Dietary Leucine Supplementation Minimises Tumour-induced Damage In Placental Tissues Of Pregnant, Tumour-bearing Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats. Results: Pregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20th day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid-injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits. Conclusions: Consumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth.1658FAPESP [2010/00209-9, 2011/08276-0, 2013/16115-1]CNPq [302863/2013-3]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Dietary leucine supplementation minimises tumour-induced damage in placental tissues of pregnant, tumour-bearing rats

Background: The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats. Results: Pregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20th day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid-injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits. Conclusions: Consumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth16CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP302863/2013-32010/00209-9; 2011/08276-0; 2013/16115-

GENETIC PARAMETERS IN SEED CHARACTERS OF Ormosia discolor UNDER DIFFERENT AMBIENT CONDITIONS

Ormosia discolor Spruce ex Benth. is a native tree of the Amazon with has fast growth and nodulation capacity, whose seeds are used for craftwork. The objective of this study was to estimate genetic parameters in seed characters of O. discolor at different ambient temperatures and to indicate superior matrices to compose seed lots. Seeds of 20 progenies selected from a population in the state of Amazonas were collected. Three experiments were performed under different ambient temperatures at the Seed Center laboratory/UFAM. Experiment 1 was performed at constant temperature of 30 °C. In experiment 2, seeds were submitted to a temperature of 35 °C. In experiment 3, after five months of freezing, the seeds were submitted to a temperature of 30 °C. The experimental design was completely randomized, consisting of 20 progenies, four replicates, and 25 seeds per plot. The germination characters evaluated were germination rate, mean germination time, and synchronization and speed germination indexes. Genetic and phenotypic variances and correlations, broad-sense heritability, and genetic gain through direct selection were estimated. O.discolor progenies showed significant genetic variability for most of the characters evaluated. High heritability and accuracy values (> 90%) were found for germination rates at all ambient temperatures. Matrices 2, 7, and 16 were superior for germination characters at all temperatures tested, being indicated for seedling production. Eighteen O. discolor seeds are sufficient for biometric analysis with accuracy of 95% in genotype selection.

Tumoral Resection followed by Blepharoplasty in Squamous Cell Carcinoma Treatment in the Lower Eyelid of a Horse

Background: Equines are routinely subjected to enucleation due to palpebral tumors. Blepharoplasties in horses, especially in the lower eyelid, are rarely performed due to the difficulty of sliding once the tissue around the eyes presents low mobility. Defects involving more than 50% of the lower eyelid is considered challenging after tumor removal. Squamous cell carcinoma (SCC) is the second most reported neoplasm in horses, being very common in regions of the lower eyelid, third eyelid, sclera and or cornea. The aim of this study is to present the Destro VY skin advancement flap as a blepharoplasty technique performed after surgical excision of a SCC, with total commitment of the lower eyelid, completely covering the right eye of a mare.Case: A 8-year-oldmarePaint Horse, weighing420 kg,was referred for evaluation of tumor tissue of 6.0 x 4.0 x 2.0 cm, with nodular and ulcerated appearance, involving the right lower eyelid, in its total extension and completely covering the eye, without adhering to it. Considering the initial suspicion of SCC, the treatment strategy performed was surgical eyelid excision and maintenance of the eye, followed by blepharoplasty as an attempt to reconstruct the eyelid. Under general inhalation anesthesia, the animal was placed in left lateral recumbency, when the surgical region was prepared and local anesthetic block was performed. After antisepsis, a skin incision was made circumscribing the tumor, respecting a margin of 10 mm apart and excision of all visible tumor tissue was performed followed by intralesional ozone therapy. Blepharoplasty was performed to cover the portions of the exposed lacrimal and zygomatic bones, as well as correction of the eyelid aesthetics. For this, Destro VY skin advancement flap was performed for reconstruction of the lower eyelid. An incision of approximately 7 cm in V-shaped skin was performed, and the subcutaneous tissue under the V was dissected, maintaining a central pedicle, responsible for the vascularization of the flap, which was slid, approximately 20 mm, towards the eye. After obtaining the desired skin approximation, Y-suture was performed, covering the exposed bone and reconstructing the lower eyelid. In the postoperative period, local instillation of mitomycin eye drops and systemic meloxicam administration were instituted. The mare had her vision restored, presenting satisfactory morpho functional and aesthetic results and no tumor recurrence during 1-year of follow-up. Discussion: The repair of lower eyelid imperfections is challenging, especially when they have large defects, and there are no reports of performing the Destro VY skin advancement flap technique in horses for lower eyelid reconstruction. In this case, the importance of the blepharoplasty technique is emphasized, avoiding enucleation, preserving horse’s vision and aesthetics. In addition, aiming to avoid tumor recurrence, especially if surgical safety margins can not be achieved, other complementary treatments should be associated, including intralesional ozone therapy, mitomycin, an antineoplastic chemotherapy drug, and meloxicam, a COX-2 selective, non-steroidal anti-inflammatory drug, as performed in this study. It is concluded that the use of the Destro VY skin advancement flap technique for reconstruction of the external lamella in cases of SCC in the lower eyelid of horses is a feasible technique, which preserves the animal's vision, as well as aesthetics. The safety margin in the surgical excision of the SCC and the association of complementary therapies in the resolution of the condition are important points also to be considered.Keywords: epidermoid carcinoma, equine, ophthalmology, plastic surgery, skin tumor. Título: Exérese tumoral seguida de blefaroplastia no tratamento de carcinoma de células escamosas em pálpebra inferior de equino

