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1.
Nutrients ; 16(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38613028

RESUMO

(1) Background: Dietary behaviour transformation is imperative for the attainment of more sustainable food systems, including an increased intake of plant-based foods and lower consumption of red meat and highly processed foods. The influence of news media coverage on public opinion regarding dietary behaviours is significant. Therefore, this study aimed to explore how sustainable/plant-based diets have been portrayed in Australian news media. (2) Methods: The Factiva global news database was used to search news articles published in Australia between 2018 and 2020. Relevant news articles were selected if they included keywords relating to sustainable diets, plant-based diets, and meat alternatives. We used a coding protocol to extract key information, such as date of publication, article topic, and any health, environmental and economic impacts. Then, we performed a framing and thematic analysis of the data. (3) Results: From 357 included articles, more than half of the articles encouraged increasing the intake of plant-based foods (53.5%) and reducing animal-derived food intake (55.2%). Several reasons for such shift from animal protein centric Australian diets were identified throughout the articles such as health benefits (15.4%), environmental impacts (11.2%), animal welfare (4.8%), seasonality and local food intake (5.3%), avoiding overconsumption (4.5%) and food wastage (4.5%). (4) Conclusions: The predominant frame in Australian news coverage about sustainable diets has been about consumption, more plant- and less animal-based products, with little nuance about the complex interplay of diet quality and environment in influencing food choices. Australian news media should broaden its coverage of sustainable diets to include health, environmental, and economic factors to improve public understanding and facilitate informed and sustainable food choices. Further research is needed to enhance comprehension of how the audience perceives media coverage on this topic, which will provide a more thorough understanding.


Assuntos
60426 , Dieta , Animais , Austrália , Meios de Comunicação de Massa , Alimentos
2.
Cell Biol Int ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591778

RESUMO

Anoikis is a process of programmed cell death induced by the loss of cell/matrix interactions. In previous work, we have shown that the acquisition of anoikis resistance upregulates syndecan-4 (SDC4) expression in endothelial cells. In addition, SDC4 gene silencing by microRNA interference reverses the transformed phenotype of anoikis-resistant endothelial cells. Due to this role of SDC4 in regulating the behavior of anoikis-resistant endothelial cells, we have evaluated that the functional consequences of SDC4 silencing in the extracellular matrix (ECM) remodeling in anoikis-resistant rabbit aortic endothelial cells submitted to SDC4 gene silencing (miR-Syn4-Adh-1-EC). For this, we evaluated the expression of adhesive proteins, ECM receptors, nonreceptor protein-tyrosine kinases, and ECM-degrading enzymes and their inhibitors. Altered cell behavior was monitored by adhesion, migration, and tube formation assays. We found that SDC4 silencing led to a decrease in migration and angiogenic capacity of anoikis-resistant endothelial cells; this was accompanied by an increase in adhesion to fibronectin. Furthermore, after SDC4 silencing, we observed an increase in the expression of fibronectin, collagen IV, and vitronectin, and a decrease in the expression of integrin α5ß1 and αvß3, besides that, silenced cells show an increase in Src and FAK expression. Quantitative polymerase chain reaction and Western blot analysis demonstrated that SDC4 silencing leads to altered gene and protein expression of MMP2, MMP9, and HSPE. Compared with parental cells, SDC4 silenced cells showed a decrease in nitric oxide production and eNOS expression. In conclusion, these data demonstrate that SDC4 plays an important role in ECM remodeling. In addition, our findings represent an important step toward understanding the mechanism by which SDC4 can reverse the transformed phenotype of anoikis-resistant endothelial cells.

3.
Artif Intell Med ; 149: 102814, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462277

RESUMO

Machine Learning models need large amounts of annotated data for training. In the field of medical imaging, labeled data is especially difficult to obtain because the annotations have to be performed by qualified physicians. Natural Language Processing (NLP) tools can be applied to radiology reports to extract labels for medical images automatically. Compared to manual labeling, this approach requires smaller annotation efforts and can therefore facilitate the creation of labeled medical image data sets. In this article, we summarize the literature on this topic spanning from 2013 to 2023, starting with a meta-analysis of the included articles, followed by a qualitative and quantitative systematization of the results. Overall, we found four types of studies on the extraction of labels from radiology reports: those describing systems based on symbolic NLP, statistical NLP, neural NLP, and those describing systems combining or comparing two or more of the latter. Despite the large variety of existing approaches, there is still room for further improvement. This work can contribute to the development of new techniques or the improvement of existing ones.


