Immunometabolism in cancer: A journey into innate and adaptive cells.

In recent years, mostly spanning the past decade, the concept of immunometabolism has ushered with a novel perspective on carcinogenesis, tumor progression, and tumor response to therapy. It has become clear that the metabolic state of immune cells plays a significant role in shaping their antitumor or protumor activities within the cancer microenvironment. Consequently, the examination of tumor metabolic heterogeneity, including an exploration of immunometabolism, proves indispensable for enhancing prognostic tools and advancing the quest for personalized treatments. Here we have delved into how metabolic reprogramming profoundly influences the acquisition and maintenance of functional states, spanning from effector and cytotoxic profiles to regulatory and immunosuppressive phenotypes in both innate and adaptive immunity. These alterations wield considerable influence over tumor evolution and affect the outcome of cancer. Furthermore, we explore some of the cellular signaling mechanisms that underpin the metabolic and phenotypic flexibility of immune cells in response to external stimuli.

Diclofenac sodium adsorption on activated carbon: experimental, modeling and bayesian statistics.

The present study modeled the adsorption process of the drug diclofenac sodium on activated charcoal. For this purpose, a mass balance-based model was used considering a fixed bed column. The mass transfer rate in the solid phase was represented by a driving force model proposed in this study, and a gamma exponent with a range of 0 > γ ≤ 2 was assigned to the model. Different isotherms were adopted to represent the equilibrium at the solid/liquid interface: the Langmuir, Freundlich, Sips and Redlich-Peterson isotherms. The modeling was approached from the perspective of Bayesian statistics, and the Markov chain Monte Carlo method was used for parameter estimation. Model validation was performed with experimental data obtained under different operating conditions of initial concentration ($C_{0.

Armed violence in Manguinhos/RJ, Brazil: health and daily life of health and education workers. / Violência armada em Manguinhos/RJ, Brasil: saúde e cotidiano de trabalhadoras(es) de saúde e educação.

The article presents the results of qualitative action research on armed violence with health and education professionals and territorial community services in Manguinhos, Rio de Janeiro, Brazil. It is justified by the urgent nature of this violence in the territory and aims to identify its impacts on their health and work, coping, protection, and care strategies. The effects of armed violence on health and education professionals and the territory are discussed through interviews and focus groups with participant observation, identifying some of its transversalities, such as the Brazilian State racist public security policy based on a warlike logic of confrontation with groups with armed control of the territory, which makes life precarious by exposing residents and workers to constant risks, weakening the community fabric and preventing full access to health and education.

O artigo apresenta resultados de uma pesquisa qualitativa sobre violência armada, do tipo pesquisa-ação, com profissionais de saúde e de educação e serviços comunitários territoriais em Manguinhos/RJ. Justifica-se pela premência dessa violência no território, tendo como objetivo identificar seus impactos na saúde e no trabalho, assim como as estratégias de enfrentamento, proteção e cuidado empreendidas. A partir de entrevistas e grupos focais com profissionais de saúde e da educação e observação participante, discutem-se os efeitos da violência armada sobre elas(es) e o território, identificando algumas de suas transversalidades, como a política de segurança pública racista empreendida pelo Estado brasileiro, baseada numa lógica bélica de confronto com grupos que têm domínio armado de território, que precariza a vida ao expor moradoras(es) e trabalhadoras(es) a riscos constantes, enfraquece o tecido comunitário e impede o pleno acesso à saúde e à educação.