Leucine and Its Importance for Cell Signalling Pathways in Cancer Cachexia-Induced Muscle Wasting

The anabolic effects of a supplemented diet with branched-chain amino acids, especially leucine, on skeletal muscle wasting and as a co-adjuvant in cancer treatment have been well-studied. Leucine is a precursor of protein synthesis and acts as a nutritional signal, affecting multiple metabolic processes (e.g., satiety, thermogenesis, energy efficiency, and body composition). Previous studies related to nutritional therapy have mainly focused on myopenia, which is the loss of skeletal muscle mass in some pathologies, including cancer. Leucine plays a role in the maintenance and even increase of lean body mass in healthy individuals as well as the prevention of disease states that culminate in myopenia. Herein, we review the available data addressing the mechanisms by which leucine acts as a cellular signal, thereby stimulating muscle protein synthesis, leading to the inhibition of muscle catabolism, especially in an experimental model of cancer cachexia. We also show differences found in the metabolomic and proteomic analyses, including the use of leucine in maternal diets as a preventative for muscle wasting as supported by our experimental data

VIVÊNCIAS DE MULHERES PRIVADAS DE LIBERDADE EM TODO PERÍODO GESTACIONAL

RESUMO Objetivo: Compreender as vivências das mulheres privadas de liberdade acerca da assistência ao pré-natal, maternidade e puerpério no sistema prisional. Método: Trata-se de uma pesquisa qualitativa, descritiva, referenciada pela análise de conteúdo por Laurence Bardin realizada no período de 2021, com a participação de seis mulheres que vivenciaram o pré-natal, parto ou puerpério em um sistema penitenciário feminino na região de Belo Horizonte participaram de uma entrevista com roteiro semiestruturado.  Utilizou para coleta de dados a técnica de Snowball “bola de neve”. O projeto de pesquisa foi aprovado pelo Comitê de Ética em Pesquisa da PUC/Minas pelo parecer CAAE:  62515416,3,0000.5137 em consonância com os aspectos éticos e legais da Resolução 466/12 das pesquisas envolvendo seres humanos. Resultados: Cinco categorias foram identificadas: “Fragilidade na assistência ao pré-natal, parto e puerpério às mulheres privadas de liberdade”; “Estigma em relação ao atendimento apropriado e humanizado ao binômio mãe-filho”; “Sentimento de solidão vivenciado desde o início da gestação até a separação do binômio mãe-filho”; “A esperança por um futuro melhor em decorrência do amor surgido pelo filho e o “Medo e a angústia decorrente da separação do binômio mãe-filho”. Conclusão: O estudo apontou diversas lacunas no processo da assistência ao pré-natal, parto e puerpério no sistema prisional, tais como: estrutura física, e estigma na assistência às mulheres privadas de liberdade. Portanto, percebe-se a necessidade de uma assistência à saúde de qualidade e que atenda as premissas do Sistema Único de Saúde.   PALAVRAS-CHAVE: Saúde da Mulher; Serviços de Saúde; Sistema Prisional; Gestação; Indicadores de Morbimortalidade

