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1.
Handb Exp Pharmacol ; 268: 471-486, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34085122

RESUMO

In the western world the prevalence of atopic diseases such as food allergies is increasing highly significantly. One of the earliest and most prevalent food allergies occurring in the first year of life is cow's milk allergy. No treatment is available and only avoidance of the cow's milk allergens prevents the occurrence of an allergic reaction. Since cow's milk allergic children have an increased risk of developing other allergies later in life, investigating nutritional strategies to prevent the development of cow's milk allergy by developing oral tolerance is of high interest. Nutritional components such as prebiotics, probiotics, synbiotics and long-chain polyunsaturated fatty acids possess potential to support the maturation of the immune system early in life that might prevent the development of cow's milk allergy. The available research, so far, shows promising results particularly on the development of eczema. However, the preventive effects of the nutritional interventions on the development of food allergy are inconclusive. Future research may benefit from the combination of various dietary components. To clarify the preventive effects of the nutritional components in food allergy more randomized clinical trials are needed.


Assuntos
Hipersensibilidade Alimentar , Hipersensibilidade a Leite , Probióticos , Animais , Bovinos , Dieta , Feminino , Hipersensibilidade a Leite/prevenção & controle , Prevalência
2.
Psychol Res Behav Manag ; 14: 1947-1957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887688

RESUMO

Purpose: The aim of this study was to evaluate whether or not living alone or together throughout the lockdown had an impact on mood, perceived immune fitness, as well as the presence and severity of COVID-19 symptoms. Methods: N = 505 participants completed an online survey, which included questions on living situations, as well as mood, perceived immune fitness and COVID-19 symptom presence and severity. These factors were assessed retrospectively for the time periods before and during the COVID-19 pandemic. Results: An overall decrease in mood was observed for both those living alone and together during the lockdown period. However, significantly larger increases in feelings of loneliness were observed for the group living alone. Furthermore, both groups reported decreases in perceived immune fitness, whereas only the group living alone reported a significant increase in COVID-19 symptom presence and severity. Moreover, significant correlations were found between perceived immune fitness, anxiety, and loneliness. These correlations were strongest in the group living alone. Lastly, positive correlations were found between perceived immune fitness and mood outcomes with being active, optimistic and the ability to cope with stress. Increased optimism, being more active and the adequate ability to cope with stress were associated with a reduced negative impact on perceived immune fitness. Conclusion: The first COVID-19 lockdown period in the Netherlands was a challenging period for both people who lived alone and those living together, resulting in decreases in mood and poorer perceived immune fitness. Those living alone were, however, more heavily impacted by the lockdown restrictions. This was further reflected by the increased presence and severity of COVID-19 symptoms in people who lived alone during the first COVID-19 lockdown in The Netherlands.

3.
Front Immunol ; 12: 780453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925358

RESUMO

Background: Tuberculous pleural effusion (TPE) is one of the most common forms of extrapulmonary tuberculosis (Tb). Patients with TPE or malignant pleural effusions (MPE) frequently have a similar lymphocytic pleural fluid profile. Since the etiology of PE in various diseases is different, identifying the cellular components may provide diagnostic clues for understanding the pathogenesis. Objective: We determined the frequency of T helper (Th) subtypes in the PEs for differentiation of Tb and non-Tb patients. Methods: Thirty patients with TPE, 30 patients with MPE, 14 patients with empyema (EMP), and 14 patients with parapneumonic effusion (PPE) were enrolled between December 2018 and December 2019. Five-milliliter fresh PE in tubes containing heparin as an anticoagulant was obtained from patients. The frequencies of CD4+IL-9+, CD4+IL-22+, CD+IL-17+, and regulatory T-cells CD4+CD25+ FOXP3+ (Treg) were determined by flow cytometry. Results: Treg cells have a lower frequency in TPE patients [4.2 (0.362-17.24)] compared with non-TPE patients [26.3 (3.349-76.93, p < 0.0001)]. The frequency of CD4+IL-9+ cells was significantly lower in TPE patients [3.67 (0.87-47.83)] compared with non-TPE groups [13.05 (1.67-61.45), p < 0.0001]. On the contrary, there was no significant difference in the frequency of CD4+IL-17+ and CD4+IL-22+ cells between TPE and non-TPE patients (p = 0.906 and p = 0.2188). Receiver-operator curve (ROC) analysis demonstrated that CD4+CD25+FOXP3+ T cells [optimal cutoff value = 13.6 (%), sensitivity 90%, specificity 75.86%] could be considered as predictor for TPE. However, adenosine deaminase [cutoff value 27.5 (IU/l), sensitivity 90%, specificity 96.5%] levels had an even greater predictive capacity. Conclusion: ADA, Treg cells, and CD4+IL-9+ cells may differentiate TPE from non-TPE patients. However, these results need validation in an independent large cohort.

