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1.
Mol Cell Endocrinol ; 592: 112348, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39218056

RESUMO

The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging. This led to the identification of commonly or inversely differentially expressed targets in early life and aging, revealing dysregulated pathways related to the immune system, stress, muscle contraction, tight junctions, and hemostasis. We identified three miRNAs (miR-378a-3p, miR-378a-5p, let-7a-5p) that regulate four proteins (ACTN4, PPIA, HSPA5, CALM1) as probable epigenetic lung marks generated by MPR. In conclusion, MPR impacts the lungs early in life, increasing the possibility of long-lasting negative outcomes for respiratory disorders in the offspring.


Assuntos
Pulmão , MicroRNAs , Proteômica , Animais , Feminino , Pulmão/metabolismo , Masculino , Proteômica/métodos , Gravidez , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/genética , Dieta com Restrição de Proteínas , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Longevidade/genética , Ratos Wistar , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteoma/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Envelhecimento/metabolismo , Envelhecimento/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-39239855

RESUMO

Fibroblasts, crucial for maintaining tissue homeostasis, significantly shape the tumor microenvironment (TME). In pancreatic cancer, a highly aggressive malignancy, cancer-associated fibroblast (CAF)/extracellular matrix (ECM) units dominate the TME, influencing tumor initiation, progression, and treatment responses. Palladin, an actin-associated protein, is vital for fibroblast structural integrity and activation, playing a key role in CAF/ECM functionality. Palladin interacts with cytoskeletal proteins such as alpha-actinin (α-Act) and can therefore regulate other proteins like syndecans, modulating cytoskeletal features, cell adhesion, integrin recycling, and signaling. In this review, we propose that targeting the palladin/α-Act/syndecan interaction network could modulate CAF/ECM units, potentially shifting the TME from a tumor-promoting to a tumor-suppressive state. In silico data and reported studies to suggest that stabilizing palladin-α-Act interactions, via excess palladin, influences syndecan functions; potentially modulating integrin endocytosis via syndecan engagement with protein kinase C alpha as opposed to syndecan binding to α-Act. This mechanism can then affect the distribution of active α5ß1-integrin between the plasma membrane and known intracellular vesicular compartments, thereby influencing the tumor-suppressive versus tumor-promoting functions of CAF/ECM units. Understanding these interactions offers likely future therapeutic avenues for stroma normalization in pancreatic and other cancers, aiming to inhibit tumor progression and improve future treatment outcomes.

3.
Rev Bras Enferm ; 77(4): e20230510, 2024.
Artigo em Inglês, Português | MEDLINE | ID: mdl-39258611

RESUMO

OBJECTIVE: to analyze the association between burnout and sociodemographic, work factors, lifestyle habits and health conditions of military police officers in a municipality in the state of Paraná, Brazil. METHOD: cross-sectional research with 131 military police officers. Data were analyzed using the Statistical Package for the Social Sciences software and the R program. Chi-square, Fisher's exact and Poisson Generalized Linear Model tests were used. RESULTS: most participants (65.6%) had a high level of burnout. In relation to protective factors, those who carried out leisure activities had a 33.6% chance of not developing burnout. Conjugality was also a protective factor. Not practicing physical activity and leisure activities are factors that can contribute to the occurrence of burnout. CONCLUSIONS: important factors and high rates of burnout were observed in the police officers investigated. It is necessary to implement public health policies to reduce burnout with attention focused on this professional category.


Assuntos
Esgotamento Profissional , Polícia , Humanos , Brasil/epidemiologia , Masculino , Polícia/psicologia , Polícia/estatística & dados numéricos , Estudos Transversais , Adulto , Feminino , Esgotamento Profissional/psicologia , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/etiologia , Pessoa de Meia-Idade , Militares/psicologia , Militares/estatística & dados numéricos , Inquéritos e Questionários
4.
Int J Mol Cell Med ; 13(1): 19-28, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39156872