Assuntos
Processamento de Linguagem Natural , Radiologia , Aprendizado de Máquina
4.
Artigo em Inglês | MEDLINE | ID: mdl-38541297

RESUMO

(1) Background: Food choices and systems have contributed to various health and environmental issues, resulting in the global syndemic (obesity, undernutrition and climate change). Studies show that revitalizing Indigenous food systems and including native plant-based foods in our diet may be important for promoting health, reducing diet-linked chronic diseases and mitigating environmental changes. However, it is still a challenge to 'Indigenize' research by including Aboriginal people in all project phases to achieve culturally appropriate collaboration. We describe the development of a protocol using co-design methods to explore how knowledge can be exchanged around Aboriginal food practices related to native plant-based foods to facilitate benefits and share opportunities for sustainable food systems and Aboriginal aspirations, as well as to promote health in these communities. (2) Methods: This qualitative study includes five phases. In Phase I, we will start building a trusting relationship with the communities and train the research team. In Phase II, we will receive the consent to co-design and establish the Aboriginal Reference Group to ensure that Aboriginal people will lead this project. In Phase III, the investigators will run the interviews/focus groups and record the discussions about the community's place-based needs, understanding the community aspirations for a sustainable food system and the potential opportunities for doing research and strengthening community between research and community. In Phase IV, the records will be analyzed with the Aboriginal Reference Group, and summaries will be shared with community members. Phase V will establish case studies to support the implementation of community aspirations. (3) Discussion: This study protocol describes the process of ensuring that research for sustainable food systems meets Indigenous aspirations and health promotion in Indigenous communities.


Assuntos
Dieta , Promoção da Saúde , Serviços de Saúde do Indígena , Humanos , Promoção da Saúde/métodos , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres
5.
Nutr Metab Cardiovasc Dis ; 34(4): 1088-1096, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38403484

RESUMO

BACKGROUND AND AIMS: Bisphenol A (BPA), an endocrine disruptor widely used in food contact materials, has been linked to a worse health profile. This study intends to estimate the association between BPA exposure and cardiometabolic patterns at adolescence. METHODS AND RESULTS: Data from the Portuguese population-based birth cohort Generation XXI at the age of 13 were used (n = 2386 providing 3-day food diaries and fasting blood samples). BPA exposure was measured in 24-h urine from a subsample (n = 206) and then predicted in all participants using a random forest method and considering dietary intake from diaries. Three cardiometabolic patterns were identified (normal, modified lipid profile and higher cardiometabolic risk) using a probabilistic Gaussian mixture model. Multinomial regression models were applied to associate BPA exposure (lower, medium, higher) and cardiometabolic patterns, adjusting for confounders. The median BPA exposure was 1532 ng/d, corresponding to 29.4 ng/kg/d. Adolescents higher exposed to BPA (compared to medium and lower levels) had higher BMI z-score (kg/m2) (0.68 vs. 0.39 and 0.52, respectively; p = 0.008), higher levels of body fat (kg) (16.3 vs. 13.8 and 14.6, respectively; p = 0.002), waist circumference (76.2 vs. 73.7 and 74.9, respectively; p = 0.026), insulinemia (ug/mL) (14.1 vs. 12.7 and 13.1, respectively; p = 0.039) and triglyceridemia (mg/dL) (72.7 vs. 66.1 and 66.5, respectively; p = 0.030). After adjustment, a significant association between higher BPA and a higher cardiometabolic risk pattern was observed (OR: 2.55; 95%CI: 1.41, 4.63). CONCLUSION: Higher BPA exposure was associated with a higher cardiometabolic risk pattern in adolescents, evidencing the role of food contaminants in health.