Stroke related sarcopenia in individuals with different physical activity levels: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Individuals after stroke are likely to deal with the possible development of sarcopenia and reduced physical activity levels. The purpose of this study was to compare sarcopenia of individuals with chronic stroke who were stratified according to their physical activity levels, and to evaluate the relationship between sarcopenia and physical activity levels. MATERIALS AND METHODS: This cross-sectional study was conducted with individuals after chronic stroke recruited from the general community. Individuals were submitted to sarcopenia screening (SARC-F questionnaire) and assessment of physical activity levels (Human Activity Profile questionnaire) to classify the individuals as impaired, moderately active, and active according to their Adjusted Activity Status (AAS). ANOVA was used to investigate the sarcopenia between groups and Pearson's coefficient to investigate the association among variables. RESULTS: Fifty-four individuals with a mean age of 56 ± 17.4 years were included. Twenty-one percent of the individuals were screened for sarcopenia. Inactive individuals had higher mean scores in the SARC-F (3.6 ± 2.1 points), whereas moderately active and active individuals presented lower mean scores in the same questionnaire, being 1.2 ± 1.1 points and 0.5 ± 0.7 points, respectively. A statistically significant inverse and high association was found between sarcopenia and physical activity levels (r = -0.716; p < 0.01). CONCLUSION: Sarcopenia was found to be higher in individuals after chronic stroke with lower physical activity levels considered inactive when compared to individuals with higher physical activity levels. Furthermore, there was an inverse relationship between sarcopenia and physical activity level in stroke survivors.

Investigation of co-treatment multi-targeting approaches in breast cancer cell lines.

In 2020, breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer in the world. Tumor microenvironment (TME) plays a critical role in resistance to standard therapies and tumor progression. Two key factors within the TME include adenosine, an immunosuppressive molecule, and glucose, which serves as the primary energy source for tumor cells. In this scenario, inhibiting the purinergic pathway and glucose uptake might be a promising strategy. Therefore, we sought to evaluated different treatment approaches in BC cells (Dapagliflozin, a SGLT2 inhibitor; Paclitaxel, the standard chemotherapy for BC; and ARL67156/APCP, inhibitors of CD39 and CD73, respectively). The expression of some membrane markers relevant to resistance was assessed. BC cell-lines (MCF-7 and MDA-MB-231) were co-treated and cell viability, cell cycle, and annexin/PI assays were performed. Our analysis showed promising results, where the combination of these compounds led to cell death by apoptosis/necrosis and cell cycle arrest. Dapagliflozin showed more impact on early apoptosis, whereas Paclitaxel led to late apoptosis/necrosis as the main mechanism of cell death. Inhibiting purinergic signaling also contributed to reducing cell viability together with the other drugs, suggesting it could have an influence on breast cancer survival mechanisms. Indeed, the overexpression of the NT5E gene in patients with ER+ tumors is strongly associated with reduced overall survival and progression-free interval. However, more studies are needed to fully understand the interactions and mechanism underlying these co-treatment multi-targeting approaches.

Characterization of purinergic signaling in tumor-infiltrating lymphocytes from lower- and high-grade gliomas.

Malignant gliomas are highly heterogeneous glia-derived tumors that present an aggressive and invasive nature, with a dismal prognosis. The multi-dimensional interactions between glioma cells and other tumor microenvironment (TME) non-tumoral components constitute a challenge to finding successful treatment strategies. Several molecules, such as extracellular purines, participate in signaling events and support the immunosuppressive TME of glioma patients. The purinergic signaling and the ectoenzymes network involved in the metabolism of these extracellular nucleotides are still unexplored in the glioma TME, especially in lower-grade gliomas (LGG). Also, differences between IDH-mutant (IDH-Mut) versus wild-type (IDH-WT) gliomas are still unknown in this context. For the first time, to our knowledge, this study characterizes the TME of LGG, high-grade gliomas (HGG) IDH-Mut, and HGG IDH-WT patients regarding purinergic ectoenzymes and P1 receptors, focusing on tumor-infiltrating lymphocytes. Here, we show that ectoenzymes from both canonical and non-canonical pathways are increased in the TME when compared to the peripheral blood. We hypothesize this enhancement supports extracellular adenosine generation, hence increasing TME immunosuppression.