RESUMO

Gallic acid (GA) is a powerful antioxidant extracted from plants of the Brazilian Cerrado. Oxidative stress plays an important role in the occurrence of radiation-induced osteonecrosis in patients treated for head and neck cancer. There is a need to develop research aimed at developing complementary therapies to prevent or reverse bone damage. The aim of the present study was to investigate the effect of GA in preosteoblasts exposed to therapeutic ionizing radiation. MC3T3-E1 preosteoblast cells were treated with 10 µM GA and exposed to 6 Gy ionizing radiation. We performed in vitro assays of cell proliferation, oxidative stress analysis by detection of reactive oxygen species, and alkaline phosphatase assay. GA at lower concentrations was able to significantly increase proliferation and inhibit radiation-induced generation of reactive oxygen species in osteoblast precursor cells, despite ionizing radiation-induced injury. Furthermore, GA significantly increased alkaline phosphatase at a dose of 6 Gy. The findings suggested that GA could attenuate ionizing radiation-induced injuries in osteoblast precursor cells. Moreover, in vivo studies are needed to better investigate the role of GA in osteonecrosis, especially in cancer patients undergoing radiotherapy or taking antiresorptive drugs.

5.
J Oral Pathol Med ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160673

RESUMO

OBJECTIVE: Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells. METHODS: Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies. RESULTS: Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53. CONCLUSIONS: This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions.

6.
J Nutr Biochem ; 134: 109721, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39128608

RESUMO

Malnutrition is a complicated illness that affects people worldwide and is linked to higher death rates, a heightened vulnerability to infections, and delayed cognitive development. Experimental models have been constructed to comprehend the mechanisms associated with hunger. In this regard, the current study used two different types of food aiming to validate a murine model of malnutrition based on dietary restriction. The study was conducted with fifty-six Swiss male mice (eight-week-old) divided into eight groups (n=7 each) and fed the following experimental diets (10 weeks): Standard Diet (ST) ad libitum; ST 20% dietary restriction; ST 40% dietary restriction; ST 60% dietary restriction; AIN93-M diet ad libitum; AIN93-M 20% dietary restriction; AIN93-M 40% dietary restriction; AIN93-M 60% dietary restriction. Body, biochemical, and histological parameters were measured, and the restriction effects on genes related to oxidative stress (GPX1 and GPX4) in epididymal adipose tissue were evaluated. The results obtained showed that 20%, 40%, and 60% of dietary restrictions were able to reduce body weight when compared to controls, highlighting the accentuated weight loss in animals with 60% restrictions, especially those fed with AIN-93 M, which showed physical changes such as whitish skin and dull coat, voracious eating, and hunched posture. The present animal model also showed biochemical changes with hypoalbuminemia, as well as histological epididymal adipose tissue modulation. The presence of increased oxidative stress was observed when evaluating the GPX4 gene. Given the results, 60% food restriction using the AIN93-M diet was the best protocol for inducing malnutrition.

7.
Adv Rheumatol ; 64(1): 58, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135131

RESUMO

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA. OBJECTIVE: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA. METHODS: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose. RESULTS: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines. CONCLUSION: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity.


Assuntos
Artrite Reumatoide , Vacinas contra COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Feminino , Masculino , Brasil/epidemiologia , Pessoa de Meia-Idade , COVID-19/prevenção & controle , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , ChAdOx1 nCoV-19/efeitos adversos , Estudos Prospectivos , Adulto , SARS-CoV-2/imunologia , Idoso , Cefaleia/induzido quimicamente , Cefaleia/etiologia , Mialgia/induzido quimicamente , Mialgia/etiologia , Artralgia/etiologia , Vacinas de Produtos Inativados
8.
J Med Food ; 27(8): 749-757, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39017636

RESUMO

The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT.


Assuntos
Farinha , Interleucina-6 , Músculo Esquelético , Miocinas , Treinamento Resistido , Animais , Humanos , Masculino , Camundongos , Composição Corporal/efeitos dos fármacos , Metabolismo Energético , Fibronectinas/metabolismo , Fibronectinas/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Músculo Esquelético/metabolismo , Miocinas/genética , Miocinas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Condicionamento Físico Animal , Termogênese/efeitos dos fármacos
9.
J Fish Biol ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38986516