4.
Eur J Investig Health Psychol Educ ; 11(4): 1440-1461, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34842659

RESUMO

The COVID-19 pandemic lockdowns were accompanied by an abrupt transition from face-to-face education to online education. The aim of this study was to evaluate the impact of the COVID-19 pandemic on academic functioning and mood in Dutch pharmacy students and PhD candidates. A total of n = 341 participants completed an online survey including questions on mood and academic functioning, assessed retrospectively for before and during the COVID-19 pandemic. Overall, during COVID-19 lockdown, significantly more time was spent on academic activities, and study grades/output significantly improved. However, the overall effects were of small magnitude, and there was great variability among students, reporting either improved, unchanged or poorer academic functioning. Compared to before COVID-19, the lockdown periods were associated with significantly increased levels of stress, anxiety, depression, fatigue, and loneliness, and a significant reduction in optimism and happiness. Significant negative correlations were found between 'performance quality' and stress, 'performance quality' and fatigue, 'study grades/output' and stress, and between 'study grades/output' and fatigue. Correlations of mood and items related to academic interactions were not statistically significant. Differential effects were seen when the data was analyzed according to sex, living situation, and ethnicity, revealing that women, students living alone, and those with a migration background reported that COVID-19 lockdowns had greater negative mood effects and a more negative impact on academic functioning. Poorer sleep quality and reduced quality of life were significantly associated with reduced mood, as well as reduced academic performance quality and role satisfaction. Regression analysis revealed that being young and not having a non-Western migration background were predictors of improved performance quality. However, only being young was a significant predictor of improved study grades/output during the COVID-19 pandemic. Increased levels of stress and fatigue were significant predictors of both reduced performance quality and poorer study grades/output during the COVID-19 pandemic. In conclusion, for the sample as a whole, the transition to online education during the COVID-19 lockdown was judged as having significant positive effects on academic performance. The lockdown periods were associated with significantly reduced mood and reduced social interactions. It should be taken into account that about one third of students reported academic functioning to be poorer during the COVID-19 pandemic. This represents a substantial group of students who require more attention and guidance to make a successful transition to online education and cope with lockdown-associated stress and fatigue.

5.
Foods ; 10(11)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34828827

RESUMO

Selenium (Se)-enriched proteins are an important dietary source of Se for humans; however, only a few Se-enriched proteins have been identified. In the present study, we tested for potential antioxidant activity by Se-enriched soy protein, both in vitro and in vivo. Se-enriched soy protein isolate (S-SPI) was shown to have a higher free radical scavenging ability compared to ordinary soy protein isolate (O-SPI). Furthermore, Caco-2 cell viability was improved by S-SPI at low doses, whereas O-SPI did not. In addition, S-SPI was shown to inhibit oxidative stress via modulation of the NRF2-HO1 signaling pathway, upregulating the expression of downstream antioxidant enzymes (GPx, SOD). To further study the antioxidant capacity of S-SPI, BALB/c female mice were given oral gavages with 0.8 mL of S-SPI or O-SPI (5 g/kg/d, 20 g/kg/d and 40 g/kg/d) or saline as control. Hepatic GPx and SOD activity increased with increasing S-SPI dosage, but not with O-SPI. Taken together, our results suggest that Se-enriched soy protein has a high antioxidant ability and may be used as a dietary supplement for people with oxidative dam-age-mediated diseases.

