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1.
PLoS Genet ; 19(11): e1011026, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37948444

RESUMO

The meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are localized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads to checkpoint inactivation. Here, we reveal the mechanism by which Pch2 travels from the cell nucleus to the cytoplasm to maintain Pch2 cellular homeostasis. Leptomycin B treatment provokes the nuclear accumulation of Pch2, indicating that its nucleocytoplasmic transport is mediated by the Crm1 exportin recognizing proteins containing Nuclear Export Signals (NESs). Consistently, leptomycin B leads to checkpoint inactivation and impaired Hop1 axial localization. Pch2 nucleocytoplasmic traffic is independent of its association with Zip1 and Orc1. We also identify a functional NES in the non-catalytic N-terminal domain of Pch2 that is required for its nucleocytoplasmic trafficking and proper checkpoint activity. In sum, we unveil another layer of control of Pch2 function during meiosis involving nuclear export via the exportin pathway that is crucial to maintain the critical balance of Pch2 distribution among different cellular compartments.


Assuntos
Proteínas de Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Meiose/genética , Saccharomyces cerevisiae/genética , Transporte Ativo do Núcleo Celular/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a DNA/genética , Carioferinas/genética , Carioferinas/metabolismo , Homeostase
2.
J Hum Evol ; 185: 103441, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37857126

RESUMO

Hispanopithecus laietanus from the Late Miocene (9.8 Ma) of Can Llobateres 1 (CLL1; Vallès-Penedès Basin, NE Iberian Peninsula) represents one of the latest occurrences of fossil apes in Western mainland Europe, where they are last recorded at ∼9.5 Ma. The paleoenvironment of CLL1 is thus relevant for understanding the extinction of European hominoids. To refine paleoenvironmental inferences for CLL1, we apply ecometric models based on functional crown type (FCT) variables-a scoring scheme devised to capture macroscopic functional traits of occlusal shape and wear surfaces of herbivorous large mammal molars. Paleotemperature and paleoprecipitation estimates for CLL1 are provided based on published regional regression models linking average FCT of large herbivorous mammal communities to climatic conditions. A mapping to Whittaker's present-day biome classification is also attempted based on these estimates, as well as a case-based reasoning via canonical variate analysis of FCT variables from five relevant biomes. Estimates of mean annual temperature (25 °C) and mean annual precipitation (881 mm) classify CLL1 as a tropical seasonal forest/savanna, only in partial agreement with the canonical variate analysis results, which classify CLL1 as a tropical rainforest with a higher probability. The former biome agrees better with previous inferences derived from fossil plants and mammals, as well as preliminary isotopic data. The misclassification of CLL1 as a tropical forest is attributed to the mixture of forest-adapted taxa with others adapted to more open environments, given that faunal and plant composition indicates the presence of a dense wetland/riparian forest with more open woodlands nearby. The tested FCT ecometric approaches do not provide unambiguous biome classification for CLL1. Nevertheless, our results are consistent with those from other approaches, thus suggesting that FCT variables are potentially useful to investigate paleoenvironmental changes through time and space-including those that led to the extinction of European Miocene apes.


Assuntos
Hominidae , Dente , Animais , Fósseis , Europa (Continente) , Ecossistema , Plantas , Mamíferos
3.
Int J Mol Sci ; 23(11)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35682708

RESUMO

Fatty acids have an important place in both biological and nutritional contexts and, from a clinical point of view, they have known consequences for diseases' onset and development, including cancer. The use of fatty acid-based food and nutraceuticals to support cancer therapy is a multidisciplinary subject, involving molecular and clinical research. Knowledge regarding polyunsaturated fatty acids essentiality/oxidizability and the role of lipogenesis-desaturase pathways for cell growth, as well as oxidative reactivity in cancer cells, are discussed, since they can drive the choice of fatty acids using their multiple roles to support antitumoral drug activity. The central role of membrane fatty acid composition is highlighted for the application of membrane lipid therapy. As fatty acids are also known as biomarkers of cancer onset and progression, the personalization of the fatty acid-based therapy is also possible, taking into account other important factors such as formulation, bioavailability and the distribution of the supplementation. A holistic approach emerges combining nutra- and pharma-strategies in an appropriate manner, to develop further knowledge and applications in cancer therapy.


