Tryptophanol-derived oxazoloisoindolinone fluorescent probes for cellular localization studies of p53 activators.

The protein p53 is a transcription factor with several key roles in cells, including acting as a tumour suppressor. In most human cancers its tumour suppressor function is inactivated, either through inhibition by negative regulators or by mutation in the TP53 gene. Thus, there is a high interest in developing molecules able to activate p53 tumour suppressor activity. Tryptophanol-derived isoindolinones are known to act as wild-type and mutant p53 activators. Specifically, SLMP53-1 is a non-fluorescent wild-type and mutant p53 R280K reactivator, with potent in vivo anti-tumour activity in HCT116 and MDA-MB-231 mice xenograft models. With the aim of studying tryptophanol-derived isoindolinones intracellular localization by fluorescence microscopy, three SLMP53-1 based fluorescent probes were prepared. Here we report the design, synthesis, photophysical characterization, antiproliferative activity and cell localization studies of these fluorescent probes. The previously described structure-activity relationships of the SLMP53-1 scaffold set the basis for the design the fluorescent probes. The probes were prepared by connecting a small fluorophore (dansyl or 7-nitrobenzofurazan) to the indole nitrogen of the tryptophanol-derived oxazoloisoindolinone SLMP53-1 through two different linkers. The antiproliferative activity and cell localization studies of the three fluorescent probes were performed in HCT116 cells. The three probes showed enhanced internalization when compared with their fluorophore-linker intermediates, good photo-stability and high affinity for the endoplasmic reticulum, indicating the potential involvement of endoplasmic reticulum in the mechanism of action of tryptophanol-derived oxazoloisoindolinones.

Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells.

Lung cancer ranks as the predominant cause of cancer-related mortalities on a global scale. Despite progress in therapeutic interventions, encompassing surgical procedures, radiation, chemotherapy, targeted therapies and immunotherapy, the overall prognosis remains unfavorable. Imbalances in redox equilibrium and disrupted redox signaling, common traits in tumors, play crucial roles in malignant progression and treatment resistance. Cancer cells, often characterized by persistent high levels of reactive oxygen species (ROS) resulting from genetic, metabolic, and microenvironmental alterations, counterbalance this by enhancing their antioxidant capacity. Cysteine availability emerges as a critical factor in chemoresistance, shaping the survival dynamics of non-small cell lung cancer (NSCLC) cells. Selenium-chrysin (SeChry) was disclosed as a modulator of cysteine intracellular availability. This study comprehensively characterizes the metabolism of SeChry and investigates its cytotoxic effects in NSCLC. SeChry treatment induces notable metabolic shifts, particularly in selenocompound metabolism, impacting crucial pathways such as glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Additionally, SeChry affects the levels of key metabolites such as acetate, lactate, glucose, and amino acids, contributing to disruptions in redox homeostasis and cellular biosynthesis. The combination of SeChry with other treatments, such as glycolysis inhibition and chemotherapy, results in greater efficacy. Furthermore, by exploiting NSCLC's capacity to consume lactate, the use of lactic acid-conjugated dendrimer nanoparticles for SeChry delivery is investigated, showing specificity to cancer cells expressing monocarboxylate transporters.

Hospitais de Custódia e Tratamento Psiquiátrico no sistema prisional: a morte social decretada? / Custody and Psychiatric Treatment Hospitals in the prison system: A social death decreed?

Resumo Este texto apresenta uma discussão a respeito das pessoas com transtorno mental em conflito com a lei no Brasil e os Hospitais de Custódia e Tratamento Psiquiátrico, instituições inseridas no sistema prisional e consideradas híbridas entre a saúde e a justiça. Ao apresentarmos a realidade no contexto nacional, evidenciamos que a Reforma Psiquiátrica não alcançou essas instituições e esses indivíduos seguem estigmatizados, tendo os seus direitos humanos violados. Fundamentamos a necessidade de avançarmos o debate e trazemos alguns questionamentos na tentativa de fomentar a criação de novas saídas para o enfrentamento do problema, bem como a garantia de cuidado em saúde bem estruturado e baseado em evidências científicas.

Abstract This text discusses people with mental disorders in conflict with the law in Brazil and the Custody and Psychiatric Treatment Hospitals, institutions included in the prison system and considered a hybrid between health and justice. When we present the reality in the national context, we show that the Psychiatric Reform did not reach these institutions, and these individuals continue to be stigmatized, and their human rights are violated. We substantiate the need to advance the debate and raise some questions to establish new solutions to tackle the issue and ensure well-structured, scientific evidence-based health care.