CARACTERIZAÇÃO EPIDEMIOLÓGICA E HISTOPATOLÓGICA DAS NEOPLASIAS MAMÁRIAS DE FELINOS EM FORTALEZA E REGIÃO METROPOLITANA

Mammary neoplasms are one of the three most neoplasms common types in female domestic cats, with an occurrence of 20 cases and a frequency of 33.90% in animals aged 10 to 12 years. Factors such as the use of hormones, pseudocyesis, obesity, and a diet rich in lipids in the young phase may be a part of the etiology of this pathologyin cats. There is a high rate of malignancy in most feline mammary tumors, most being carcinomas corresponding to 42.86% of the cases. The most common benign neoplasms are adenomas. The prognosis is reserved for most cats, and death is usually caused by clinical effects secondary to the progression of the local disease (disease located in the mammarychain) or due to metastatic spread to vital organs. Thus, the diagnosis is of extreme importance for a good prognosis. The present work aimed at the epidemiological and histopathological characterization of mammary neoplasms in felines in the city of Fortaleza and its metropolitan region, analyzing data from 59 histopathological exams of mammary tissue samples of this species.As neoplasias mamárias são um dos três tipos neoplásicos mais frequentes nas fêmeas de gatos domésticos, sendo observada a ocorrência de 20 casos e frequência de 33,90% em animais com idade de 10 a 12 anos. Fatores como a utilização de hormônios, pseudociese, obesidade e alimentação rica em lipídeos na fase jovem podem estar envolvidos na etiologia desta patologia mamária em gatas. Existe um alto índice de malignidade na maioria dos tumores mamários felinos, sendo a maior parte carcinomas com 42,86% dos casos verificados. As neoplasias benignas mais comuns são os adenomas. O prognóstico é reservado para a maioria das gatas, sendo a morte geralmente causada por efeitos clínicos secundários à progressão da doença local (doença localizada na cadeia mamária) ou devido à disseminação metastática para órgãos vitais. Desta forma, o diagnóstico é de extrema importância para um bom prognóstico. O presente trabalho teve como objetivo a caracterização epidemiológica e histopatológica das neoplasias mamárias em felinos no município de Fortaleza e região metropolitana, fazendo uma análise de dados de 59 exames histopatológicos de amostras de tecido mamário desta espécie

Explorando Abordagens Terapêuticas Baseadas em Evidências para a Prevenção do Suicídio

  In this analysis, different therapeutic interventions for suicide prevention are explored, addressing a variety of innovative techniques and approaches. Initially, the effectiveness of psychotherapeutic interventions is highlighted, which involve approaches such as cognitive-behavioral therapy, interpersonal therapy, and acceptance and commitment therapy. These approaches have shown promising results in reducing the risk of suicide and promoting the mental well-being of individuals at risk. In addition to psychotherapeutic interventions, pharmacological strategies are discussed, involving the use of psychotropic medications to treat underlying conditions such as depression and bipolar disorder, which increase the risk of suicide. Although these medications are widely used, their long-term efficacy and potential side effects remain areas of evolving research. Another important aspect is the approach of technology-based interventions, such as mobile applications and online platforms, which provide emotional support, offer educational resources, and facilitate access to mental health services. These technologies have the advantage of reaching a large number of people in an accessible and convenient manner. In addition to therapeutic interventions, the importance of a collaborative and multidisciplinary approach to suicide prevention is emphasized. This includes coordination among psychiatrists, psychologists, social workers, emergency teams, and family members to provide a comprehensive and personalized support network for individuals in crisis. In summary, evidence-based therapeutic approaches play a crucial role in suicide prevention, offering effective options for those at risk. However, careful patient assessment and an individualized approach are essential to ensure the best outcomes and long-term safety of individuals in crisis.Nesta análise, são exploradas diferentes intervenções terapêuticas para a prevenção do suicídio, abordando uma variedade de técnicas e abordagens inovadoras. Inicialmente, destaca-se a eficácia das intervenções psicoterapêuticas, as quais envolvem abordagens como terapia cognitivo-comportamental, terapia interpessoal e terapia de aceitação e compromisso. Essas abordagens têm demonstrado resultados promissores na redução do risco de suicídio e na promoção do bem-estar mental dos indivíduos em risco. Além das intervenções psicoterapêuticas, são discutidas as estratégias farmacológicas, as quais envolvem o uso de medicamentos psicotrópicos para tratar condições subjacentes, como depressão e transtorno bipolar, que aumentam o risco de suicídio. Embora esses medicamentos sejam amplamente utilizados, sua eficácia a longo prazo e seus potenciais efeitos colaterais continuam sendo áreas de investigação em evolução. Outro aspecto importante é a abordagem de intervenções baseadas em tecnologia, como aplicativos móveis e plataformas online, que oferecem suporte emocional, fornecem recursos educacionais e facilitam o acesso a serviços de saúde mental. Essas tecnologias têm a vantagem de alcançar um grande número de pessoas de forma acessível e conveniente. Além das intervenções terapêuticas, enfatiza-se a importância de uma abordagem colaborativa e multidisciplinar na prevenção do suicídio. Isso inclui a coordenação entre psiquiatras, psicólogos, assistentes sociais, equipes de emergência e familiares para fornecer uma rede de apoio abrangente e personalizada para indivíduos em crise. Em resumo, as abordagens terapêuticas baseadas em evidências desempenham um papel crucial na prevenção do suicídio, oferecendo opções eficazes para aqueles em risco. No entanto, é essencial uma avaliação cuidadosa do paciente e uma abordagem individualizada para garantir os melhores resultados e a segurança a longo prazo dos indivíduos em crise