Assuntos
Ácidos Graxos , Neoplasias , Suplementos Nutricionais , Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Humanos , Lipídeos de Membrana , Neoplasias/tratamento farmacológico
4.
Int J Mol Sci ; 23(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35163842

RESUMO

This work intends to describe the physical properties of red blood cell (RBC) membranes in obese adults. The hypothesis driving this research is that obesity, in addition to increasing the amount of body fat, will also modify the lipid composition of membranes in cells other than adipocytes. Forty-nine control volunteers (16 male, 33 female, BMI 21.8 ± 5.6 and 21.5 ± 4.2 kg/m2, respectively) and 52 obese subjects (16 male and 36 female, BMI 38.2± 11.0 and 40.7 ± 8.7 kg/m2, respectively) were examined. The two physical techniques applied were atomic force microscopy (AFM) in the force spectroscopy mode, which allows the micromechanical measurement of penetration forces, and fluorescence anisotropy of trimethylammonium diphenylhexatriene (TMA-DPH), which provides information on lipid order at the membrane polar-nonpolar interface. These techniques, in combination with lipidomic studies, revealed a decreased rigidity in the interfacial region of the RBC membranes of obese as compared to control patients, related to parallel changes in lipid composition. Lipidomic data show an increase in the cholesterol/phospholipid mole ratio and a decrease in sphingomyelin contents in obese membranes. ω-3 fatty acids (e.g., docosahexaenoic acid) appear to be less prevalent in obese patient RBCs, and this is the case for both the global fatty acid distribution and for the individual major lipids in the membrane phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). Moreover, some ω-6 fatty acids (e.g., arachidonic acid) are increased in obese patient RBCs. The switch from ω-3 to ω-6 lipids in obese subjects could be a major factor explaining the higher interfacial fluidity in obese patient RBC membranes.


Assuntos
Difenilexatrieno/análogos & derivados , Membrana Eritrocítica/fisiologia , Lipidômica/métodos , Obesidade/diagnóstico por imagem , Adolescente , Adulto , Fenômenos Biomecânicos , Estudos de Casos e Controles , Difenilexatrieno/administração & dosagem , Membrana Eritrocítica/metabolismo , Feminino , Polarização de Fluorescência , Humanos , Masculino , Microscopia de Força Atômica , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/fisiopatologia , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/metabolismo , Adulto Jovem
5.
Appetite ; 144: 104466, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31542382

RESUMO

Trends in the prevalence of childhood overweight and obesity in Europe and especially in Spain have continuously increased in the last three decades. The aim of this work was to study the healthiness understanding (healthy and unhealthy food) in children with different ages and to evaluate liking towards a set of school meals: first courses, second courses and fruit/dessert. Two hundred and seventy-seven children between the ages of six and twelve from three primary schools in northern Spain, Bizkaia, took part in this study. All the groups showed a good knowledge of the healthiness of the dishes offered in the school canteen. However, some dishes were difficult to assess for the 6-7- and 8-9-year old groups. Pasta and croquettes with chips were the most preferred dishes. Vegetables and fish dishes were the least preferred. Results suggest that children become increasingly aware of their preferences and critical in their choices with growing age. It was found in this study that there was a strongly inverse relationship between children's perceptions of the healthiness of foods and their preferences for them. The structured sorting task was a good tool for children to classify various dishes (complex food) considering healthiness and hedonic perception at the same time. In conclusion, these results contribute to a better understanding of children's nutritional perception (healthy/unhealthy food) and its relation to preferences of school meals, which is important for quality improvement and nutritional planning in school food services.


Assuntos
Dieta Saudável/psicologia , Preferências Alimentares/psicologia , Serviços de Alimentação , Conhecimentos, Atitudes e Prática em Saúde , Refeições/psicologia , Criança , Comportamento de Escolha , Feminino , Humanos , Masculino , Filosofia , Serviços de Saúde Escolar , Instituições Acadêmicas , Espanha
6.
Sensors (Basel) ; 20(18)2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32899921