Violência armada em Manguinhos/RJ, Brasil: saúde e cotidiano de trabalhadoras(es) de saúde e educação / Armed violence in Manguinhos/RJ, Brazil: health and daily life of health and education workers

Resumo O artigo apresenta resultados de uma pesquisa qualitativa sobre violência armada, do tipo pesquisa-ação, com profissionais de saúde e de educação e serviços comunitários territoriais em Manguinhos/RJ. Justifica-se pela premência dessa violência no território, tendo como objetivo identificar seus impactos na saúde e no trabalho, assim como as estratégias de enfrentamento, proteção e cuidado empreendidas. A partir de entrevistas e grupos focais com profissionais de saúde e da educação e observação participante, discutem-se os efeitos da violência armada sobre elas(es) e o território, identificando algumas de suas transversalidades, como a política de segurança pública racista empreendida pelo Estado brasileiro, baseada numa lógica bélica de confronto com grupos que têm domínio armado de território, que precariza a vida ao expor moradoras(es) e trabalhadoras(es) a riscos constantes, enfraquece o tecido comunitário e impede o pleno acesso à saúde e à educação.

Abstract The article presents the results of qualitative action research on armed violence with health and education professionals and territorial community services in Manguinhos, Rio de Janeiro, Brazil. It is justified by the urgent nature of this violence in the territory and aims to identify its impacts on their health and work, coping, protection, and care strategies. The effects of armed violence on health and education professionals and the territory are discussed through interviews and focus groups with participant observation, identifying some of its transversalities, such as the Brazilian State racist public security policy based on a warlike logic of confrontation with groups with armed control of the territory, which makes life precarious by exposing residents and workers to constant risks, weakening the community fabric and preventing full access to health and education.

Migração, trabalho e violência: interfaces com a Saúde / Migration labor and violence: interfaces with healthcare / Migración trabajo y violencia: interfaces con la salud

A cartilha é um material educativo fruto da pesquisa "Migração, saúde e violências: experiências de trabalhadoras(es) migrantes e refugiadas(os) no Rio de Janeiro", durante a qual foram escutadas(os) migrantes e refugiadas(os) residentes no Brasil, especificamente no estado do Rio de Janeiro. Os deslocamentos humanos são uma realidade de dimensões globais e garantir o acesso e a permanência de migrantes e refugiadas(os) em postos de trabalho seguros, saudáveis e não violentos deve ser uma das finalidades de sociedades que prezam pela justiça social. A migração e o refúgio podem trazer mudanças na forma de organização familiar e a necessidade de buscar emprego, casa, estudo, relações de amizade e redes de apoio. Ao mesmo tempo em que a migração e o refúgio podem ser experiências que tragam novos recomeços, os sentimentos de incerteza, insegurança, medo, saudades e preocupação estão presentes no cotidiano de migrantes e refugiadas(os) e se expressam também na esfera do trabalho. Associado a isso, o mundo do trabalho tem passado por profundas transformações, principalmente nas últimas cinco décadas, que vêm impactando a vida de trabalhadoras(es), como o aumento do desemprego, contratações temporárias, baixos salários e a permanência de trabalho escravizado e forçado. Portanto, é preciso reconhecê-las para enfrentá-las, de modo a garantir um ambiente de trabalho seguro e saudável para todas(os). (AU)

Validation of the Duke Activity Status Index questionnaire by telephone In individuals after stroke.

Background: Due to social restrictions caused by the pandemic, there was a need to validate outcome measures that could be administered by telephone call. Administration by telephone allows to remotely follow up stroke survivors since most of them have mobility restrictions. This study aims to investigate the validity of the Duke Activity Status Index (DASI) questionnaire administration to chronic stroke survivors through telephone call. Methods: This is a cross-sectional study, developed according to COSMIN and GRRAS recommendations. It was recruited chronic stroke survivors, who answered the DASI questionnaire in two different time-points, in person and after a period of 5-7 days through a telephone call. Results: Out of 260 subjects, 50 individuals (52% women) with a mean age of 56 ± 17 years were included. No statistically significant differences were observed (MD = -0.88; SD:4.14; 95% CI, -2.06 to 0.28; p = 0.13) on the total score of DASI administered in person and by telephone call. There was a very high agreement between the administration modes (ICC - 0.99; 95% CI, 0.94-0.98; p < 0.05). The Kappa coefficient ranged from 0.390 to 1.000, with the first item showing the best agreement (k = 1.000) and the fourth showing the worst agreement (k = 0.390). Conclusions: The DASI questionnaire is valid to assess functional capacity and can be administered through telephone in chronic stroke survivors. Thus, clinicians and researchers may decide to avoid patient transportations administering DASI through telephone call, as a reliable measure for stroke survivors.