Custody and Psychiatric Treatment Hospitals in the prison system: A social death decreed? / Hospitais de Custódia e Tratamento Psiquiátrico no sistema prisional: a morte social decretada?

This text discusses people with mental disorders in conflict with the law in Brazil and the Custody and Psychiatric Treatment Hospitals, institutions included in the prison system and considered a hybrid between health and justice. When we present the reality in the national context, we show that the Psychiatric Reform did not reach these institutions, and these individuals continue to be stigmatized, and their human rights are violated. We substantiate the need to advance the debate and raise some questions to establish new solutions to tackle the issue and ensure well-structured, scientific evidence-based health care.

Este texto apresenta uma discussão a respeito das pessoas com transtorno mental em conflito com a lei no Brasil e os Hospitais de Custódia e Tratamento Psiquiátrico, instituições inseridas no sistema prisional e consideradas híbridas entre a saúde e a justiça. Ao apresentarmos a realidade no contexto nacional, evidenciamos que a Reforma Psiquiátrica não alcançou essas instituições e esses indivíduos seguem estigmatizados, tendo os seus direitos humanos violados. Fundamentamos a necessidade de avançarmos o debate e trazemos alguns questionamentos na tentativa de fomentar a criação de novas saídas para o enfrentamento do problema, bem como a garantia de cuidado em saúde bem estruturado e baseado em evidências científicas.

Ginger: a systematic review of clinical trials and recent advances in encapsulation of its bioactive compounds.

Recently, the numbers of studies on natural products have considerably increased owing to their exceptional biological activities and health benefits. Their pharmacological attributes have played an immense role in detecting natural and safe alternative therapeutics, consequently extending their industrial applications. In this line, ginger (Zingiber officinale) has been gaining wide attention owing to its bioactive compounds, such as phenolic and terpene compounds. Ginger has a great pharmacological and biological potential in the prevention and treatment of various diseases, namely colds, nausea, arthritis, migraines and hypertension. However, these bioactive compounds are unstable and susceptible to degradation, volatilization and oxidation during extraction and processing, mainly owing to their exposure to environments with adverse conditions, such as high temperature, the presence of O2 and light. In this sense, this current review covers a wide range of topics, starting from the chemical profile and biological properties of ginger bioactive compounds (GBCs), their clinical effectiveness for the treatment of diseases and the application of different encapsulation methods (molecular inclusion, spray drying, complex coacervation, ionic strength and nanoemulsions) to protect and improve their application in food products. This work summarizes the fundamental principles of, recent progress in and effectiveness of different methods regarding the physicochemical, structural and functional properties of encapsulated GBCs. The potential use of encapsulated GBCs as a promising active ingredient to be applied in different food products is discussed in detail.

Nile Red Incubation Time Before Reading Fluorescence Greatly Influences the Yeast Neutral Lipids Quantification.

High-throughput screening methodologies to estimate lipid content in oleaginous yeasts use Nile red fluorescence in a given solvent and optimized excitation/emission wavelengths. However, Nile red fluorescence stabilization has been poorly analyzed, and high variability occurs when relative fluorescence is measured immediately or a few minutes after dye addition. The aim of this work was to analyze the fluorescence of Nile red at different incubation times using a variety of solvents and oleaginous/non-oleaginous yeast strains. We showed that fluorescence stabilization occurs between 20 and 30 min, depending on the strain and solvent. Therefore, we suggest that fluorescence measurements should be followed until stabilization, where Relative Fluorescence Units should be considered after stabilization for lipid content estimation.

The use of epifluorescence microscopy and fluorescent dyes for visualization of Oxyuris equi eggs.

This study presents a new method for visualization of Oxyuris equi eggs collected by means of a clear adhesive tape applied to the perianal region of horses. The obtained results indicate that this protocol permits a quick, easy, clear and selective visualization of Oxyuris equi eggs even in the presence of feces and other material. Another advantage of this method is that it can be used with fluorescent dyes solubilized in water, which will stain biologic material without dissolving or altering the adhesive tape and is also environmentally safe. Other dyes currently used for staining biologic materials use organic solvents, which may be combined with acids or bases in their formulation, preventing their use with the tape method.

A new methodology for the visualization of latent fingermarks on the sticky side of adhesive tapes using novel fluorescent dyes.

Three novel fluorescent dyes were evaluated for the detection of latent fingermarks on different types and colors of adhesive tapes. Compared with the conventional reagents used to reveal latent fingermarks on these surfaces, these new fluorescent dyes have many advantages. They are highly selective to fingermarks, require only a simple procedure, do not need pre- or post-treatment, have high thermal and photochemical stability, are low in cost and use only water as a solvent. In addition, the emitted fluorescence creates a sharp contrast with the fingermark surface, meaning the fingermarks can be clearly visualized and photographed when excited with longwave ultraviolet light (365nm).

