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1.
ACS Chem Biol ; 19(7): 1626-1637, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39026469

RESUMO

Chronic pain is a prevalent problem that plagues modern society, and better understanding its mechanisms is critical for developing effective therapeutics. Nerve growth factor (NGF) and its primary receptor, Tropomyosin receptor kinase A (TrkA), are known to be potent mediators of chronic pain, but there is a lack of established methods for precisely perturbing the NGF/TrkA signaling pathway in the study of pain and nociception. Optobiological tools that leverage light-induced protein-protein interactions allow for precise spatial and temporal control of receptor signaling. Previously, our lab reported a blue light-activated version of TrkA generated using light-induced dimerization of the intracellular TrkA domain, opto-iTrkA. In this work, we show that opto-iTrkA activation is able to activate endogenous ERK and Akt signaling pathways and causes the retrograde transduction of phospho-ERK signals in dorsal root ganglion (DRG) neurons. Opto-iTrkA activation also sensitizes the transient receptor potential vanilloid 1 (TRPV1) channel in cellular models, further corroborating the physiological relevance of the optobiological stimulus. Finally, we show that opto-iTrkA enables light-inducible potentiation of mechanical sensitization in mice. Light illumination enables nontraumatic and reversible (<2 days) sensitization of mechanical pain in mice transduced with opto-iTrkA, which provides a platform for dissecting TrkA pathways for nociception in vitro and in vivo.


Assuntos
Dor Crônica , Gânglios Espinais , Luz , Receptor trkA , Animais , Receptor trkA/metabolismo , Dor Crônica/metabolismo , Camundongos , Gânglios Espinais/metabolismo , Canais de Cátion TRPV/metabolismo , Humanos , Transdução de Sinais , Camundongos Endogâmicos C57BL , Masculino , Fator de Crescimento Neural/metabolismo , Neurônios/metabolismo
4.
Int J Biol Macromol ; 275(Pt 2): 133740, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986986

RESUMO

Coffee beverage is a source of dietary fiber composed by arabinogalactans, which can also be associated to proteins and phenolic compounds, originating melanoidins. Human colonic in vitro fermentations of coffee fractions, one rich in melanoidins (Mel) and the other in its parental polysaccharide arabinogalactans (AG), were performed in order to evaluate the metabolites produced by microbiota, namely short-chain fatty acids (SCFA), phenolic compounds, and bile acids. After 48 h of fermentation, a higher fermentability of the carbohydrate fraction of AG (62 %) than that of Mel (27 %) was observed, resulting in a SCFA content of 63 mM and 22 mM, respectively. Supplementation with AG and Mel fractions decreased the acetate:propionate ratio from 4.7 (in the absence of coffee fractions) to 2.5 and 3.5, respectively, suggesting a potential inhibition of HMG-CoA reductase, a rate-limiting enzyme for cholesterol synthesis. The fermentation of coffee fractions yielded dihydroferulic and dihydrocaffeic acids, known to have antioxidant properties. In the presence of Mel, it was observed a decrease (from 0.25 to 0.16 mg/mL) in the production of secondary bile acids, whose high content is associated to the development of several diseases, such as colorectal cancer, neurodegenerative and cardiovascular.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39015193

RESUMO

Objective: . Acute myocardial infarction-related cardiogenic shock (AMI-CS) is often accompanied by tachycardia, which, in turn, increases myocardial oxygen consumption and hinders the use of ventricular assist devices, such as intra-aortic balloon pump. Evidence suggests that ivabradine may reduce heart rate (HR) without affecting other hemodynamic parameters. The aim of the present study was to determine the effect of ivabradine on reducing HR and changes in other hemodynamic parameters such as cardiac index (CI), in patients with AMI-CS and tachycardia. Materials and methods: . A single-center, open label, randomized clinical trial included patients diagnosed with AMI-CS and tachycardia with >100 beats per minute (BPM). Heart rate, cardiac index, and other hemodynamic parameters measured by pulmonary flotation catheter were compared at 0, 6, 12, 24, and 48 hours after randomization. Results: . A total of 12 patients were randomized; 6 received standard therapy, and 6 received ivabradine in addition to standard therapy. Baseline clinical characteristics were similar at randomization. A statistically significant lower heart rate was found at 12 hours (p=0.003) and 48 hours (p=0.029) after randomization, with differences of -23.3 (-8.2 to -38.4) BPM and -12.6 (-0.5 to -25.9) BPM, respectively. No differences in cardiac index, or any other evaluated hemodynamic parameters, length of hospital stay, nor mortality rate were noted between both groups. Conclusions: . The use of ivabradine in patients with AMI-CS was associated with a significant reduction in heart rate at 12 and 48 h, without affecting other hemodynamic parameters.