Utilização do diamino fluoreto de prata como estratégia para tratamento da cárie na primeira infância em paciente não colaborador: relato de caso / Use of silver diamine fluoride as a strategy for treating early childhood caries in a non-cooperative patient: case report

Objetivo: relatar o uso do diamino fluoreto de prata (DFP) para tratamento da cárie na primeira infância em paciente não colaboradora de 3 anos. Relato do caso: ao exame clínico inicial, realizado com auxílio da estabilização protetora, notou-se que a paciente estava na fase de dentição decídua, possuía excessivo acúmulo de biofilme visível, sem sensibilidade ou qualquer outro sintoma, porém apresentando múltiplas lesões de cárie ativas em todos os dentes, exceto nos incisivos inferiores. Optou-se pelo uso do DFP 30% (Cariestop®) para o tratamento das lesões de cárie e também como alternativa para o manejo do comportamento, que foi classificado usando a Escala Comportamental de Frankl. Já na consulta inicial foi realizada a primeira aplicação, durante 2 minutos, diretamente sobre as lesões cavitadas em dentina dos dentes do hemiarco superior esquerdo, após profilaxia dentária prévia. Na segunda consulta, foi realizada a aplicação do produto nas lesões do hemiarco superior direito, enquanto no terceiro atendimento foi aplicado o DFP nos molares e caninos inferiores. Em todas as consultas foi realizada instrução de higiene bucal e de dieta com a responsável. Resultados: no decorrer do tratamento a paciente apresentou expressiva melhora no comportamento, que havia sido definitivamente negativo na primeira consulta. Ela sentou-se sozinha na cadeira e não precisou da estabilização protetora na última consulta, apresentando comportamento positivo. Verificou-se também a paralisação das lesões de cárie em decorrência do uso do DFP. Conclusão: o uso de DFP para tratamento de lesões cavitadas de cárie em pacientes não colaboradores foi considerado uma estratégia eficaz tanto para paralisação das lesões quanto para auxílio no condicionamento do comportamento.

Objective: to report the use of silver diamine fluoride (SDF) for the treatment of caries in early childhood in a 3-year-old non-collaborating patient. Case report: at the initial clinical examination, performed with protective stabilization, it was verified that the patient was in the primary dentition period, had excessive accumulation of visible biofilm, no dental sensibility or any other symptom, but had multiple active caries lesions in all teeth except the lower incisors. It was decided to use SDF 30% (Cariestop®) for the treatment of caries lesions and also as an alternative for managing behavior, which was classified using the Frankl Behavioral Scale. In the initial consultation, the first application was performed, for 2 minutes, directly on the dentin cavitated lesions of the teeth of the upper left hemiarch, after previous dental prophylaxis. In the second appointment, the product was applied into the lesions on the upper right hemiarch, while in the third visit, the SDF was applied to the lower molars and canines. In all consultations, instructions on oral hygiene and diet were given to the guardian. Results: during the treatment, the patient showed a significant improvement in behavior, which had been definitely negative in the first consultation. She sat alone in the dental chair and did not need protective stabilization at her last visit, showing positive behavior. There was also an arrest of carious lesions due to the use of DFP. Conclusion: The use of SDF for the treatment of cavitated carious lesions in non- collaborating patients was considered an effective strategy both for arresting the lesions and for improving the condition behavior.

Dispersion and persistence of antimicrobial resistance genes among Staphylococcus spp. and Mammaliicoccus spp. isolated along a swine manure treatment plant.