Influência do fósforo na qualidade fisiológica de sementes de feijão comum armazenadas sob condições naturais / Phosphorus influence on physiological quality of common bean seeds stored under natural conditions

Com o objetivo de avaliar a influência do fósforo na qualidade fisiológica de sementes de feijão comum cultivado em solos de terras altas no Estado do Tocantins, realizou-se a pesquisa no Laboratório de Análise de Sementes da Universidade Federal do Tocantins - Campus Universitário de Gurupi com sementes de 19 genótipos de feijão comum cultivados em dois ambientes, um simulando condição de estresse de fósforo (20 kg ha-1) e o outro simulando condições ideais (120 kg ha-1). O delineamento experimental adotado foi a de blocos ao acaso, em esquema fatorial 19 x 2, sendo 19 genótipos e dois níveis de fósforo, com quatro repetições, sendo esses dados analisados por meio do teste Scott-Knott e Tukey, com 5% de probabilidade. A qualidade fisiológica das sementes de feijão comum foi realizada por meios dos testes padrão de germinação, primeira contagem, tetrazólio e massa de mil sementes. Entre os cultivares houve desempenho diferenciado quanto à qualidade fisiológica de sementes de feijão; para os cultivares IACGalante, IAC-Carioca Eté, IAC-Una, IPR-Juriti, IPR-Colibri, IPR-Siriri, IPR-139, IPR-Gralha, IPR-Tiziu, IPR-Chopim e IPR-Corujinha o incremento de fósforo não resultou em melhoria na qualidade fisiológica das sementes produzidas; e os genótipos IAC-Carioca Tybatã, IAC-Carioca Eté e Tangará produziram sementes de melhor qualidade fisiológica.

In order to evaluate the phosphorus influence over physiological quality of common bean seeds grown on upland soil in Estate of Tocantins, help research was carried out on the Seed Analysis Laboratory of Universidade Federal do Tocantins- Campus of Gurupi with seeds of Nineteen bean genotypes tested. They were grown in two environments, one simulating condition of phosphorus stress (20 kg ha-1) and another one simulating ideal conditions (120 kg ha-1). The experimental design adopted was the completely randomized blocs in a factorial scheme 19x2, being 19 genotypes and 2 levels of phosphorus, with four replications. The data was analyzed and applied the Scott-Knott and Tukey tests, both with 5% of probability. The physiological quality of common bean was analyzed through the standard germination test, first count, tetrazolium test and one thousand grains mass. Among the cultivars there was a differentiated physiological quality of bean seeds; for cultivars IAC-Galante, IAC-Carioca Eté, IAC-Una, IPR-Juriti, IPR-Colibri, IPRSiriri, IPR-139, IPR-Gralha, IPR-Tiziu, IPR-Chopim and IPR-Corujinha, the increases in the level of phosphorus did not result on better physiological quality of the produced seeds; and the genotypes IAC-Carioca Tybatã, IAC-Carioca Eté and Tangará produced seeds of better physiological quality.

Danos e sintomatologia de vírus associado à cultura da melancia no estado do Tocantins / Damage and symptoms associated with watermelon virus in Tocantins state

A baixa produtividade e a qualidade dos frutos de melancia estão quase sempre associadas à ocorrência de fitopatogenos, dentre estes destacam as doenças de etiologia viral. Visando o entendimento do complexo vírus/planta de melancia, este trabalho teve o objetivo de avaliar os danos e sintomas induzidos pelos vírus PRSV-W, CMV, ZYMV e WMV, quando inoculados em plantas de melancia, cv. 'Crimson sweet', aos 5, 12 e 19 dias após a emergência (DAE). Os vírus PRSV-W, CMV, ZYMV e WMV influenciaram significativamente (p<0,05) na redução do peso da matéria fresca da parte aérea, na coloração da polpa e redução no peso dos frutos da melancia. Assim como, no teor de sólidos solúveis (ºBrix). Sendo mais significativa em plantas inoculadas com CMV. De modo geral, os vírus PRSV-W, WMV, CMV e ZYMV afetaram o desenvolvimento, a produção da planta da melancia e consequentemente, limita a qualidade do fruto.