Assuntos
Doenças Cardiovasculares , Disruptores Endócrinos , Humanos , Adolescente , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/urina , Fenóis/efeitos adversos , Fenóis/urina , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/urina , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia
6.
Biochim Biophys Acta Rev Cancer ; 1878(6): 189011, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37923232

RESUMO

Cancer remains a leading cause of mortality. Despite significant breakthroughs in conventional therapies, treatment is still far from ideal due to high toxicity in normal tissues and therapeutic inefficiency caused by short drug lifetime in the body and resistance mechanisms. Current research moves towards the development of multifunctional nanosystems for delivery of chemotherapeutic drugs, bioactives and/or radionuclides that can be combined with other therapeutic modalities, like gene therapy, or imaging to use in therapeutic screening and diagnosis. The preparation and characterization of Lyotropic Liquid Crystalline (LLC) mesophases self-assembled as 2D and 3D structures are addressed, with an emphasis on the unique properties of these nanoassemblies. A comprehensive review of LLC nanoassemblies is also presented, highlighting the most recent advances and their outstanding advantages as drug delivery systems, including tailoring strategies that can be used to overcome cancer challenges. Therapeutic agents loaded in LLC nanoassemblies offer qualitative and quantitative enhancements that are superior to conventional chemotherapy, particularly in terms of preferential accumulation at tumor sites and promoting enhanced cancer cell uptake, lowering tumor volume and weight, improving survival rates, and increasing the cytotoxicity of their loaded therapeutic agents. In terms of quantitative anticancer efficacy, loaded LLC nanoassemblies reduced the IC50 values from 1.4-fold against lung cancer cells to 125-fold against ovarian cancer cells.


Assuntos
Cristais Líquidos , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Cristais Líquidos/química
7.
Nutrients ; 15(20)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37892522

RESUMO

Mild-to-moderate iodine deficiency during pregnancy is prevalent worldwide, but its consequences for maternal and child health are not clear. We aimed to investigate the impact of maternal iodine intake during pregnancy on the child's growth and neurodevelopment. This study involved a cohort of 11-year-old children (n = 70) whose mothers had participated in an iodine intake survey during pregnancy. Gestational, neonatal, anthropometric, intelligence quotient (IQ), and socioeconomic parameters were analyzed according to maternal urinary iodine concentration (UIC). There was a positive linear trend of current height Z-score, full-scale IQ, verbal IQ, family income, maternal education, and a negative trend of neonatal TSH levels with increasing maternal UIC levels. However, regression analysis indicated that maternal UIC was not an independent predictor of any gestational, neonatal, or childhood development parameter. Only maternal school education was positively associated with child height and IQ. In conclusion, we did not find any evidence of a direct effect of maternal iodine intake during pregnancy on the long-term growth and neurodevelopment of children. The results suggest that socioeconomic factors are important confounding factors that affect both maternal iodine intake and child development and must be considered when investigating the association between maternal iodine intake and child outcomes.


Assuntos
Iodo , Gravidez , Feminino , Recém-Nascido , Humanos , Criança , Seguimentos , Desenvolvimento Infantil , Mães , Estado Nutricional
8.
Food Res Int ; 173(Pt 1): 113251, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803563