Staphylococcus spp. and Mammaliicoccus spp. colonize the skin and mucosa of humans and other animals and are responsible for several opportunistic infections. Staphylococci antibiotic resistance may be present in the environment due to the spread of treated and untreated manure from the livestock industry due to antibiotic use to disease control or growth promoter. In this work, we analyzed the species distribution and antimicrobial susceptibility of Staphylococcus and Mammaliicoccus species along different sites of a swine manure treatment plant from Southeastern Brazil. Bacterial colonies were obtained on mannitol salt agar, selected after catalase test and Gram staining, and finally identified by mass spectrometry and sequencing of the tuf gene. According to the results, S.cohnii and S. simulans were the most prevalent species. Antibiotic resistance test revealed that several strains were resistant to multiple drugs, with high levels of chloramphenicol resistance (98%), followed by erythromycin (79%), tetracycline (73%), gentamicin (46%), ciprofloxacin (42%), cefoxitin (18%), sulfamethoxazole + trimethoprim (12%), and linezolid (4%). In addition, gene detection by PCR showed that all strains carried at least 2 resistance genes and one of them carried all 11 genes investigated. Using the GTG5-PCR approach, a high genetic similarity was observed between some strains that were isolated from different points of the treatment plant. Although some were seemingly identical, differences in their resistance phenotype and genotype suggest horizontal gene transfer. The presence of resistant bacteria and resistance genes along the treatment system highlights the potential risk of contamination by people in direct contact with these animals and the soil since the effluent is used as a biofertilizer in the surrounding environment.

Hydraulic conductivity and native embolism of Geneva® Series apple rootstocks measured by the XYL'EM-Plus® embolism meter

Most commercial apple orchards are established on either Marubakaido (Malus prunifolia Borkh.) (high vigor), M-9 (Malus pumila) (low vigor), or a combination of both rootstocks through the intergrafting technique. The Geneva® Series rootstocks were developed as an alternative to orchards modernization. The vigor of rootstocks influences the anatomical xylem formation and, therefore, the canopy cultivar's hydraulic conductivity. When affected by embolism, hydraulic conductivity harms plant metabolism, reducing crop yield and fruit quality. This study aimed to evaluate four Geneva® Series rootstocks with potential use in southern Brazil, in terms of hydraulic conductivity (K) and percentage loss of conductance (PLC), during the winter period in two different years. The G.213 rootstock presented the best performance for the variables analyzed; however, higher values of xylem functionality loss were observed in G.814.

Lymphocytes from B-acute lymphoblastic leukemia patients present differential regulation of the adenosinergic axis depending on risk stratification.

PURPOSE: Although risk-stratified chemotherapy regimens improve B-cell acute lymphoblastic leukemia (B-ALL) clinical outcome, relapse occurs in a significant number of cases. The identification of new therapeutic targets as well as prognostic and diagnostic biomarkers can improve B-ALL patients' clinical outcomes. Purinergic signaling is an important pathway in cancer progression, however the expression of ectonucleotidases and their impact on immune cells in B-ALL lacks exploration. We aimed to analyze the expression of ectonucleotidases in B-ALL patients' lymphocyte subpopulations. METHODS: Peripheral blood samples from 15 patients diagnosed with B-ALL were analyzed. Flow cytometry was used to analyze cellularity, expression level of CD38, CD39, and CD73, and frequency of [Formula: see text], and [Formula: see text] in lymphocyte subpopulations. Plasma was used for cytokines (by CBA kit) and adenine nucleosides/nucleotides detection (by HPLC). RESULTS: Comparing B-ALL patients to health donors, we observed an increase of CD4 + and CD8 + T-cells. In addition, a decrease in CD38 expression in B and Treg subpopulations and an increase in CD39+ CD73+ frequency in Breg and CD8+ T-cells. Analyzing cytokines and adenine nucleosides/nucleotides, we found a decrease in TNF, IL-1ß, and ADO concentrations, together with an increase in AMP in B-ALL patients' plasma. CONCLUSION: As immunomodulators, the expression of ectonucleotidases might be associated with activation states, as well as the abundance of different cellular subsets. We observed a pro-tumor immunity expression profile in B-ALL patients at diagnosis, being associated with cell exhaustion and immune evasion in B-ALL.