Objetivo: . El choque cardiogénico relacionado con el infarto agudo de miocardio (AMI-CS, por sus siglas en inglés) suele ir acompañado de taquicardia, lo que, a su vez, aumenta el consumo de oxígeno miocárdico y dificulta el uso de dispositivos de asistencia ventricular, como la bomba de balón intraaórtico. La evidencia sugiere que la ivabradina puede reducir la frecuencia cardíaca (FC) sin afectar otros parámetros hemodinámicos. El objetivo del presente estudio fue determinar el efecto de la ivabradina en la reducción de la FC y los cambios en otros parámetros hemodinámicos como el índice cardíaco (CI) en pacientes con AMI-CS y taquicardia. Materiales y métodos: Se incluyeron pacientes diagnosticados con AMI-CS y taquicardia con >100 latidos por minuto (LPM) en un ensayo clínico aleatorizado de un solo centro. La frecuencia cardíaca, el índice cardíaco y otros parámetros hemodinámicos medidos mediante catéter de flotación pulmonar se compararon a las 0, 6, 12, 24 y 48 h después de la aleatorización. Resultados: Se aleatorizaron un total de 12 pacientes; 6 recibieron terapia estándar y 6 recibieron ivabradina además de la terapia estándar. Las características clínicas basales fueron similares en la aleatorización. Se encontró una frecuencia cardíaca significativamente más baja a las 12 h (p=0,003) y a las 48 h (p=0,029) después de la aleatorización, con diferencias de -23,3 (-8,2 a -38,4) LPM y -12,6 (-0,5 a -25,9) LPM, respectivamente. No se observaron diferencias en el índice cardíaco, en ningún otro parámetro hemodinámico evaluado; tampoco en la duración de la estancia hospitalaria, ni en la tasa de mortalidad entre ambos grupos. Conclusiones: El uso de ivabradina en pacientes con AMI-CS se asoció con una reducción significativa en la frecuencia cardíaca a las 12 y 48 h, sin afectar otros parámetros hemodinámicos.

7.
Physiol Plant ; 176(4): e14438, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39054574

RESUMO

Human mitochondria contain a molybdoprotein capable of reducing amidoximes using cytochrome b5/cytochrome b5 reductase (Cb/CbR). This 'amidoxime reducing component' (ARC) also reduces nitrite to nitric oxide (NO). In the plant kingdom, distinct functions have been suggested for ARCs. Thus, the single ARC of Chlamydomonas reinhardtii (crARC) reduces nitrite to NO by taking electrons from nitrate reductase (NR). Therefore, it was proposed that a dual NR/crARC system can generate NO under physiological conditions and the crARC was renamed to 'NO-forming nitrite reductase' (NOFNiR). In contrast to this, the two ARC enzymes from Arabidopsis thaliana were not found to produce NO in vitro at physiological nitrite concentrations, suggesting a different, as yet unknown, function in vascular plants. Here, we have investigated the two ARCs of Lotus japonicus (LjARCs) to shed light on this controversy and to examine, for the first time, the distribution of ARCs in plant tissues. The LjARCs are localized in the cytosol and their activities and catalytic efficiencies, which are much higher than those of A. thaliana, are consistent with a role as NOFNiR. LjARCs are prone to S-nitrosylation in vitro by S-nitrosoglutathione and this post-translational modification drastically inhibits their activities. The enzymes are mainly expressed in flowers, seeds and pods, but are absent in nodules. LjARCs are active with NR and Cb/CbR as electron-transferring systems. However, the LjNR mRNA levels in seeds and pods are negligible, whereas our proteomic analyses show that pods contain the two ARCs, Cb and CbR. We conclude that LjARCs may play a role as NOFNiR by receiving electrons from the Cb/CbR system but do not act in combination with NR.