Watermelon is one of the most important vegetables grown in Brazil. However, there are several factors responsible for low productivity of crops. Among these stands out the occurrence of associated virus culture. Thus, this study aimed to assess the damage and symptoms of PRSV-W, CMV, ZYMV and WMV inoculated at 5, 12 and 19 days after emergence (DAE). According to the results, PRSV-W viruses, CMV, ZYMV and WMV influenced significantly (p <0.05) reduction in the fresh weight of shoots and on pulp and reduction of fruit weight of inoculated plants. As noted on pulp plants inoculated with PRSV-W, at 5 DAE. With regard to the soluble solids content (° Brix) was dramatically reduced by the virus and inoculation period, in this case being more significant fruits of plants inoculated with CMV presented Brix 3.67 to 5.11 depending on the inoculation period. In general, viruses PRSV-W, WMV, CMV, ZYMV and influence the development and consequently the production of watermelon. Thus, an important factor for the reduction in the quality of fruit produced.

Seleção precoce e fenotipagem de linhagens de milho quanto à arquitetura das raízes seminais / Early selection and phenotiping of line of corn as for the architecture of the seminal roots

Objetivou-se selecionar e fenotipar linhagens de milho quanto à arquitetura das raízes seminais em relação à raiz primária da planta. Foram avaliadas 20 linhagens de milho em solução nutritiva, em experimento disposto no delineamento de blocos casualizados, com três repetições. Foram realizadas medições de crescimento das raízes e dos ângulos das raízes seminais. Os pêlos radiculares foram avaliados visualmente. Os resultados mostraram que as linhagens apresentaram diferenças significativas quanto ao crescimento das raízes primárias e seminal, ângulos das raízes seminais e de pêlos radiculares, não obtendo diferença apenas para número de raízes seminais. A linhagem de milho L11 foi a que apresentou maior densidade de pêlos radiculares, ângulos e crescimento de raízes seminais. Conclui-se que as linhagens de milho L11 e L14 têm os maiores ângulos das raízes seminais; as linhagens L15 e L17 têm as maiores densidades de pêlos radiculares; a linhagem L11 sobressaiu com maior número de raízes seminais.

The objective was to select and fhenotiping corn line on the seminal roots architecture in relation to the primary root of the plant. They were appraised 20 corn lines in nutrient solution in experiment provisions of randomized block design with three replications. Were measured growth of the roots and the angles of the seminal roots. The root hairs were visually assessed. The results showed that the strains exhibited significant differences in root growth and angles seminal roots and root hairs, getting no difference only for the number of seminal roots. The corn line L11 showed the highest density of root hairs, angles and growth of seminal roots. It is concluded that corn lines L11 and L14 have the highest angles of seminal roots; lines L15 and L17 have the highest density of root hairs, the L11 excelled with the largest number of seminal roots.

Eficiência quanto ao uso e resposta à aplicação de nitrogênio de cultivares de arroz em solos de terras altas no sul do estado de Tocantins, SAFRA 2007/2008p / Efficiency in the use and application of nitrogen from rice cultivars in highland soils in the southern state of Tocantins, SAFRA 2007/2008

Objetivou-se com este trabalho estudar a eficiência e resposta quanto ao uso de nitrogênio de cultivares de arroz em solos de terras altas no sul do Estado de Tocantins. Os tratamentos envolveram seis cultivares comerciais de arroz (BRS-Bonança BRS-Caiapó, BRS-Sertaneja, BRSMG-Curinga, BRSMG-Conai e BRS-Primavera), que foram cultivadas em dois ambientes distintos. Para simular ambientes com baixo e alto nível de nitrogênio, foram utilizadas as doses 20 e 120 kg ha-1 de nitrogênio, respectivamente. O delineamento experimental utilizado foi o de blocos casualizados, com quatro repetições. Através da produtividade de grãos, classificou-se as cultivares quanto à eficiência no uso e resposta a aplicação de nitrogênio. Não foram identificadas cultivares consideradas eficientes e responsivas a aplicação de nitrogênio. As cultivares BRS-Bonança, BRS-Caiapó e BRS-Primavera mostraram-se eficientes e não responsivas à aplicação de nitrogênio.

This research's objective was to study the efficiency in the usage of nitrogen in rice cultivars on high land in the south of Tocantins State. The experiments involved sex commercial cultivars of rice (BRS-Bonança BRSCaiapó, BRS-Sertaneja, BRSMG-Curinga, BRSMG-Conai and BRS-Primavera), which were farmed in two distinct environments. In order to stimulate areas with high and low nitrogen levels, there were used doses of 20 and 120 kg ha-1 of P2O5 respectively. The experiments were carried out in a completely randomized blocks design, with four replicates. Throughout production the grain's productivity was classified as efficient cultivars in respect to the application and response of nitrogen. Did not identify efficient cultivars in response to the usage of nitrogen. The cultivars BRS-Bonança, BRS-Caiapó and BRS-Primavera demonstrated efficiencies in the use of nitrogen and no responsive to its application.