RESUMO

The Rio de Janeiro Marine Aquarium (AquaRio) is the first to successfully maintain and reproduce the spiny butterfly ray (Gymnura altavela), providing unique information about the species' biology. Seven rays were kept in captivity between 2018 and 2023, two captured on the southeastern coast of Brazil and five born in the aquarium. The applied abiotic conditions and nutrition allowed for the survival, growth, and reproduction of these individuals. Growth parameters (asymptotic disk width-DW∞ and growth coefficient-k) were estimated based on the von Bertalanffy model using the Fabens method for males and females separately. The best models estimated DW∞ = 106.47 cm and k = 0.396 for males and DW∞ = 172.2 cm and k = 0.190 for females. Sexual dimorphism was corroborated, with females reaching larger sizes and presenting slower growth rates than males. The estimated k values were higher than those estimated for rays of similar size to G. altavela in the natural environment, probably due to the constant water temperature (around 25.5°C), food abundance, low population density, reduced predation rates, and high water quality in the captive environment. A comparison of the captivity findings with other studies on G. altavela age and growth in the Atlantic and Mediterranean indicates a broad phenotypic plasticity regarding growth. Three G. altavela reproductions were recorded, with size at birth appearing to be a key factor for pup's survival. Behavioral pattern observations associated with reproduction are also described, encompassing chasing and copulation, whereas the species' internal morphology is described through coelomic cavity ultrasound scanning.

10.
Exp Cell Res ; 440(2): 114136, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38909881

RESUMO

Considering the importance of alternative methodologies to animal experimentation, we propose an organoid-based biological model for in vitro blood vessel generation, achieved through co-culturing endothelial and vascular smooth muscle cells (VSMCs). Initially, the organoids underwent comprehensive characterization, revealing VSMCs (α-SMA + cells) at the periphery and endothelial cells (CD31+ cells) at the core. Additionally, ephrin B2 and ephrin B4, genes implicated in arterial and venous formation respectively, were used to validate the obtained organoid. Moreover, the data indicates exclusive HIF-1α expression in VSMCs, identified through various methodologies. Subsequently, we tested the hypothesis that the generated blood vessels have the capacity to modulate the osteogenic phenotype, demonstrating the ability of HIF-1α to promote osteogenic signals, primarily by influencing Runx2 expression. Overall, this study underscores that the methodology employed to create blood vessel organoids establishes an experimental framework capable of producing a 3D culture model of both venous and arterial endothelial tissues. This model effectively guides morphogenesis from mesenchymal stem cells through paracrine signaling, ultimately leading to an osteogenic acquisition phenotype, with the dynamic involvement of HIF-1α.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Músculo Liso Vascular , Miócitos de Músculo Liso , Organoides , Osteogênese , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Osteogênese/genética , Organoides/metabolismo , Organoides/citologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/citologia , Células Cultivadas , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/citologia , Vasos Sanguíneos/crescimento & desenvolvimento , Técnicas de Cocultura/métodos , Diferenciação Celular , Células Endoteliais/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia
11.
Mol Cell Endocrinol ; 592: 112316, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38880278

RESUMO

This study investigated the impact of maternal protein restriction (MPR) and early postnatal sugar consumption (SUG) on the liver health of adult male descendant rats. Male offspring of mothers fed a normal protein diet (NPD) or a low protein diet (LPD) were divided into four groups: Control (CTR), Sugar Control (CTR + SUG), LPD during gestation and lactation (GLLP), and LPD with sugar (GLLP + SUG). Sugar consumption (10% glucose diluted in water) began after weaning on day 21 (PND 21), and at 90 days (PND 90), rats were sacrificed for analysis. Sugar intake reduced food intake and increased water consumption in CTR + SUG and GLLP + SUG compared to CTR and GLLP. GLLP and GLLP + SUG groups showed lower body weight and total and retroperitoneal fat compared to CTR and CTR + SUG. CTR + SUG and GLLP + SUG groups exhibited hepatocyte vacuolization associated with increased hepatic glycogen content compared to CTR and GLLP. Hepatic catalase activity increased in GLLP compared to CTR. Proteomic analysis identified 223 differentially expressed proteins (DEPs) among experimental groups. While in the GLLP group, the DEPs enriched molecular pathways related to cellular stress, glycogen metabolic pathways were enriched in the GLLP + SUG and CTR + SUG groups. The association of sugar consumption amplifies the effects of MPR, deregulating molecular mechanisms related to metabolism and the antioxidant system.