RESUMO

Bisphenol A (BPA) is an endocrine disruptor used in food contact materials, by the application of polycarbonate plastics and epoxy resins. The main objective of this study is to compare the estimate of daily BPA exposure at 13 years of age and in the adult Portuguese population, using different methodological approaches, and assess the associations between this exposure and sociodemographic characteristics. METHODOLOGY: Cross-sectional data of 13-years follow-up from a population-based birth cohort Generation XXI (GXXI) (n = 2804) and from the National Food, Nutrition and Physical Activity Survey (IAN-AF 2015-2016) (n = 3845, ≥18 years old) was used. Dietary information was collected through three food diaries for adolescents and two non-consecutive 24-hour-recalls for adults. To estimate the daily exposure to BPA, three methodological approaches were used. "Food groups attribution" merged the food consumption data with the concentration of BPA in food groups. "Regression tree model" and "random forest" combined food consumption information with urinary BPA, measured in a subsample of 24-hour urine (in adolescents n = 216, and in adults n = 82), both used to predict BPA exposure in the remaining sample. The fit-index of the methodologies was assessed through the root mean square error (RMSE), mean absolute error (MAE) and Spearman correlation coefficient (ρ). Associations between BPA exposure and sociodemographic variables were tested by linear regression models, adjusted for sex, age groups (in adults) and educational level. Tolerable Daily Intake (TDI) of 0.2 ng/kg body weight (bw), recently proposed by the European Food Safety Authority (EFSA), was used for the risk characterization of BPA exposure. RESULTS: The "random forest" was found as the best methodology to estimate the daily BPA exposure (adolescents: RMSE = 0.989, MAE = 0.727, ρ = 0.168; adults: RMSE = 0.193, MAE = 0.147, ρ = 0.250). The median dietary BPA exposure, calculated by "food groups attribution", was 79.1 and 46.1 ng/kg bw/day for adolescents and adults, respectively, while "random forest" estimated a BPA exposure of 26.7 and 38.0 ng/kg bw/day. 99.9% of the Portuguese population presented a daily exposure above TDI. Male adolescents, females and higher educated adults, were those more exposed to BPA. CONCLUSIONS: The estimated daily BPA exposure strongly depends on the methodological approach. Food groups attribution may overestimate the exposure while the random forest appears to be a better methodological approach to estimate BPA exposure. Nevertheless, for all methods, the Portuguese population presented an unsafe BPA exposure by largely exceeding the safe levels proposed by EFSA.


Assuntos
Compostos Benzidrílicos , Fenóis , Adulto , Feminino , Adolescente , Humanos , Estudos Transversais , Fenóis/urina , Dieta , Peso Corporal
9.
Acta Med Port ; 36(12): 819-825, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37819731

RESUMO

INTRODUCTION: The International Health Regulations (IHR) were developed to prepare countries to deal with public health emergencies. The spread of SARS-CoV-2 underlined the need for international coordination, although few attempts were made to evaluate the integrated implementation of the IHR's core capacities in response to the COVID-19 pandemic. The aim of this study was to evaluate whether IHR shortcomings stem from non-compliance or regulatory issues, using Portugal as a European case study due to its size, organization, and previous discrepancies between self-reporting and peer assessment of the IHR's core capacities. METHODS: Fifteen public health medical residents involved in contact tracing in mainland Portugal interpreted the effectiveness of the IHR's core capabilities by reviewing the publicly available evidence and reflecting on their own field experience, then grading each core capability according to the IHR Monitoring Framework. The assessment of IHR enforcement considered efforts made before and after the onset of the pandemic, covering the period up to July 2021. RESULTS: Four out of nine core IHR capacities (surveillance; response; risk communication; and human resource capacity) were classified as level 1, the lowest. Only two were graded level 3 (preparedness; and laboratory), the highest. The remaining three) (national legislation, policy & financing; coordination and national focal point communication; and points of entry) were classified as level 2. CONCLUSION: Portugal exemplifies the extent to which implementation of the IHR was not fully achieved, which has resulted in the underperformance of several core capacities. There is a need to improve preparedness and international cooperation in order to harmonize and strengthen the global response to public health emergencies, with better political, institutional, and financial support.


Assuntos
COVID-19 , Regulamento Sanitário Internacional , Humanos , Controle de Doenças Transmissíveis/métodos , Pandemias/prevenção & controle , COVID-19/epidemiologia , Portugal/epidemiologia , Emergências , SARS-CoV-2 , Saúde Global , Organização Mundial da Saúde , Surtos de Doenças
10.
Pharmaceutics ; 15(8)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37631292