Influência de diferentes épocas de semeadura no desempenho agronômico de cultivares de girassol no cerrado tocantinense / Influence of different times of sowing on the agronomic performance of sunflower cultivars in cerrado tocantinense

A cultura do girassol (Helianthus annuus L.) pode ser conduzida em diferentes épocas de semeadura durante o ano agrícola, destacando-se entre as culturas viáveis a serem exploradas no Estado do Tocantins, nas regiões de cerrado. Entretanto, os cultivares podem apresentar diferenças de adaptação e desenvolvimento, dependendo da localidade e época de semeadura. O objetivo deste trabalho foi avaliar o desempenho de cultivares de girassol em diferentes épocas de semeadura no Sul do Estado do Tocantins. O experimento foi instalado em Gurupi-TO, safra 2008/2009 em quatro épocas de semeadura. O delineamento experimental utilizado foi em blocos casualizados, com 20 tratamentos e três repetições. Os tratamentos foram dispostos num esquema fatorial 4 x 5, constituído por quatro épocas de semeadura EP1 (24/11/2008), EP2 (01/12/2008), EP3 (18/12/2008) e EP4 (30/12/2008) e cinco cultivares H250, H251, H358, H360, e H884. Verificou-se interação significativa entre épocas de semeadura e cultivares para as características: florescimento, altura de planta, porcentagem de aquênios normais, peso hectolitro e produtividade de aquênios. Houve influência negativa para todas as características avaliadas à medida que as semeaduras foram retardadas, em decorrência, provavelmente, da incidência do patógeno Alternaria helianthi. Com a semeadura antecipada para o inicio do período chuvoso (EP1) foi possível ter uma produtividade acima de 2300 até 3000 kg ha-1, dependendo da cultivar. E o cultivar que mais se destacou foi H251 na EP1.

The crop of sunflower (Helianthus annuus L.) can be conducted at different sowing times during the growing season, standing out among the viable crops to be explored in the state of Tocantins, in the cerrado regions. However, cultivars may show adaptation and development differently depending on the place and sowing time. The objective of this study was to evaluate the performance of sunflower cultivars in different sowing dates in the southern state of Tocantins. The experiment was installed in Gurupi-TO, at 2008/2009 growing season 2008/2009 in four sowing times. The experimental design was randomized blocks with 20 treatments and three repetitions. The treatments were disposed in a 4 x 5 factorial, constituted by four sowing times EP1 (24/11/2008), EP2 (01/12/2008), EP3 (18/12/2008) and EP4 (30/12/2008) and five cultivars H250, H251, H358, H360, and H884. Significant interaction was verified between sowing times and cultivars for characteristics: flowering, plant height, porcentage normal achene, hectolitre weight and productivity of achenes. There was negative influence for all avaluated characteristics as the sowings were delayed, in consequence, probably, of the incidence of pathogen Alternaria helianthi. With early sowing to the beginning of the rainy period (EP1) was possible to have a yield of 2300 up to 3000 kg há-1 , depending of the cultivar. And the cultivar one that stood out was the H251 in EP1.

Olanzapine for recurrent excessive irritability and psychotic symptoms after mesial temporal lobectomy in a patient with temporal lobe epilepsy.

We report the case of a patient with temporal lobe epilepsy, nonresponsive to antiepileptic drugs, who became seizure-free, but developed recurrent excessive irritability and psychotic symptoms after successful mesial temporal lobectomy. This patient was refractory to various pharmacological treatments including antipsychotics, mood stabilizers, and benzodiazepines before being successfully treated with olanzapine.

Demência de Alzheimer: correlação entre memória e autonomia / Alzheimer disease: correlation between memory and autonomy

Discute-se neste artigo de revisão a relação entre demência e autonomia, com enfoque particular nas perdas cognitivas e no comprometimento da memória. A doença de Alzheimer (DA) é uma doença neurodegenerativa progressiva que provoca demência, comprometendo, ao longo de sua lenta evolução, a autonomia dos pacientes. A redução da autonomia é o fator determinante da dependência de um cuidador, que se torna indispensável para preservar o provimento das necessidades básicas da vida diária do paciente. É feita uma distinção entre a dependência por limitações motoras e redução de mobilidade, daquela decorrente das perdas cognitivas. Discute-se também a importância do uso racional dos instrumentos de rastreio cognitivo e avaliação funcional na mensuração do grau de autonomia dos indivíduos acometidos.