera (AC) es un procedimientoquirúrgico que reemplaza la articulación lesionada por una prótesis.El postoperatorio puede reducir la independencia funcional y afectarla percepción subjetiva del dolor en el anciano. Este estudio evaluó laasociación entre el nivel de independencia funcional y la percepciónsubjetiva del dolor en ancianos sometidos a AC. Se trata de un estudiotransversal, descriptivo, cuantitativo y de asociación. La medida deindependencia funcional (MIF) se utilizó para evaluar el nivel deindependencia funcional, y la escala visual analógica (EVA), paraestimar la percepción subjetiva del dolor. Se aplicaron la pruebade correlación de Spearman para verificar la asociación entre MIFy EVA, y una regresión lineal simple para analizar la influencia deuna variable sobre la otra (p≤0,05). Participaron 48 ancianos,de edad media de 71,5±9 años; de los cuales el 37,5% (n=18) erandel sexo masculino y el 62,5% (n=30) del sexo femenino. La mediade la evaluación de EVA fue de 3,5 (±1,6), mientras que la de MIF,de 107 (±17,82). Hubo una asociación significativa e inversa conp=0,006 y con r de −0,389, con R2de 0,142. Este estudio demostróuna relación inversamente proporcional entre la sensación subjetivade dolor y el nivel de independencia funcional de los ancianos en elpostoperatorio de AC. Por lo tanto, es necesario que los profesionalesde la salud tengan mayor atención al dolor de esta población, con elobjetivo de optimizarle la recuperación funcional y, así, aumentarsu independencia funcionalHip replacement (HR) is a surgery that replacesthe injured joint with a prosthesis. The postoperative periodcan reduce functional independence and affect the subjectiveexperience of pain in older adults. This study evaluated theassociation between the level of functional independenceand the subjective experience of pain in older adults whounderwent HR. This cross-sectional descriptive quantitativeassociation study used the functional independencemeasure (FIM) to assess the level of functional independenceand the visual analogue scale (VAS) to analyze the subjectiveexperience of pain. Spearman’s correlation test was used toevaluate the association between FIM and VAS and simplelinear regression to analyze the influence of one variableon another (p≤0.05). This study evaluated 48 older adults,with a mean age of 71.5±9 years, of which 37.5% (n=18) weremen and 62.5% (n=30) were women. The mean VAS and FIMvalues were 3.5 (±1.6) and 107 (±17.82), respectively, and theyhad a significant and inverse association (p=0.006; r=−0.389;R2 and the level of functional independence in older patients whounderwent HR. Therefore, health professionals should pay moreattention to pain in these patients in order to optimize theirfunctional recovery and increase their functional independence=0.142). This study showed an inversely proportionalrelationship between the subjective experience

Impacto da Telemedicina na obstétricia no contexto da Atenção Primária à Saúde: revisão de literatura

Introduction: Telemedicine is the practice of Medicine through the use of interactive audiovisual data communication methodologies, with the objective of health care, education and research. Objective: To demonstrate the impact of telemedicine on obstetric care in primary health care. Methodology: This is an integrative literature review using the Google Scholar database, with the inclusion criteria being articles published between 2018 and 2024, available free of charge in Portuguese and English, which addressed the objectives of the theme. Results and Discussion: Technologies become an ally in improving the quality of care offered to pregnant women, ensuring comprehensive and continuous care, bringing primary care and maternity closer together, promoting educational actions, reducing obstetric clinical errors, including family members and people in contact with the pregnant woman, thus providing better obstetric care. Conclusion: Therefore, telemedicine offers benefits such as increased access to consultations and monitoring of the health of pregnant women, especially in remote regions or regions with a shortage of specialized professionals, reducing geographical and logistical barriers, promoting the reduction of complications during pregnancy and childbirthIntrodução: A telemedicina é o exercício da Medicina através da utilização de metodologias interativas de comunicação audiovisual de dados, com o objetivo de assistência, educação e pesquisa em saúde. Objetivo: Demonstrar o impacto da telemedicina na Atenção obstétrica na Atenção primária à Saúde. Metodologia: trata-se de uma revisão integrativa da literatura utilizando a base de dados google acadêmico, tendo como critérios de inclusão artigos publicados entre 2018 a 2024, disponíveis gratuitamente na língua portuguesa e inglesa, que abordavam os objetivos da temática. Resultados e Discussão: A tecnologias tornam-se um aliado para melhorar a qualidade da assistência ofertada a gestantes, assegurando o cuidado integral e de forma contínua, aproximação entre a atenção básica e a maternidade, promoção de ações educativas, diminui os erros clínicos obstétricos, engloba os familiares e pessoas em contato com a gestante, assim proporcionando melhor assistência obstétrica. Conclusão: Portanto, a telemedicina oferece benefícios como a ampliação do acesso às consultas e ao monitoramento da saúde da gestante, especialmente em regiões remotas ou com escassez de profissionais especializados, a redução das barreiras geográficas e logísticas, promovendo a redução de complicações durante a gestação e no parto. &nbsp