RESUMO

Obesity is a preventable chronic condition that, in 2016, affected more than 1.9 billion people globally. Several factors have been identified that have a positive impact on long-term weight loss programs such as personalized recommendations, adherence strategies, weight and diet follow-up or physical activity tracking. Recently, various applications have been developed which help patients to self-manage their condition. These apps implement either one or some of these identified factors; however, there is not a single application that combines all of them following a holistic approach. In this context, we developed the OBINTER platform, which assists patients during the weight loss process by targeting user engagement during the longer term. The solution includes a mobile application which allows users to fill out dietetic questionnaires, receive dietetic and nutraceutical plans, track the evolution of their weight and adherence to the diet, as well as track their physical activity via a wearable device. Furthermore, an adherence strategy has been developed as a tool to foster the app usage during the whole weight loss process. In this paper, we present how the OBINTER approach gathers all of these features as well as the positive results of a usability testing study performed to assess the performance and usability of the OBINTER platform.


Assuntos
Aplicativos Móveis , Obesidade/terapia , Autogestão , Catálise , Feminino , Humanos , Masculino , Redução de Peso
7.
Nucleic Acids Res ; 44(16): 7722-41, 2016 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-27257060

RESUMO

Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes.


Assuntos
Adenosina Trifosfatases/metabolismo , Pontos de Checagem do Ciclo Celular , Proteínas de Ligação a DNA/metabolismo , Meiose , Proteínas Nucleares/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Complexo Sinaptonêmico/metabolismo , Trifosfato de Adenosina/metabolismo , Sítios de Ligação , Pareamento Cromossômico , Quebras de DNA de Cadeia Dupla , Genes Supressores , Testes Genéticos , Viabilidade Microbiana , Modelos Biológicos , Mutação/genética , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Esporos Fúngicos/fisiologia
8.
Mediators Inflamm ; 2017: 3674390, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28484308

RESUMO

Objective. To evaluate the long-term effects of a Mediterranean diet (MeDiet) intervention on the plasma concentrations of inflammatory and plaque stability-related molecules in elderly people at high risk for cardiovascular disease. Design and Setting. 66 participants from primary care centers affiliated with the Hospital Clinic of Barcelona were randomized into 3 groups: MeDiet plus extra virgin olive oil (EVOO) or nuts and a low-fat diet (LFD). At baseline and at 3 and 5 years, we evaluated the changes in the plasma concentrations of 24 inflammatory biomarkers related to the different stages of the atherosclerotic process by Luminex®. Results. At 3 and 5 years, both MeDiet groups showed a significant reduction of IL-6, IL-8, MCP-1, and MIP-1ß (P < 0.05; all) compared to LFD. IL-1ß, IL-5, IL-7, IL-12p70, IL-18, TNF-α, IFN-γ, GCSF, GMCSF, and ENA78 (P < 0.05; all) only decreased in the MeDiet+EVOO group and E-selectin and sVCAM-1 (P < 0.05; both) in the MeDiet+nuts group. Conclusions. Long-term adherence to MeDiet decreases the plasma concentrations of inflammatory biomarkers related to different steps of atheroma plaque development in elderly persons at high cardiovascular risk.


Assuntos
Aterosclerose/dietoterapia , Aterosclerose/patologia , Dieta Mediterrânea , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/metabolismo , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Quimiocina CCL4/metabolismo , Quimiocina CCL5/metabolismo , Dieta com Restrição de Gorduras , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-18/metabolismo , Interleucina-6/metabolismo , Lipoproteínas LDL/metabolismo , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/dietoterapia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Fatores de Risco , Molécula 1 de Adesão de Célula Vascular/metabolismo
9.
Circ Res ; 111(8): 1065-8, 2012 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-22955728