Assuntos
Dieta com Restrição de Proteínas , Fígado , Proteômica , Animais , Fígado/metabolismo , Fígado/efeitos dos fármacos , Masculino , Feminino , Dieta com Restrição de Proteínas/efeitos adversos , Gravidez , Proteômica/métodos , Ratos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Redes e Vias Metabólicas/efeitos dos fármacos , Proteoma/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Ratos Wistar , Animais Recém-Nascidos , Lactação , Peso Corporal/efeitos dos fármacos
12.
Food Res Int ; 189: 114570, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876598

RESUMO

Edible insects are recognized as promising food sources due to their nutritional composition. Some species, such as Gryllus assimilis, contain proteins, lipids, and carbohydrates of high biological value, which regulate several metabolic functions, including the Renin-Angiotensin System (RAS). In this context, the present study aimed to assess the effects of dietary supplementation with whole Gryllus assimilis powder on the metabolism of malnourished mice. Thirty-two male Swiss mice were used and divided into four treatment groups. The groups were identified as (AIN93-M); AIN93-M + Gryllus assimilis diet (AIN93-M + GA); AIN93-M + Renutrition diet (AIN93-M + REN) and AIN93-M + Renutrition diet + Gryllus assimilis (AIN93-M + REN + GA). The results showed that whole Gryllus assimilis powder inclusion promotes recovery from protein-energy malnutrition, reduces adiposity, and improves glucose tolerance and insulin sensitivity. It also reduces total cholesterol, triglycerides, VLDL, and adipocyte area. We also observed a significant increase in the expression of RAS-related genes, such as ACE2 and MasR, followed by a reduction in Angiotensinogen and ACE. The main findings of the present study suggest the use of black cricket as a viable strategy for the prevention and treatment of protein-energy malnutrition, as well as the reduction of adiposity, and improvement of lipid and glycemic parameters, with antihypertensive potential.


Assuntos
Tecido Adiposo , Suplementos Nutricionais , Gryllidae , Desnutrição Proteico-Calórica , Sistema Renina-Angiotensina , Animais , Sistema Renina-Angiotensina/efeitos dos fármacos , Masculino , Camundongos , Desnutrição Proteico-Calórica/metabolismo , Desnutrição Proteico-Calórica/dietoterapia , Tecido Adiposo/metabolismo , Adiposidade , Resistência à Insulina
13.
Enferm. foco (Brasília) ; 15: 1-9, maio. 2024. ilus, tab
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1570425

RESUMO

Objetivo: Analisar o perfil dos profissionais da saúde de nível técnico e superior contaminados pela covid-19 no Brasil. Métodos: Estudo transversal, quantitativo, desenvolvido por meio dos dados da Pesquisa Nacional por Amostra de Domicílios (PNAD) COVID 2020, com 2.794 trabalhadores da saúde de nível técnico e superior. Foram consideradas as variáveis disponíveis no banco de dados da PNAD COVID, referentes aos meses de julho, agosto, setembro, outubro e novembro de 2020. Os dados da PNAD COVID foram transportados para um banco de dados criado no MS-Excel e analisados com estatísticas descritivas. Resultados: Os profissionais de nível técnico foram os que mais se contaminaram com a covid-19, principalmente nos estados de São Paulo, Rio de Janeiro e Maranhão; com as seguintes características: sexo feminino; da etnia parda; com domicílio já quitado, sendo este responsável pelo domicílio; não constituindo outro emprego; média de idade 40 anos; o principal sintoma evidenciado foi a dor de cabeça; e, mais de 80% não relataram apresentar comorbidades. Conclusão: O cenário atual pandêmico, para os profissionais da saúde, deixa em evidência os danos atuais e futuros, que podem afetar a saúde mental desses trabalhadores, tornando-se elucidado a necessidade de maiores estudos e olhares para esses trabalhadores. (AU)