Leucine-Rich Diet Modulates the Metabolomic and Proteomic Profile of Skeletal Muscle during Cancer Cachexia

Background: Cancer-cachexia induces a variety of metabolic disorders, including skeletal muscle imbalance. Alternative therapy, as nutritional supplementation with leucine, shows a modulatory effect over tumour damage in vivo and in vitro. Method: Adult rats distributed into Control (C), Walker tumour-bearing (W), control fed a leucine-rich diet (L), and tumour-bearing fed a leucine-rich diet (WL) groups had the gastrocnemius muscle metabolomic and proteomic assays performed in parallel to in vitro assays. Results: W group presented an affected muscle metabolomic and proteomic profile mainly related to energy generation and carbohydrates catabolic processes, but leucine-supplemented group (WL) recovered the energy production. In vitro assay showed that cell proliferation, mitochondria number and oxygen consumption were higher under leucine effect than the tumour influence. Muscle proteomics results showed that the main affected cell component was mitochondria, leading to an impacted energy generation, including impairment in proteins of the tricarboxylic cycle and carbohydrates catabolic processes, which were modulated and improved by leucine treatment. Conclusion: In summary, we showed a beneficial effect of leucine upon mitochondria, providing information about the muscle glycolytic pathways used by this amino acid, where it can be associated with the preservation of morphometric parameters and consequent protection against the effects of cachexia

Leucine-rich diet induces a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, reducing glucose consumption and metastasis in Walker-256 tumour-bearing rats

Leucine can stimulate protein synthesis in skeletal muscle, and recent studies have shown an increase in leucine-related mitochondria! biogenesis and oxidative phosphorylation capacity in muscle cells. However, leucine-related effects in tumour tissues are still poorly understood. Thus, we described the effects of leucine in both in vivo and in vitro models of a Walker-256 tumour. Tumour-bearing Wistar rats were randomly distributed into a control group (W; normoprotein diet) and leucine group (LW; leucine-rich diet [normoprotein +3% leucine]). After 20 days of tumour evolution, the animals underwent (18)-fludeoxyglucose positron emission computed tomography (F-18-FDG PET-CT) imaging, and after euthanasia, fresh tumour biopsy samples were taken for oxygen consumption rate measurements (Oroboros Oxygraph), electron microscopy analysis and RNA and protein extraction. Our main results from the LW group showed no tumour size change, lower tumour glucose (F-18-FDG) uptake, and reduced metastatic sites. Furthermore, leucine stimulated a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, higher mRNA and protein expression of oxidative phosphorylation components, and enhanced mitochondria! density/area even though the leucine-treated tumour had a higher number of apoptotic nuclei with increased oxidative stress. In summary, a leucine-rich diet directed Walker-256 tumour metabolism to a less glycolytic phenotype profile in which these metabolic alterations were associated with a decrease in tumour aggressiveness and reduction in the number of metastatic sites in rats fed a diet supplemented with this branched-chain amino acid.9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informação302863/2013-3; 302425/2016-92012/06955-0; 2014/13334-7; 2015/21890-0; 2017/02739-