Modelo explicativo de não adesão ao paradigma psicossocial da saúde mental / Explanatory model of non-adhesion to the psychosocial mental health paradigm / Modelo explicativo de la no adhesión al paradigma psicosocial de la salud mental

Este estudo teve como objetivo propor um modelo explicativo de não adesão ao paradigma psicossocial da saúde mental a partir dos estereótipos, das crenças sobre a etiologia da doença mental, da percepção de ameaça e do preconceito. Para tanto, contou-se com a participação de 400 universitários, com média de idade de 24,64 anos (DP = 6, 64), sendo a maioria do sexo feminino (75,6%). Para a proposição do modelo, foi realizada uma path analysis. O modelo proposto demonstrou que quanto maior a percepção de ameaça e a concordância com o estereótipo de incapacidade, menor o apoio ao paradigma psicossocial. Ademais, verificou-se que as crenças acerca da etiologia da doença mental e os estereótipos estão na base da percepção de ameaça e todas essas variáveis juntas predizem maior preconceito. Os achados desta pesquisa fornecem subsídios científicos para a realização de intervenções eficazes e consistentes que fortaleçam o paradigma psicossocial no cenário nacional. (AU)

This study aimed to propose an explanatory model of non-adherence to the psychosocial paradigm of mental health based on stereotypes, beliefs about the etiology of mental illness, perception of threat, and prejudice. Participants included a total of 400 university students, with a mean age of 24.64 years (SD = 6, 64), mostly women (75.6%). A path analysis was performed to propose the model, which showed that the greater the perception of threat and the agreement with the disability stereotype, the lower the support for the psychosocial paradigm. Furthermore, it was found that beliefs about the etiology of mental illness and stereotypes are at the basis of the perception of threat and all these variables together predict greater prejudice. The findings of this research provide scientific support for effective and consistent interventions that strengthen the psychosocial paradigm on the national scene. (AU)

Este estudio tuvo como objetivo proponer un modelo explicativo de la no adherencia al paradigma psicosocial de la salud mental basado en estereotipos, creencias sobre la etiología de la enfermedad mental, percepción de amenaza y prejuicio. Para ello participaron 400 estudiantes universitarios, con una edad media de 24,64 años (DS = 6,64), siendo la mayoría mujeres (75,6 %). Para la proposición del modelo, se realizó un path análisis. El modelo sugerido demostró que, a mayor percepción de amenaza y concordancia con el estereotipo de discapacidad, menor apoyo al paradigma psicosocial. Además, se encontró que las creencias sobre la etiología de la enfermedad mental y los estereotipos están en la base de la percepción de amenaza y todas estas variables en conjunto predicen un mayor prejuicio. Los hallazgos de esta investigación brindan soporte científico para ejecutar intervenciones efectivas y consistentes que fortalezcan el paradigma psicosocial en el escenario nacional. (AU)

Tumor necrosis factor alpha (TNF-α) blockage reduces acute inflammation and delayed wound healing in oral ulcer of rats.

Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.1 mL/kg of saline) and five groups treated with anti-TNF-α infliximab (INF) at 1, 3, 5, 7, and 10 mg/kg immediately before OTU production. The animals were weighed (day 0) and euthanized on days 1, 3, 7, 14 and 21 after ulceration. The ulcers were clinically measured, and the mucosa samples were histologically (scores 0-4), histochemically (collagen assay (pircrosirius)), histomorphometrically (cell counting), and immunohistochemically (TNF-α, α-smooth-muscle-actin (α-SMA), monocyte-chemoattractive-protein-1 (MCP-1), interleukin-8 (IL-8), and fibroblast-growth-factor (FGF)) analyzed. The Evans blue assay was used to measure the vascular permeability. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). High doses of INF reduced the OTU area (p = 0.043), body mass loss (p = 0.023), vascular permeability (p < 0.001), and reduced delayed histologic scores (p < 0.05), polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, blood vessel counting (p = 0.006), and total (p < 0.001), type-I (p = 0.018), and type-III (p < 0.001) collagen. INF treatment reduced TNF-α immunostaining and delayed MPC-1, FGF, and α-SMA expression, with little/none influence in IL-8 immunostaining. TNF-α blockage by INF reduced acute inflammation in OTU but delayed cell migration and wound healing.