RESUMO

Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω3) have attracted the attention of the dermocosmetic and pharmaceutical sectors. However, both bioactives have inherent properties that limit their efficient skin delivery. Therefore, nanostructured lipid carriers (NLCs) and enriched PFC® hydrogels (HGs) have been developed as a dual-approach vehicle for Q and/or ω3 skin topical administration to improve bioactives' stability and skin permeation. Two NLC formulations were prepared with the same lipid composition but differing in surfactant composition (NLC1-soy lecithin and poloxamer 407; NLC2-Tween® 80 and dioctyl sodium sulfosuccinate (DOSS)), which have an impact on physicochemical properties and pharmaceutical and therapeutic performance. Despite both NLCs presenting high Q loading capacity, NLC2's physicochemical properties make them more suitable for topical skin administration and ensure longer colloidal stability. Additionally, NLC2 demonstrated a more sustained Q release, indicating higher bioactive storage while improving permeability. The occlusive effect of NLCs-enriched HGs also has a positive impact on skin permeability. Q-loaded NLC2, with or without ω3, -enriched HGs demonstrated efficacy as antioxidant and photoprotective formulations as well as effective reduction in S. aureus growth, indicating that they constitute a promising approach for topical skin administration to prevent skin aging and other damaging cutaneous processes.

11.
Theranostics ; 13(11): 3707-3724, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37441602

RESUMO

Background: Extracellular vesicles (EVs) carry bioactive molecules associated with various biological processes, including miRNAs. In both Huntington's disease (HD) models and human samples, altered expression of miRNAs involved in synapse regulation was reported. Recently, the use of EV cargo to reverse phenotypic alterations in disease models with synaptopathy as the end result of the pathophysiological cascade has become an interesting possibility. Methods: Here, we assessed the contribution of EVs to GABAergic synaptic alterations using a human HD model and studied the miRNA content of isolated EVs. Results: After differentiating human induced pluripotent stem cells into electrophysiologically active striatal-like GABAergic neurons, we found that HD-derived neurons displayed reduced density of inhibitory synapse markers and GABA receptor-mediated ionotropic signaling. Treatment with EVs secreted by control (CTR) fibroblasts reversed the deficits in GABAergic synaptic transmission and increased the density of inhibitory synapses in HD-derived neuron cultures, while EVs from HD-derived fibroblasts had the opposite effects on CTR-derived neurons. Moreover, analysis of miRNAs from purified EVs identified a set of differentially expressed miRNAs between manifest HD, premanifest, and CTR lines with predicted synaptic targets. Conclusion: The EV-mediated reversal of the abnormal GABAergic phenotype in HD-derived neurons reinforces the potential role of EV-miRNAs on synapse regulation.


Assuntos
Vesículas Extracelulares , Doença de Huntington , Células-Tronco Pluripotentes Induzidas , MicroRNAs , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , MicroRNAs/metabolismo , Neurônios GABAérgicos/metabolismo , Vesículas Extracelulares/metabolismo
12.
Pharmaceutics ; 15(7)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37514156

RESUMO

Nanosystems provide an attractive approach to pharmacological therapy, with the possibility of enhancing the performance and overcoming the constraints of conventional therapies, thus adding substantial value to some of the already available formulations [...].

13.
Foods ; 12(9)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37174400

RESUMO

The type of material used in packaging, lighting, and storage time can impact food quality during storage. This study aimed to investigate the progress of photosensitized oxidation in refined soybean oil using steady-state and time-resolved fluorescence spectroscopy. The experiment was conducted through accelerated photo-oxidation with Light-Emitting Diode (LED) in samples stored for ten days at room temperature (26.0 ± 2.0 °C) in clear polyethylene terephthalate (PET) packaging of different colors and different transmission spectra in the UV and visible range. Emission spectra were obtained with excitation at 373, 405, and 500 nm, resulting in two main emission peaks: the first with maximum emission between 430 and 555 nm and the second at around 660 nm. Fluorescence decay curves were obtained with excitation at 340 and 405 nm. The results indicated that transparent PET bottles are not effective in protecting soybean oil from photosensitized oxidation under the studied conditions. Strong correlations were observed between fluorescence parameters and peroxide and conjugated diene values, indicators of lipid oxidation progress. Fluorescence spectroscopy has several advantages over traditional methods as it is a simple, fast, low-cost, and low-waste technique.

14.
J Nucl Cardiol ; 30(6): 2327-2337, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37165114

RESUMO

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.