Objective: To analyze the profile of technical and higher-level health professionals contaminated by covid-19 in Brazil. Methods: Cross-sectional, quantitative study, developed using data from the National Household Sample Survey (PNAD) COVID 2020, with 2,794 technical and higher-level health workers. The variables available in the PNAD COVID database for the months of July, August, September, October and November 2020 were considered. The PNAD COVID data were transported to a database created in MS-Excel and analyzed with statistics descriptive. Results: Professionals with a technical level were the ones who were most contaminated with covid-19, mainly in the states of São Paulo, Rio de Janeiro and Maranhão; with the following characteristics: female; of the mixed race; with the home already paid off, being responsible for the home; not constituting another job; mean age 40 years; the main symptom evidenced was headache; and more than 80% reported no comorbidities. Conclusion: The current pandemic scenario, for health professionals, highlights the current and future damage, which can affect the mental health of these workers, clarifying the need for further studies and perspectives on these workers. (AU)


Objetivo: Analizar el perfil de técnicos y profesionales de la salud de alto nivel contaminados por covid-19 en Brasil. Métodos: Estudio transversal, cuantitativo, desarrollado a partir de datos de la Encuesta Nacional por Muestra de Hogares (PNAD) COVID 2020, con 2.794 técnicos y trabajadores de la salud de nivel superior. Se consideraron las variables disponibles en la base de datos PNAD COVID para los meses de julio, agosto, septiembre, octubre y noviembre de 2020. Los datos de la PNAD COVID fueron transportados a una base de datos creada en MS-Excel y analizados con estadística descriptiva. Resultados: Los profesionales con nivel técnico fueron los más contaminados con covid-19, principalmente en los estados de São Paulo, Rio de Janeiro y Maranhão; con las siguientes características: femenino; del mestizo; con el hogar ya pagado, siendo responsable del hogar; no constituir otro trabajo; edad media 40 años; el síntoma principal evidenciado fue el dolor de cabeza; y más del 80% no informaron comorbilidades. Conclusión: El escenario pandémico actual, para los profesionales de la salud, resalta los daños actuales y futuros, que pueden afectar la salud mental de estos trabajadores, aclarando la necesidad de mayores estudios y perspectivas sobre estos trabajadores. (AU)


Assuntos
COVID-19 , Saúde Ocupacional , Pessoal de Saúde , Pandemias
15.
Gene ; 926: 148606, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38788813

RESUMO

Obesity and overweight are multifactorial diseases affecting more than one-third of the world's population. Physical inactivity contributes to a positive energy balance and the onset of obesity. Exercise combined with a balanced diet is an effective non-pharmacological strategy to improve obesity-related disorders. Gallic acid (GA), is a natural endogenous polyphenol found in a variety of fruits, vegetables, and wines, with beneficial effects on energetic homeostasis. The present study aims to investigate the effects of exercise training on obese mice supplemented with GA. Animal experimentation was performed with male Swiss mice divided into five groups: ST (standard control), HFD (obese control), HFD + GA (GA supplement), HFD + Trained (training), and HFD + GA + Trained (GA and training). The groups are treated for eight weeks with 200 mg/kg/body weight of the feed compound and, if applicable, physical training. The main findings of the present study show that GA supplementation improves liver fat, body weight, adiposity, and plasma insulin levels. In addition, animals treated with the GA and a physical training program demonstrate reduced levels of anxiety. Gene expression analyses show that Sesn2 is activated via PGC-1α independent of the GATOR2 protein, which is activated by GA in the context of physical activity. These data are corroborated by molecular docking analysis, demonstrating the interaction of GA with GATOR2. The present study contributes to understanding the metabolic effects of GA and physical training and demonstrates a new hepatic mechanism of action via Sestrin 2 and PGC-1α.