RESUMO

RATIONALE: Experimental studies have shown a potential blood pressure (BP) lowering effect of red wine polyphenols, whereas the effects of ethanol and polyphenols on BP in humans are not yet clear. OBJECTIVE: The aim of the present work was to evaluate the effects of red wine fractions (alcoholic and nonalcoholic) on BP and plasma nitric oxide (NO) in subjects at high cardiovascular risk. METHODS AND RESULTS: Sixty-seven men at high cardiovascular risk were studied. After a 2-week run-in period, subjects were randomized into 3 treatment periods in a crossover clinical trial, with a common background diet plus red wine (30g alcohol/day), the equivalent amount of dealcoholized red wine, or gin (30g alcohol/day), lasting 4 weeks each intervention. At baseline and after each intervention, anthropometrical parameters, BP and plasma NO were measured. Systolic and diastolic BP decreased significantly after the dealcoholized red wine intervention and these changes correlated with increases in plasma NO. CONCLUSIONS: Dealcoholized red wine decreases systolic and diastolic BP. Our results point out through an NO-mediated mechanism. The daily consumption of dealcoholized red wine could be useful for the prevention of low to moderate hypertension. Trial registered at controlled-trials.com: ISRCTN88720134.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Óxido Nítrico/sangue , Polifenóis/administração & dosagem , Vinho , Idoso , Pressão Sanguínea/fisiologia , Depressores do Sistema Nervoso Central/administração & dosagem , Estudos Cross-Over , Etanol/administração & dosagem , Humanos , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento de Redução do Risco , Resultado do Tratamento
10.
Artigo em Inglês | MEDLINE | ID: mdl-38147804

RESUMO

The levels of blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are very variable and, in general, low in most of the world population. In this study, the effects of age, sex, COVID-19, and dietary habits on the lipid profile of the erythrocyte membranes were assessed in a sub-cohort of healthy population (N = 203) from a large cohort of individuals from the Basque Country, Spain, (AKRIBEA). Sex did not have an effect on RBC lipid profile. COVID-19 infected participants showed higher levels of DGLA. Oldest participants showed higher oleic acid, EPA and DHA levels. Arachidonic acid in RBC correlated positively with the intake of sunflower oil, butter, eggs, processed and red meat, whereas DHA and EPA correlated positively with oily and lean fish. Basque Country population showed lipid profiles similar to other high fish consuming countries, such as Italy and Japan. Baseline levels of the whole lipidomic profile of the RBC including SFA, MUFA and PUFA should be examined to obtain a better description of the health and nutritional status.


Assuntos
COVID-19 , Ácidos Graxos Ômega-3 , Animais , Humanos , Ácidos Graxos , Espanha , Membrana Eritrocítica/metabolismo , Ácido Eicosapentaenoico , Ácidos Docosa-Hexaenoicos , Europa (Continente) , Comportamento Alimentar , COVID-19/epidemiologia
11.
Alcohol Alcohol ; 48(3): 270-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23408240

RESUMO

AIMS: The aim of this review was to focus on the knowledge of the cardiovascular benefits of moderate alcohol consumption, as well as to analyze the effects of the different types of alcoholic beverages. METHODS: Systematic revision of human clinical studies and meta-analyses related to moderate alcohol consumption and cardiovascular disease (CVD) from 2000 to 2012. RESULTS: Heavy or binge alcohol consumption unquestionably leads to increased morbidity and mortality. Nevertheless, moderate alcohol consumption, especially alcoholic beverages rich in polyphenols, such as wine and beer, seems to confer cardiovascular protective effects in patients with documented CVD and even in healthy subjects. CONCLUSIONS: In conclusion, wine and beer (but especially red wine) seem to confer greater cardiovascular protection than spirits because of their polyphenolic content. However, caution should be taken when making recommendations related to alcohol consumption.


Assuntos
Doenças Cardiovasculares/epidemiologia , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Polifenóis/farmacologia , Vinho , Bebidas Alcoólicas/toxicidade , Aterosclerose/epidemiologia , Aterosclerose/prevenção & controle , Cerveja , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Depressores do Sistema Nervoso Central/efeitos adversos , Depressores do Sistema Nervoso Central/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Etanol/efeitos adversos , Etanol/uso terapêutico , Humanos , Lipídeos/sangue , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/uso terapêutico , Fatores de Risco , Caracteres Sexuais
12.
Biomedicines ; 11(12)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38137540