Caveolin-1 influences mitochondrial plasticity and function in hepatic stellate cell activation.

Caveolin-1 (Cav-1) is an integral membrane protein present in all organelles, responsible for regulating and integrating multiple signals as a platform. Mitochondria are extremely adaptable to external cues in chronic liver diseases, and expression of Cav-1 may affect mitochondrial flexibility in hepatic stellate cells (HSCs) activation. We previously demonstrated that exogenous expression of Cav-1 was sufficient to increase some classical markers of activation in HSCs. Here, we aimed to evaluate the influence of exogenous expression and knockdown of Cav-1 on regulating the mitochondrial plasticity, metabolism, endoplasmic reticulum (ER)-mitochondria distance, and lysosomal activity in HSCs. To characterize the mitochondrial, lysosomal morphology, and ER-mitochondria distance, we perform transmission electron microscope analysis. We accessed mitochondria and lysosomal networks and functions through a confocal microscope and flow cytometry. The expression of mitochondrial machinery fusion/fission genes was examined by real-time polymerase chain reaction. Total and mitochondrial cholesterol content was measured using Amplex Red. To define energy metabolism, we used the Oroboros system in the cells. We report that GRX cells with exogenous expression or knockdown of Cav-1 changed mitochondrial morphometric parameters, OXPHOS metabolism, ER-mitochondria distance, lysosomal activity, and may change the activation state of HSC. This study highlights that Cav-1 may modulate mitochondrial function and structural reorganization in HSC activation, being a potential candidate marker for chronic liver diseases and a molecular target for therapeutic intervention.

p53 mutants G245S and R337H associated with the Li-Fraumeni syndrome regulate distinct metabolic pathways.

Li-Fraumeni and Li-Fraumeni-like syndromes (LFS/LFL) are hereditary cancer predisposition disorders associated with germline mutations in the TP53 tumor suppressor gene. Here, we stably expressed LFS/LFL-associated p53 mutants R337H and G245S in p53-null H1299 cells to study their cellular and molecular effects. Mutant proteins showed distinct oligomerization states and opposing effects on cell proliferation and viability. Stable expression of p53G245S enhanced cell proliferation and spheroid formation, while cells stably expressing p53R337H showed reduced proliferation and clonogenicity, along with increased cell death. Mass spectrometry analysis revealed that proteins whose expression was induced by p53R337H or p53G245S expression were related to distinct metabolic profiles. Proteins upregulated by p53G245S expression were associated with a Warburg phenotype, while proteins upregulated by p53R337H expression were related to oxidative phosphorylation and fatty acid oxidation. Differences in mitochondrial mass and activity between cells stably expressing p53R337H or p53G245S were further corroborated by High Resolution Respirometry, flow cytometry and qPCR assays. The implications of the different oncogenic properties of p53R337H and p53G245S on the clinical manifestation and treatment of LFS/LFL patients carrying these mutations are discussed.

NT5E gene and CD38 protein as potential prognostic biomarkers for childhood B-acute lymphoblastic leukemia.