Assuntos
Ácido Gálico , Fígado , Camundongos Obesos , Obesidade , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Condicionamento Físico Animal , Animais , Camundongos , Ácido Gálico/farmacologia , Masculino , Fígado/metabolismo , Fígado/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/genética , Obesidade/tratamento farmacológico , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Ansiedade/tratamento farmacológico , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Sestrinas
16.
bioRxiv ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38798370

RESUMO

Understanding pancreatic cancer biology is fundamental for identifying new targets and for developing more effective therapies. In particular, the contribution of the stromal microenvironment to pancreatic cancer tumorigenesis requires further exploration. Here, we report the stromal roles of the synaptic protein Netrin G1 Ligand (NGL-1) in pancreatic cancer, uncovering its pro-tumor functions in cancer-associated fibroblasts and in immune cells. We observed that the stromal expression of NGL-1 inversely correlated with patients' overall survival. Moreover, germline knockout (KO) mice for NGL-1 presented decreased tumor burden, with a microenvironment that is less supportive of tumor growth. Of note, tumors from NGL-1 KO mice produced less immunosuppressive cytokines and displayed an increased percentage of CD8 + T cells than those from control mice, while preserving the physical structure of the tumor microenvironment. These effects were shown to be mediated by NGL-1 in both immune cells and in the local stroma, in a TGF-ß-dependent manner. While myeloid cells lacking NGL-1 decreased the production of immunosuppressive cytokines, NGL-1 KO T cells showed increased proliferation rates and overall polyfunctionality compared to control T cells. CAFs lacking NGL-1 were less immunosuppressive than controls, with overall decreased production of pro-tumor cytokines and compromised ability to inhibit CD8 + T cells activation. Mechanistically, these CAFs downregulated components of the TGF-ß pathway, AP-1 and NFAT transcription factor families, resulting in a less tumor-supportive phenotype. Finally, targeting NGL-1 genetically or using a functionally antagonistic small peptide phenocopied the effects of chemotherapy, while modulating the immunosuppressive tumor microenvironment (TME), rather than eliminating it. We propose NGL-1 as a new local stroma and immunomodulatory molecule, with pro-tumor roles in pancreatic cancer. Statement of Significance: Here we uncovered the pro-tumor roles of the synaptic protein NGL-1 in the tumor microenvironment of pancreatic cancer, defining a new target that simultaneously modulates tumor cell, fibroblast, and immune cell functions. This study reports a new pathway where NGL-1 controls TGF-ß, AP-1 transcription factor members and NFAT1, modulating the immunosuppressive microenvironment in pancreatic cancer. Our findings highlight NGL-1 as a new stromal immunomodulator in pancreatic cancer.

17.
Mol Cell Endocrinol ; 591: 112268, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38735622

RESUMO

Menopause causes important bodily and metabolic changes, which favor the increased occurrence of cardiovascular diseases, obesity, diabetes, and osteoporosis. Resveratrol exerts proven effects on body metabolism, improving glucose and lipid homeostasis and reducing inflammation and oxidative stress in various organs and tissues. Accordingly, this study evaluates the effects of resveratrol supplementation on the expression of markers associated with thermogenesis in brown adipose tissue, and on the body, metabolic and hormonal parameters of female mice submitted to bilateral oophorectomy. Eighteen female mice were randomized into three groups: G1: control (CONTROL), G2: oophorectomy (OOF), and G3: oophorectomy + resveratrol (OOF + RSV); the animals were kept under treatment for twelve weeks, being fed a standard diet and treated with resveratrol via gavage. Body, biochemical, hormonal, and histological parameters were measured; in addition to the expression of markers associated with thermogenesis in brown adipose tissue. The results showed that animals supplemented with resveratrol showed reduced body weight and visceral adiposity, in addition to glucose, total cholesterol, and triglyceride levels; decreased serum FSH levels and increased estrogen levels were observed compared to the OOF group and mRNA expression of PRDM16, UCP1, and SIRT3 in brown adipose tissue. The findings of this study suggest the important role of resveratrol in terms of improving body, metabolic, and hormonal parameters, as well as modulating markers associated with thermogenesis in brown adipose tissue of female mice submitted to oophorectomy.