RESUMO

BACKGROUND: Adipokines, as well as the fatty acid profile of red blood cell (RBC) membranes, are known to play important roles in the development and progression of metabolic complications induced by obesity. Thus, the objective of this study is to compare the serum adipokine profile and the RBC membrane fatty acid profile of normal-weight and obese adults, and to analyze their relationship with serum biochemical parameters. METHODS: An observational case-control study was performed in 75 normal-weight and obese adult subjects. Biochemical serum parameters, eight serum adipokines and the RBC membrane fatty acid profiles were measured. Associations between parameters were established using regression analysis. RESULTS: Subjects with obesity showed increased levels of leptin, fibroblast growth factor 21 (FGF21) and overexpressed nephroblastoma (NOV/CCN3), decreased adiponectin, and similar levels of vaspin and chemerin compared to normal-weight subjects. Significant positive and negative correlations were found with triglycerides and high-density lipoprotein-cholesterol (HDL-c), respectively. An increase in the total ω-6 fatty acids in the RBC membrane fatty acid profiles in subjects with obesity was observed, because of higher levels of both dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), and decreased total ω-3 fatty acids, mainly due to lower levels of docosahexaenoic acid (DHA). The ω-6/ω-3 ratio in the RBCs was significantly higher, suggesting an inflammatory status, as was also suggested by a reduced adiponectin level. A negative association between DGLA and adiponectin, and a positive association between DHA and serum triglycerides, was observed. CONCLUSIONS: Important alterations in serum adipokine and RBC fatty acid profiles are found in subjects with obesity.

13.
Pharmacol Res ; 65(6): 577-83, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22449789

RESUMO

Previous epidemiological and feeding studies have observed that adherence to Mediterranean diet (Med-Diet) is associated with reduced cardiovascular risk. However, the molecular mechanisms involved are not fully understood. Since atherosclerosis is nowadays considered a low-grade inflammatory disease, recent studies have explored the anti-inflammatory effects of a Med-Diet intervention on serum and cellular biomarkers related to atherosclerosis. In two sub-studies of the PREDIMED (PREvencion con DIeta MEDiterranea) trial, we analyzed the effects at 3 months of two Med-Diet interventions supplemented with either virgin olive oil (VOO) or nuts compared with a control low-fat diet (LFD). Both Med-Diets showed an anti-inflammatory effect reducing serum C-reactive protein, interleukin-6 (IL6) and endothelial and monocytary adhesion molecules and chemokines (P<0.05; all), whereas these parameters increased after the LFD intervention (P<0.05; all). In another substudy, we evaluated the long-term (1 year) effects of these interventions on vascular risk factors in 516 high-risk subjects, as well as the effect of different Med-Diet components in the reduction of these biomarkers. At 1 year, the Med-Diet groups had significant decreases in the plasma concentrations of IL6, tumor necrosis factor receptor (TNFR) 60 and TNFR80 (P<0.05), while intercellular adhesion molecule 1 (ICAM-1), TNFR60 and TNFR80 concentrations increased in the LFD group (P<0.002). In addition, those allocated in the highest tertile of VOO and vegetables consumption had a significant diminution of plasma TNFR60 concentration compared with those in tertile 1 (P<0.02). In conclusion, Med-Diet exerts an anti-inflammatory effect on cardiovascular system since it down-regulates cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high cardiovascular risk.


Assuntos
Aterosclerose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Mediadores da Inflamação/sangue , Inflamação/prevenção & controle , Nozes , Óleos de Plantas , Animais , Aterosclerose/epidemiologia , Aterosclerose/imunologia , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/imunologia , Humanos , Inflamação/epidemiologia , Inflamação/imunologia , Azeite de Oliva , Medição de Risco , Fatores de Risco
14.
Surg Oncol ; 44: 101823, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36041377

RESUMO

BACKGROUND: Targeted axillary dissection, which combines sentinel lymph node biopsy with removal of the proven involved node noted during the staging process, has been shown to improve axillary staging and decrease false negative rates after neoadjuvant chemotherapy in patients with breast cancer. OBJECTIVE(S): The main goal of this study was to assess the ability to identify and remove the clipped node and the false negative rate of targeted axillary dissection. METHODS: We performed a prospective study among patients with biopsy-confirmed nodal metastases who received neoadjuvant chemotherapy. A clip was placed on the sample node prior systemic therapy. After neoadjuvant chemotherapy, all patients underwent sentinel lymph node biopsy (dual tracer), localization and excision of the clipped node and axillary lymph node dissection. The clipped node was preoperatively localized in all cases placing an iodine-125 seed guided by ultrasound. The pathology of the sentinel nodes and clipped node was compared with other nodes. RESULTS: A total of 455 patients with invasive breast cancer were studied. Of the 148 patients with NAC, 32 met the eligibility criteria and were enrolled in the study. Mean age at diagnosis was 52.3 years. Systematic lymphadenectomy was performed in all patients, with an average of 14.3 lymph nodes removed. Detection rate of the clipped node alone was 96.9%, and 100% for targeted axillary dissection. Ability of clipped node alone to predict nodal status showed a FNR of 10,5% while SLNB alone performed by dual tracer and targeted axillary dissection, showed FNRs of 5.3% and 5.0%, respectively. Sentinel lymph nodes matched clipped node in 23 patients (74.2%). CONCLUSION (S): In node positive breast cancer patients, targeted axillary dissection is a reliably approach for axillary staging after neoadjuvant chemotherapy. The preoperative location of the clipped node is mandatory to increase the detection rate and optimize the results of the technique.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Estudos Prospectivos , Biópsia de Linfonodo Sentinela/métodos
15.
J Pers Med ; 11(5)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922764