Assuntos
Lotus , Óxido Nítrico , Nitrito Redutases , Proteínas de Plantas , Lotus/genética , Lotus/enzimologia , Lotus/metabolismo , Óxido Nítrico/metabolismo , Nitrito Redutases/metabolismo , Nitrito Redutases/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Nitritos/metabolismo , Oxirredução
8.
Mol Cell Proteomics ; : 100818, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39047911

RESUMO

Candida albicans is a diploid pathogen known for its ability to live as a commensal fungus in healthy individuals, but causing both superficial infections and disseminated candidiasis in immunocompromised patients where it is associated with high morbidity and mortality. Its success in colonizing the human host is attributed to a wide range of virulence traits that modulate interactions between the host and the pathogen, such as optimal growth rate at 37 ºC, the ability to switch between yeast and hyphal forms and a remarkable genomic and phenotypic plasticity. A fascinating aspect of its biology is a prominent heterogeneous proteome that arises from frequent genomic rearrangements, high allelic variation, and high levels of amino acid misincorporations in proteins. This leads to increased morphological and physiological phenotypic diversity of high adaptive potential, but the scope of such protein mistranslation is poorly understood due to technical difficulties in detecting and quantifying amino acid misincorporation events in complex protein samples. We have developed and optimized mass spectrometry and bioinformatics pipelines capable of identifying rare amino acid misincorporation events at the proteome level. We have also analysed the proteomic profile of an engineered C. albicans strain that exhibits high level of leucine misincorporation at protein CUG sites and employed an in vivo quantitative gain-of-function fluorescence reporter system to validate our LC-MS/MS data. C. albicans misincorporates amino acids above the background level at protein sites of diverse codons, particularly at CUG, confirming our previous data on the quantification of leucine incorporation at single CUG sites of recombinant reporter proteins, but increasing misincorporation of Leucine at these sites does not alter the translational fidelity of the other codons. These findings indicate that the C. albicans statistical proteome exceeds prior estimates, suggesting that its highly plastic phenome may also be modulated by environmental factors due to translational ambiguity.

9.
Hum Genomics ; 18(1): 75, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956648

RESUMO

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.


Assuntos
Envelhecimento Cognitivo , Metilação de DNA , Estudo de Associação Genômica Ampla , Herança Multifatorial , Humanos , Metilação de DNA/genética , Feminino , Masculino , Herança Multifatorial/genética , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Fatores de Risco , Imageamento por Ressonância Magnética , Envelhecimento/genética , Envelhecimento/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Estratificação de Risco Genético
10.
Eur J Sport Sci ; 24(7): 1021-1031, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38956790

RESUMO

The aims of this study were to assess (i) the load-velocity relationship during the box squat exercise in women survivors of breast cancer, (ii) which velocity variable (mean velocity [MV], mean propulsive velocity [MPV], or peak velocity [PV]) shows stronger relationship with the relative load (%1RM), and (iii) which regression model (linear [LA] or polynomic [PA]) provides a greater fit for predicting the velocities associated with each %1RM. Nineteen women survivors of breast cancer (age: 53.2 ± 6.9 years, weight: 70.9 ± 13.1 kg, and height: 163.5 ± 7.4 cm) completed an incremental load test up to one-repetition maximum in the box squat exercise. The MV, MPV, and the PV were measured during the concentric phase of each repetition with a linear velocity transducer. These measurements were analyzed by regression models using LA and PA. Strong correlations of MV with %1RM (R2 = 0.903/0.904; the standard error of the estimate (SEE) = 0.05 m.s-1 by LA/PA) and MPV (R2 = 0.900; SEE = 0.06 m.s-1 by LA and PA) were observed. In contrast, PV showed a weaker association with %1RM (R2 = 0.704; SEE = 0.15 m.s-1 by LA and PA). The MV and MPV of 1RM was 0.22 ± 0.04 m·s-1, whereas the PV at 1RM was 0.63 ± 0.18 m.s-1. These findings suggest that the use of MV to prescribe relative loads during resistance training, as well as LA and PA regression models, accurately predicted velocities for each %1RM. Assessing and prescribing resistance exercises during breast cancer rehabilitation can be facilitated through the monitoring of movement velocity.