The risk stratification of B-acute lymphoblastic leukemia (B-ALL) is based on clinical and biological factors. However, B-ALL has significant biological and clinical heterogeneity and 50% of B-ALL patients do not have defined prognostic markers. In this sense, the identification of new prognostic biomarkers is necessary. Considering different cohorts of childhood B-ALL patients, gene (DPP4/CD38/ENTPD1/NT5E) and protein (CD38/CD39/CD73) expressions of ectonucleotidases were analyzed in silico and ex vivo and the association with prognosis was established. In univariate analyses, expression of NT5E was significantly associated with worse progression-free survival (PFS) in bone marrow (BM) samples. In multivariate analyses, Kaplan-Meier analysis, and log-rank test, higher NT5E expression predicted unfavorable PFS in BM samples. Considering minimal residual disease (MRD), higher levels of cellularity were associated with the high NT5E expression at day 8 of induction therapy. In addition, we observed that white blood cells (WBC) of childhood B-ALL patients had more CD38 compared to the same cell population of healthy donors (HD). In fact, MRD > 0.1% patients had higher CD38 protein expression on WBC in comparison to HD. Noteworthy, we observed higher CD38 expression on WBC than blasts in MRD > 0.1% patients. We suggest that NT5E gene and CD38 protein expression, of the ectonucleotidases family, could provide interesting prognostic biomarkers for childhood B-ALL.

Sintomatologia depressiva e suas repercussões na representação social da depressão: um estudo com adolescentes

A depressão tem sido retratada como o mal do século, tornando-se um problema de saúde pública que tem afetado milhões de pessoas no mundo. Este estudo objetivou compreender como os adolescentes representam a depressão. Participaram 168 estudantes do ensino médio, com idades de 14 a 18 anos, de escolas públicas e privadas de João Pessoa-Paraíba, Brasil. Utilizou-se a Técnica de Associação Livre de Palavras (TALP), Questionário sociodemográfico e a Escala de Ansiedade e Depressão Hospitalar (HADS). Observou-se a representação social da depressão ancorada em vivências subjetivas enfatizando os aspectos individuais desse fenômeno como tristeza, solidão, angústia, sofrimento e suicídio. Os adolescentes apresentaram sintomatologia depressiva em 21,4 %, sendo estes percentuais acentuados quando comparados com outros estudos na área. Espera-se que este estudo possa promover ações de prevenção no contexto escolar e reflexões sobre meios de conscientização da depressão como um transtorno de causas múltiplas.

La depresión ha sido retratada como el mal del siglo, convirtiéndose en un problema de salud pública que ha afectado a millones de personas en todo el mundo. Este estudio tuvo como objetivo comprender cómo los adolescentes representan la depresión. Participaron 168 estudiantes de secundaria, de 14 a 18 años, de escuelas públicas y privadas en João Pessoa-Paraíba, Brasil. Se utilizó la técnica de asociación de palabras libres (TALP), Cuestionario sociodemográfico y la Escala de ansiedad y depresión hospitalaria (HADS). Se observó la representación social de la depresión anclada en experiencias subjetivas que enfatizan los aspectos individuales de este fenómeno como la tristeza, la soledad, la angustia, el sufrimiento y el suicidio. Los adolescentes presentaron síntomas depresivos en 21.4 %, estos porcentajes se acentuaron en comparación con otros estudios en el área. Se espera que este estudio pueda promover acciones preventivas en el contexto escolar y reflexiones sobre formas de crear conciencia sobre la depresión como un trastorno de múltiples causas.

Depression has been portrayed as the evil of the century, becoming a public health problem that has affected millions of people worldwide. This study aimed to understand how adolescents represent depression. One hundred and sixty-eight high school students aged 14 to 18 years participated, from public and private schools in João Pessoa-Paraíba, Brazil. We used the Free Association of Words Technique (TALP), a sociodemographic questionnaire, and the Hospital Anxiety and Depression Scale (HADS). The social representation of depression anchored in subjective experiences was observed, emphasizing the individual aspects of this phenomenon, such as sadness, loneliness, anguish, suffering and suicide. The adolescents presented depressive symptoms in 21.4 % of the cases, and these percentages are higher when compared to other studies in the area. It is hoped that this study can promote preventive actions in the school context and reflect on ways to raise awareness of depression as a disorder with multiple causes.