Assuntos
Tecido Adiposo Marrom , Suplementos Nutricionais , Ovariectomia , Resveratrol , Termogênese , Proteína Desacopladora 1 , Animais , Resveratrol/farmacologia , Resveratrol/administração & dosagem , Feminino , Termogênese/efeitos dos fármacos , Termogênese/genética , Camundongos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Administração Oral , Regulação da Expressão Gênica/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Peso Corporal/efeitos dos fármacos , Hormônios/sangue
18.
Food Res Int ; 181: 114083, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448094

RESUMO

Malnutrition is considered one of the major public health problems worldwide and negatively affects the growth, development and learning of schoolchildren. This study developed and evaluated a fermented milk drink with added Umbu (Spondias tuberosa) pulp in the weight gain and renutrition of mice submitted to malnutrition by calorie restriction, and in malnourished children. The supplementation with this fermented milk drink contributed to an increase of 7.2 % in body weight, and 64.3 % in albumin, and a reduction of 35 % in cholesterol in malnourished mice. In humans, a group of nine malnourished children consumed a daily 200 mL serving of the milk drink (for 60 days). For humans, the fermented milk drink allowed an increase of 16.5 % in body weight, and 20.9 % in body mass index in malnourished children. In conclusion, fermented milk drink has a positive effect on the re-nutrition of malnourished mice and helps to improve the nutritional status of malnourished children.


Assuntos
Anacardiaceae , Desnutrição , Criança , Humanos , Animais , Camundongos , Soro do Leite , Leite , Estado Nutricional , Proteínas do Soro do Leite , Aumento de Peso , Peso Corporal
19.
J Dev Orig Health Dis ; 15: e4, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38500346

RESUMO

The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln. Epi significantly increased the Pgc-1α protein in the MO group of offspring at 110 pnd (p < 0.036, MO vs. MO+Epi), while at 245 pnd, Epi increased Fndc5/irisin mRNA expression in the MO+Epi group versus the MO group (p = 0.006).No differences were detected in Fndc5/irisin, Ucp3 or Sln mRNA or protein levels (including Pgc-1α mRNA) in the offspring at 110 pnd or in Pgc-1α, Ucp3, or Sln mRNA or protein levels (including Fndc5/irisin protein) at 245 pnd among the experimental groups. In conclusion, (-)-epicatechin treatment increased Fndc5/irisin mRNA expression and Pgc-α protein levels in the gastrocnemius muscle of offspring at postnatal days 110 and 245. Furthermore, it is suggested that the flavonoid effect in a model of obesity and its impact on thermogenesis in skeletal muscle are regulated by a different pathway than Fndc5/irisin.


Assuntos
Catequina , Obesidade Materna , Humanos , Gravidez , Ratos , Masculino , Feminino , Animais , Catequina/farmacologia , Fibronectinas/genética , Fibronectinas/metabolismo , Fibronectinas/farmacologia , Músculo Esquelético/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade Materna/metabolismo , RNA Mensageiro/genética
20.
Mol Cell Endocrinol ; 588: 112223, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556160

RESUMO

Maternal malnutrition can alter developmental biology, programming health and disease in offspring. The increase in sugar consumption during the peripubertal period, a worldwide concern, also affects health through adulthood. Studies have shown that maternal exposure to a low protein diet (LPD) is associated with an increase in prostate disease with aging. However, the combined effects of maternal LPD and early postnatal sugar consumption on offspring prostate disorders were not investigated. The effects on aging were evaluated using a maternal gestational model with lactational LPD (6% protein) and sugar consumption (10%) from postnatal day (PND) 21-90, associating the consequences on ventral prostate (VP) rats morphophysiology on PND540. An increase was shown in mast cells and in the VP of the CTR + SUG and Gestational and Lactational Low Protein (GLLP) groups. In GLLP + SUG, a significant increase was shown in TGF-ß1 expression in both the systemic and intra-prostatic forms, and SMAD2/3p had increased. The study identified maternal LPD and sugar consumption as risk factors for prostatic homeostasis in senility, activating the TGFß1-SMAD2/3 pathway, a signaling pathway with potential markers for prostatic disorders.


Assuntos
Desnutrição , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal , Próstata , Doenças Prostáticas , Animais , Masculino , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Doenças Prostáticas/patologia , Doenças Prostáticas/etiologia , Doenças Prostáticas/metabolismo , Desnutrição/complicações , Próstata/metabolismo , Próstata/patologia , Ratos , Inflamação/patologia , Inflamação/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Dieta com Restrição de Proteínas/efeitos adversos , Proteína Smad2/metabolismo , Ratos Wistar , Proteína Smad3/metabolismo , Proteína Smad3/genética , Transdução de Sinais , Animais Recém-Nascidos , Mastócitos/metabolismo
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