Assuntos
Neoplasias da Mama , Treinamento Resistido , Humanos , Feminino , Neoplasias da Mama/reabilitação , Pessoa de Meia-Idade , Força Muscular/fisiologia , Adulto , Sobreviventes de Câncer , Terapia por Exercício/métodos
11.
Redox Biol ; 75: 103211, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38908072

RESUMO

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells' susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with - or caused by - ferroptosis.

12.
Carbohydr Polym ; 339: 122268, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823931

RESUMO

The influence of locust bean gum (LBG) galactomannans (GMs) molecular weight (Mw) to assemble microparticulate systems was evaluated, and carriers for deep lung delivery were developed. A commercial batch of LBG with a mannose/galactose (M/G) ratio of 2.4 (batch 1) was used to study the influence of different microwave partial acid hydrolysis conditions on carbohydrate composition, glycosidic linkages, and aqueous solutions viscosity. The microwave treatment did not affect the composition, presenting 4-Man (36-42 %), 4,6-Man (27-35 %), and T-Gal (24-25 %) as the main glycosidic linkages. Depolymerization led to a viscosity reduction (≤0.005 Pa·s) with no major impact on polysaccharide debranching. The structural composition of the LBG galactomannans were further elucidated with sequence-specific proteins using carbohydrate microarray technologies. A second batch of LBG (M/G 3.3) was used to study the impact of GMs with different Mw on microparticle assembling, characteristics, and insulin release kinetics. The low-Mw GMs microparticles led to a faster release (20 min) than the higher-Mw (40 min) ones, impacting the release kinetics. All microparticles exhibited a safety profile to cells of the respiratory tract. However, only the higher-Mw GMs allowed the assembly of microparticles with sizes suitable for this type of administration.


Assuntos
Galactose , Mananas , Peso Molecular , Gomas Vegetais , Mananas/química , Galactose/química , Galactose/análogos & derivados , Gomas Vegetais/química , Humanos , Pulmão/metabolismo , Portadores de Fármacos/química , Tamanho da Partícula , Viscosidade , Insulina/química , Insulina/administração & dosagem , Liberação Controlada de Fármacos , Galactanos/química , Manose/química , Animais
13.
Sci Data ; 11(1): 601, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849407

RESUMO

Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts.


Assuntos
Invertebrados , Rios , Animais , Europa (Continente) , Água Doce , Dinâmica Populacional , Qualidade da Água , Biodiversidade , Ecossistema
14.
Cell ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38878778

RESUMO

Inflammation-induced neurodegeneration is a defining feature of multiple sclerosis (MS), yet the underlying mechanisms remain unclear. By dissecting the neuronal inflammatory stress response, we discovered that neurons in MS and its mouse model induce the stimulator of interferon genes (STING). However, activation of neuronal STING requires its detachment from the stromal interaction molecule 1 (STIM1), a process triggered by glutamate excitotoxicity. This detachment initiates non-canonical STING signaling, which leads to autophagic degradation of glutathione peroxidase 4 (GPX4), essential for neuronal redox homeostasis and thereby inducing ferroptosis. Both genetic and pharmacological interventions that target STING in neurons protect against inflammation-induced neurodegeneration. Our findings position STING as a central regulator of the detrimental neuronal inflammatory stress response, integrating inflammation with glutamate signaling to cause neuronal cell death, and present it as a tractable target for treating neurodegeneration in MS.

15.
Materials (Basel) ; 17(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38930318

RESUMO

Cancer is a major worldwide public health problem. Although there have already been astonishing advances in cancer diagnosis and treatment, the scientific community continues to make huge efforts to develop new methods to treat cancer. The main objective of this work is to prepare, using a green sol-gel method with coconut water powder (CWP), a new nanocomposite with a mixture of Gd3Fe5O12 and ZnFe2O4, which has never been synthesized previously. Therefore, we carried out a structural (DTA-TG and X-ray diffraction), morphological (SEM), and magnetic (VSM and hyperthermia) characterization of the prepared samples. The prepared nanocomposite denoted a saturation magnetization of 11.56 emu/g at room temperature with a ferromagnetic behavior and with a specific absorption rate (SAR) value of 0.5 ± 0.2 (W/g). Regarding cytotoxicity, for concentrations < 10 mg/mL, it does not appear to be toxic. Although the obtained results were interesting, the high particle size was identified as a problem for the use of this nanocomposite.