Assuntos
Cardiomiopatia Chagásica , Doença de Chagas , Pentoxifilina , Cricetinae , Animais , Feminino , Cardiomiopatia Chagásica/diagnóstico por imagem , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Tomografia Computadorizada por Raios X , Inflamação , Perfusão
15.
Pharmaceutics ; 15(4)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37111802

RESUMO

Cancer is one of the leading causes of death, and latest predictions indicate that cancer- related deaths will increase over the next few decades. Despite significant advances in conventional therapies, treatments remain far from ideal due to limitations such as lack of selectivity, non-specific distribution, and multidrug resistance. Current research is focusing on the development of several strategies to improve the efficiency of chemotherapeutic agents and, as a result, overcome the challenges associated with conventional therapies. In this regard, combined therapy with natural compounds and other therapeutic agents, such as chemotherapeutics or nucleic acids, has recently emerged as a new strategy for tackling the drawbacks of conventional therapies. Taking this strategy into consideration, the co-delivery of the above-mentioned agents in lipid-based nanocarriers provides some advantages by improving the potential of the therapeutic agents carried. In this review, we present an analysis of the synergistic anticancer outcomes resulting from the combination of natural compounds and chemotherapeutics or nucleic acids. We also emphasize the importance of these co-delivery strategies when reducing multidrug resistance and adverse toxic effects. Furthermore, the review delves into the challenges and opportunities surrounding the application of these co-delivery strategies towards tangible clinical translation for cancer treatment.

16.
Pharmaceuticals (Basel) ; 16(3)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36986527

RESUMO

Trypanosoma cruzi, the etiological agent of Chagas disease, relies on finely coordinated epigenetic regulation during the transition between hosts. Herein we targeted the silent information regulator 2 (Sir2) enzyme, a NAD+-dependent class III histone deacetylase, to interfere with the parasites' cell cycle. A combination of molecular modelling with on-target experimental validation was used to discover new inhibitors from commercially available compound libraries. We selected six inhibitors from the virtual screening, which were validated on the recombinant Sir2 enzyme. The most potent inhibitor (CDMS-01, IC50 = 40 µM) was chosen as a potential lead compound.

17.
Pharmaceutics ; 15(3)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36986617

RESUMO

Chagas disease is a neglected tropical disease that affects more than 8 million people. Although there are therapies against this disease, the search for new drugs is important because the current treatments show limited effectiveness and high toxicity. In this work, eighteen dihydrobenzofuran-type neolignans (DBNs) and two benzofuran-type neolignans (BNs) were synthesized and evaluated against amastigote forms of two Trypanosoma cruzi strains. The in vitro cytotoxicity and hemolytic activity of the most active compounds were also evaluated and their relationships with T. cruzi tubulin DBNs were investigated by an in silico approach. Four DBNs demonstrated activity against the T. cruzi Tulahuen lac-Z strain (IC50 from 7.96 to 21.12 µM), and DBN 1 exhibited the highest activity against the amastigote forms of the T. cruzi Y strain (IC50 3.26 µM). Compounds 1-4 showed CC50 values higher than antitrypanosomal activities, except for DBN 3. All DBNs with antitrypanosomal activity demonstrated CH50 higher than 100 µM. The in silico results indicated that DBNs 1, 2, and 4 are capable of destabilizing the dynamics of the tubulin-microtubule from the vinca site. These compounds displayed promising in vitro activity against T. cruzi, especially compound 1, and can be considered molecular prototypes for the development of new antiparasitic drugs.

18.
Int J Food Sci Nutr ; 74(3): 350-361, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36971097

RESUMO

This study aimed to explore the factors associated with the consumption of meat vs. meatless meals and to assess the applicability of a multi-state model to describe transitions between lunch and dinner. Fifteen thousand four hundred and eight main meals (lunch and dinner) from a sample of adults (18-84 years, n = 3852) from the Portuguese Food, Nutrition and Physical Activity Survey (IAN-AF 2015-2016) were categorised as meat, fish, ovolactovegetarian or snack. Adjusted generalised-mixed-effects models were used to explore the associations and a time-homogeneous Markov-multi-state model was applied to study the transitions. Women, older and higher educated individuals presented higher odds of consuming meatless meals and lower hazard of transitioning to meat in the following main meal. Strategies for replacing meat with more sustainable foods should be specific towards different population groups. Studying transitions across main meals, using multi-state models, can support the development of feasible, realistic and group-specific strategies to replace meat and promote dietary variety.