RESUMO

Metabolically healthy obesity (MHO) has been described as BMI ≥ 30 kg/m2, without metabolic disorders traditionally associated with obesity. Beyond this definition, a standardized criterion, for adults and children, has not been established yet to explain the absence of those metabolic disorders. In this context, biomarkers of inflammation have been proposed as suitable candidates to describe MHO. The use of mature red blood cell fatty acid (RBC FA) profile is here proposed since its membrane lipidome includes biomarkers of pro- and anti-inflammatory conditions with a strict relationship with metabolic and nutritional status. An observational study was carried out in 194 children (76 children with obesity and 118 children with normal weight) between 6 and 16 years old. RBC FAs were analyzed by gas chromatography-flame ionization detector (GC-FID). An unsupervised hierarchical clustering method was conducted on children with obesity, based on the RBC FA profile, to isolate the MHO cluster. The MHO cluster showed FA levels similar to children with normal weight, characterized by lower values of arachidonic acid, (total ω-6 FA, ω6/ω3 FA ratios and higher values for EPA, DHA, and total ω-3 FA) (for all of them p ≤ 0.01) compared to the rest of the children with obesity (obese cluster). The MHO cluster also presented lipid indexes for higher desaturase enzymatic activity and lower SFA/MUFA ratio compared to the obese cluster. These differences are relevant for the follow-up of patients, also in view of personalized protocols providing tailored nutritional recommendations for the essential fatty acid intakes.

16.
Cells ; 10(10)2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34685541

RESUMO

During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for CDC5 gene expression. Previous work revealed that overexpression of CDC5 partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective zip1Δ mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-ΔN70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the zip1Δ-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the zip1Δ single mutant, the zip1Δ cdc5-ΔN70 double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a CDC5-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control.


Assuntos
Pontos de Checagem do Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Regulação para Baixo , Meiose , Quinase 1 Polo-Like
17.
Metabolites ; 11(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33435565

RESUMO

As the obesity epidemic continues to grow inexorably worldwide, the need to develop effective strategies to prevent and control obesity seems crucial. The use of molecular tools can be useful to characterize different obesity phenotypes to provide more precise nutritional recommendations. This study aimed to determine the fatty acid (FA) profile of red blood cell (RBC) membranes, together with the evaluation of their dietary intake and biochemical parameters, of children and adults with obesity. An observational study was carried out on 196 children (113 with normal weight and 83 with obesity) and 91 adults (30 with normal weight and 61 with obesity). Mature RBC membrane phospholipids were analyzed for FA composition by gas chromatography-mass spectrometry (GC-MS). Dietary habits were evaluated using validated food frequency questionnaires (FFQ). Children with obesity presented higher levels of ω-6 polyunsaturated FAs (mainly linoleic acid, p = 0.01) and lower values of ω-3 FAs (mainly DHA, p < 0.001) compared with adults. Regarding blood biochemical parameters, children with obesity presented lower levels of glucose, LDL cholesterol, and alanine aminotransferase compared with adults with obesity. These lipidomic differences could be considered to provide specific nutritional recommendations for different age groups, based on an adequate fat intake.