16.
Molecules ; 29(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38930795

RESUMO

The need to transition from fossil fuels to renewables arises from factors such as depletion, price fluctuations, and environmental considerations. Lignocellulosic biomass, being abundant, and quickly renewable, and not interfering with food supplies, offers a standout alternative for chemical production. This paper explores the energetic characteristics of two derivatives of furfural-a versatile chemical obtained from biomass with great potential for commercial sustainable chemical and fuel production. The standard (p° = 0.1 MPa) molar enthalpies of formation of the liquids furfurylamine and 5-methylfurfurylamine were derived from the standard molar energies of combustion, determined in oxygen and at T = 298.15 K, by static bomb combustion calorimetry. Their standard molar enthalpies of vaporization were also determined at the same temperature using high-temperature Calvet microcalorimetry. By combining these data, the gas-phase enthalpies of formation at T = 298.15 K were calculated as -(43.5 ± 1.4) kJ·mol-1 for furfurylamine, and -(81.2 ± 1.7) kJ·mol-1 for 5-methylfurfurylamine. Furthermore, a theoretical analysis using G3 level calculations was performed, comparing the calculated enthalpies of formation with the experimental values to validate both results. This method has been successfully applied to similar molecules. The discussion looks into substituent effects in terms of stability and compares them with similar compounds.

17.
Nutrients ; 16(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38931300

RESUMO

The main objective of this work is to investigate the relationship between the Mediterranean diet (MD) and metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary objective is to analyze sex differences. METHODS: A cross-sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, and a total of 3417 subjects with a mean age ± SD of 60.14 ± 9.14 years (57% men) were included. We followed the five criteria established in the National Cholesterol Education Program III to define MetS. The MD was assessed with the 14-item Mediterranean diet adherence screener (MEDAS) used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. RESULTS: The mean ± SD value of the MEDAS questionnaire was 5.83 ± 2.04 (men 5.66 ± 2.06 and women 6.04 ± 1.99; p < 0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p < 0.001). MetS was observed in 41.6% (39.0% men and 45.2% women; p < 0.001). In the multiple regression analysis, after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (ß = -0.336), and with the different components of MetS: systolic blood pressure (ß = -0.011), diastolic blood pressure (ß = -0.029), glycemia (ß = -0.009), triglycerides (ß = -0.004), and waist circumference (ß = -0.026), except with the HDL-cholesterol value which showed a positive association (ß = 0.021); p < 0.001 in all cases. In the logistic regression analysis performed, we found that an increase in MD adherence was associated with a decrease in the probability of MetS (OR = 0.56) and its components: blood pressure levels ≥ 130/85 mmHg (OR = 0.63), fasting plasma glucose ≥ 100 mg/dL (OR = 0.62), triglyceride levels ≥ 150 mg/dL (OR = 0.65), waist circumference levels ≥ 88 cm in women and ≥102 cm in men (OR = 0.74), and increased high-density lipoprotein cholesterol < 40 mg/dL in men and <50 mg/dL in women (OR = 1.70); p < 0.001 in all cases. The results by sex were similar, both in multiple regression and logistic regression. CONCLUSIONS: The results found in our work indicate that the greater the adherence to the MD, the lower the probability of presenting MetS. This result is repeated in the study by sex. More studies are needed to clarify that these results can be extended to the rest of the Mediterranean countries, and to other countries outside the Mediterranean basin.