Assuntos
Comportamento Alimentar , Almoço , Feminino , Animais , Refeições , Dieta , Carne
19.
J Hum Nutr Diet ; 36(4): 1339-1348, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36794574

RESUMO

BACKGROUND: Parental child-feeding practices have been associated with child body mass index (BMI) and specific food group consumption; however, their role in the development of dietary patterns is less understood. We aim to study the association between parental child-feeding practices at 4 years old and dietary patterns at 7 years that explain BMI z-scores at age 10. METHODS: Participants were children from the Generation XXI birth cohort (n = 3272). Three patterns of feeding practices at 4 years were previously identified: 'Perceived monitoring', 'Restriction' and 'Pressure to eat'. At 7 years, two dietary patterns were derived: 'Energy-dense foods', higher consumption of energy-dense foods and drinks and processed meats and lower consumption of vegetable soup (significantly associated with BMI z-scores at 10 years) and 'Fish-based', higher in fishery intake and lower in energy-dense food intake. Associations were estimated by linear regression models, adjusted for potential confounders (mother's age, education and pre-pregnancy BMI). RESULTS: Girls whose parents used more Restriction, Perceived monitoring and Pressure to eat at 4 years were less likely to follow the 'Energy-dense foods' dietary pattern at 7 years (ß̂ = -0.082; 95% confidence intervals [CI]: -0.134; -0.029; ß̂ = -0.093; 95% CI: -0.146; -0.039; ß̂ = -0.079; 95% CI: -0.135; -0.04, respectively). In both sexes, children whose parents used more Restriction and Perceived monitoring at 4 years were more likely to follow the 'Fish-based' dietary pattern at 7 years (girls: ß̂ = 0.143; 95% CI: 0.077; 0.210; ß̂ = 0.079; 95% CI: 0.011; 0.148; boys: ß̂ = 0.157; 95% CI: 0.090; 0.224; ß̂ = 0.104; 95% CI: 0.041; 0.168). CONCLUSIONS: Children whose parents used more Restriction and Perceived monitoring at preschool age were more likely to follow healthier dietary patterns at age 7.


Assuntos
Dieta , Comportamento Alimentar , Masculino , Feminino , Gravidez , Animais , Humanos , Pré-Escolar , Índice de Massa Corporal , Pais , Verduras , Inquéritos e Questionários
20.
Dis Model Mech ; 16(2)2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36808468

RESUMO

Alterations in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression. Among those, P-cadherin is highly enriched in basal-like breast carcinomas, playing a central role in cancer cell self-renewal, collective cell migration and invasion. To establish a clinically relevant platform for functional exploration of P-cadherin effectors in vivo, we generated a humanized P-cadherin Drosophila model. We report that actin nucleators, Mrtf and Srf, are main P-cadherin effectors in fly. We validated these findings in a human mammary epithelial cell line with conditional activation of the SRC oncogene. We show that, prior to promoting malignant phenotypes, SRC induces a transient increase in P-cadherin expression, which correlates with MRTF-A accumulation, its nuclear translocation and the upregulation of SRF target genes. Moreover, knocking down P-cadherin, or preventing F-actin polymerization, impairs SRF transcriptional activity. Furthermore, blocking MRTF-A nuclear translocation hampers proliferation, self-renewal and invasion. Thus, in addition to sustaining malignant phenotypes, P-cadherin can also play a major role in the early stages of breast carcinogenesis by promoting a transient boost of MRTF-A-SRF signaling through actin regulation.


Assuntos
Actinas , Transativadores , Humanos , Actinas/metabolismo , Transativadores/metabolismo , Transdução de Sinais , Caderinas , Células Epiteliais/metabolismo , Fator de Resposta Sérica/genética , Fator de Resposta Sérica/metabolismo
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