18.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31109904

RESUMO

INTRODUCTION: Ethnic differences have been studied previously in schizophrenia and first episodes of psychosis (FEP). Previous studies in Netherlands have reported a higher incidence of psychosis in male Moroccan immigrants and more clinical severity. However there is lack of studies in Spain with morocco population and FEP. OBJECTIVES: This study aims to determine the clinical differences in a sample of FEP between Morocco and Spanish population, recruited in a hospitalisation unit. MATERIAL AND METHODS: Descriptive and cross-sectional study of 83 inpatients (FEP). Functionality and symptomatology were evaluated at entry and discharge, the pattern of use of cannabis was evaluated at entry, the dose of antipsychotic and the pattern of side-effects at discharge. Comparisons between native-born population and Morocco population was made with univariate analysis and logistic regression was made for evaluating the independence of the associations. RESULTS: The 28.9% of the sample was Morocco group. No significance differences were found in clinical characteristics between groups at entry or at discharge. Compared with native-born, the Morocco group were more male, with less years of education, worse functionality, reported less use of cannabis, a better pattern of side effects and a tendency of more prescription of LAis. After the multivariate analysis, just remains a lower functionality (OR 0.93; IC 95%: 0.88-0.99, P=0.02) and lower years of education (OR 0.75; IC 95%: 0.56-1.01, P=0.05), remain significative with being related with Morocco origin. CONCLUSIONS: Our study provides evidence for ethnic differences in Morocco population with FEP. Patients with Morocco ethnicity have more probability of being males, less years of educations. Have lower functionality and a better profile of side effects.

19.
Nutrients ; 12(8)2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32718098

RESUMO

There is extensive information of the beneficial effects of virgin olive oil (VOO), especially on cardiovascular diseases. Some VOO healthy properties have been attributed to their phenolic-compounds (PCs). The aim of this review is to present updated data on the effects of olive oil (OO) PCs on the gut microbiota, lipid metabolism, immune system, and obesity, as well as on the crosstalk among them. We summarize experiments and clinical trials which assessed the specific effects of the olive oil phenolic-compounds (OOPCs) without the synergy with OO-fats. Several studies have demonstrated that OOPC consumption increases Bacteroidetes and/or reduces the Firmicutes/Bacteroidetes ratio, which have both been related to atheroprotection. OOPCs also increase certain beneficial bacteria and gut-bacteria diversity which can be therapeutic for lipid-immune disorders and obesity. Furthermore, some of the mechanisms implicated in the crosstalk between OOPCs and these disorders include antimicrobial-activity, cholesterol microbial metabolism, and metabolites produced by bacteria. Specifically, OOPCs modulate short-chain fatty-acids produced by gut-microbiota, which can affect cholesterol metabolism and the immune system, and may play a role in weight gain through promoting satiety. Since data in humans are scarce, there is a necessity for more clinical trials designed to assess the specific role of the OOPCs in this crosstalk.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Azeite de Oliva/farmacologia , Fenóis/farmacologia , Doenças Cardiovasculares/prevenção & controle , Colesterol , Humanos , Lipídeos , Azeite de Oliva/química
20.
Eur Neuropsychopharmacol ; 36: 235-243, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32291209

RESUMO

There is a scarcity of studies investigating the effect of sex on the clinical and treatment characteristics of first-admitted patients with first-episode psychosis (FEP). The reasons for using cannabis and the effect of cannabis on clinical features have not received enough attention either. We aim therefore, to investigate sex differences in the reasons for cannabis use and to determine the effects of sex, cannabis use and their interaction on clinical variables at admission and at discharge from the inpatient unit. 204 first-admitted FEPs in two inpatient units in Spain were included. The reasons for using cannabis were determined using the Dixon questionnaire. Clinical variables were compared between sexes and between cannabis users and non-users. Cannabis use was more frequent in males, but females were more likely to smoke cannabis to "feel relaxed". There was a main effect of sex on positive psychotic symptoms and antipsychotics dose and an interaction effect of cannabis and sex on global functioning at discharge .Our findings show sex differences in the reasons for cannabis use and in some clinical and treatment characteristics among FEP patients. More studies focusing on gender perspectives are needed to develop more individualized treatments.


Assuntos
Uso da Maconha/psicologia , Uso da Maconha/tendências , Admissão do Paciente/tendências , Transtornos Psicóticos/psicologia , Caracteres Sexuais , Adolescente , Adulto , Estudos Transversais , Feminino , Alucinógenos/efeitos adversos , Humanos , Masculino , Uso da Maconha/efeitos adversos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Adulto Jovem
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