Assuntos
Dieta Mediterrânea , Síndrome Metabólica , População Branca , Humanos , Dieta Mediterrânea/estatística & dados numéricos , Síndrome Metabólica/epidemiologia , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Idoso , Adulto , Fatores Sexuais , Circunferência da Cintura , Inquéritos e Questionários , Pressão Sanguínea , Triglicerídeos/sangue , Glicemia/metabolismo
18.
Viruses ; 16(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38932111

RESUMO

Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral rotavirus vaccines in young children may be affected by significant immunological differences between individuals in early life and adults. Therefore, understanding the dynamics of early-life systemic and mucosal immune responses and the factors that affect them is essential to improve the current rotavirus vaccines and develop the next generation of mucosal vaccines. This review focuses on the advances in T-cell development during early life in mice and humans, discussing how immune homeostasis and response to pathogens is established in this period compared to adults. Finally, the review explores how this knowledge of early-life T-cell immunity could be utilized to enhance current and novel rotavirus vaccines.


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Linfócitos T , Vacinas contra Rotavirus/imunologia , Vacinas contra Rotavirus/administração & dosagem , Humanos , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/imunologia , Animais , Rotavirus/imunologia , Linfócitos T/imunologia , Administração Oral , Imunidade nas Mucosas , Camundongos
19.
Nat Commun ; 15(1): 5263, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898130

RESUMO

Most fine ambient particulate matter (PM2.5)-based epidemiological models use globalized concentration-response (CR) functions assuming that the toxicity of PM2.5 is solely mass-dependent without considering its chemical composition. Although oxidative potential (OP) has emerged as an alternate metric of PM2.5 toxicity, the association between PM2.5 mass and OP on a large spatial extent has not been investigated. In this study, we evaluate this relationship using 385 PM2.5 samples collected from 14 different sites across 4 different continents and using 5 different OP (and cytotoxicity) endpoints. Our results show that the relationship between PM2.5 mass vs. OP (and cytotoxicity) is largely non-linear due to significant differences in the intrinsic toxicity, resulting from a spatially heterogeneous chemical composition of PM2.5. These results emphasize the need to develop localized CR functions incorporating other measures of PM2.5 properties (e.g., OP) to better predict the PM2.5-attributed health burdens.


Assuntos
Poluentes Atmosféricos , Material Particulado , Material Particulado/toxicidade , Humanos , Poluentes Atmosféricos/toxicidade , Oxirredução , Tamanho da Partícula , Monitoramento Ambiental/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos
20.
Oncol Res Treat ; : 1-9, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38870920

RESUMO

INTRODUCTION: Stomach cancer is one of the most common causes of cancer worldwide, especially in the population over 65 years. The survival rate of the elderly is lower in comparison with young people, and they are underrepresented in clinical trials and research in general. The evaluation of Multidimensional Geriatric Assessment (MGA) would be key for assessing the prognosis of these patients and therefore having a more informed decision-making process when considering one of the most vulnerable populations. METHODS: A search was performed in the OVID, Embase, and PubBMed databases. There was no restriction on publication time, language, or study design. Eligible studies were those that included geriatric patients with a diagnosis of nonmetastatic stomach cancer who receive oncospecific and surgical management, used Multidimensional/Comprehensive Geriatric Assessment (MGA), and which outcomes included at least overall survival, morbidity, and mortality. RESULTS: Four studies were included, and the MGA battery was not implemented, but rather easily measurable scales such as nutritional status, functional status, cognitive and behavioral disorders, comorbidities, and polypharmacy. Some authors proposed that the assessment of overall survival is not explicit among the included studies; patients with gastric cancer and mild, moderate, severe, and total dependence had higher mortality than independent patients (39% [HR 1.39; 95% CI: 1.09-1.7], 68% [95% CI: 1.46-1.93], 187% [HR 2.87 95% CI: 2.47-3.34], and 234% [95% CI: 2.81-3.97]), respectively. The Zhou study showed an association between sarcopenia, assessed by imaging studies, and a longer hospital stay in days (16 [9] vs. 13 [6], p 0.004). The study by Pujara found that polypharmacy (OR 2.36 CI: 1.08-5.17) and weight loss greater than 10% in the past 6 months were associated with greater postoperative morbidity at 90 days (OR 2.36 CI: 1.08-5.17, OR 11.21 CI: 2.16-58.24). CONCLUSION: MGA was not broadly implemented. Geriatric assessment dependency appears to be a prognostic marker of survival in patients with gastric cancer. Sarcopenia appears to be an important prognostic marker for short- and long-term outcomes. Higher quality studies in this specific population are required to support the systematic use of this assessment for the choice of appropriate therapy according to the patient.

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