6.
J Clin Med ; 10(22)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34830614

RESUMO

In the Netherlands, the 2019 coronavirus (COVID-19) pandemic had a significant impact on daily life, with two extensive lockdowns enforced to combat the spread of the SARS-CoV-2 virus. These measures included the closure of bars and restaurants, and the transition from face-to-face to online education. A survey was conducted among Dutch pharmacy students and PhD-candidates to investigate the impact of COVID-19 lockdown on alcohol consumption, hangovers, and academic functioning. The analysis revealed a significant reduction in both quantity and frequency of alcohol consumption during the COVID-19 lockdown periods. This was accompanied with a significant reduction in hangover frequency and lower hangover severity during COVID-19 lockdown periods. The distribution of scores on academic performance showed great variability between respondents: while some participants reported impairment, others reported improved performance during the COVID-19 pandemic, or no change. Women reported that significantly more time investment was associated with maintaining these performance levels. Consistent among participants was the notion of reduced interactions with teachers and other students. Participants who reported more hangovers and most severe hangovers before COVID-19 benefited from the lockdown periods in terms of improved academic performance. Positive correlations were found between study grades/output and both the frequency and severity of hangovers experienced before COVID-19, suggesting that heavier drinkers, in particular, improved academic performance during the lockdown periods. In conclusion, COVID-19 lockdowns were associated with a significant reduction in both alcohol consumption and experiencing hangovers, which was, among heavier drinkers particularly, associated with significantly improved academic functioning.

7.
Nutrients ; 13(11)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34836408

RESUMO

The prevalence of asthma is increasing, but the cause remains under debate. Research currently focuses on environmental and dietary factors that may impact the gut-lung axis. Dietary fibers are considered to play a crucial role in supporting diversity and activity of the microbiome, as well as immune homeostasis in the gut and lung. This review discusses the current state of knowledge on how dietary fibers and their bacterial fermentation products may affect the pathophysiology of allergic asthma. Moreover, the impact of dietary fibers on early type 2 asthma management, as shown in both pre-clinical and clinical studies, is described. Short-chain fatty acids, fiber metabolites, modulate host immunity and might reduce the risk of allergic asthma development. Underlying mechanisms include G protein-coupled receptor activation and histone deacetylase inhibition. These results are supported by studies in mice, children and adults with allergic asthma. Fibers might also exert direct effects on the immune system via yet to be elucidated mechanisms. However, the effects of specific types of fiber, dosages, duration of treatment, and combination with probiotics, need to be explored. There is an urgent need to further valorize the potential of specific dietary fibers in prevention and treatment of allergic asthma by conducting more large-scale dietary intervention trials.

8.
Front Neurosci ; 15: 738220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744609

RESUMO

In recent years, the idea of the gut microbiota being involved in the pathogenesis of autism spectrum disorders (ASD) has attracted attention through numerous studies. Many of these studies report microbial dysregulation in the gut and feces of autistic patients and in ASD animal models. The host microbiota plays a large role in metabolism of ingested foods, and through the production of a range of metabolites it may be involved in neurodevelopmental disorders such as ASD. Two specific microbiota-derived host metabolites, p-cresol sulfate and 4-ethylphenyl sulfate, have been associated with ASD in both patients and animal models. These metabolites originate from bacterially produced p-cresol and 4-ethylphenol, respectively. p-Cresol and 4-ethylphenol are produced through aromatic amino acid fermentation by a range of commensal bacteria, most notably bacteria from the Clostridioides genus, which are among the dysregulated bacteria frequently detected in ASD patients. Once produced, these metabolites are suggested to enter the bloodstream, pass the blood-brain-barrier and affect microglial cells in the central nervous system, possibly affecting processes like neuroinflammation and microglial phagocytosis. This review describes the current knowledge of microbial dysbiosis in ASD and elaborates on the relevance and synthesis pathways of two specific ASD-associated metabolites that may form a link between the microbiota and the brain in autism. While the two discussed metabolites are promising candidates for biomarkers and (nutritional) intervention targets, more research into the role of these metabolites in ASD is required to causally connect these metabolites to ASD pathophysiology.

9.
Tissue Barriers ; : 1996830, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34719339

RESUMO

An intact intestinal barrier is crucial for immune homeostasis and its impairment activates the immune system and may result in chronic inflammation. The epithelial cells of the intestinal barrier are connected by tight junctions, which form an anastomosing network sealing adjacent epithelial cells. Tight junctions are composed of transmembrane and cytoplasmic scaffolding proteins. Transmembrane tight junction proteins at the apical-lateral membrane of the cell consist of occludin, claudins, junctional adhesion molecules, and tricellulin. Cytoplasmic scaffolding proteins, including zonula occludens, cingulin and afadin, provide a direct link between transmembrane tight junction proteins and the intracellular cytoskeleton. Each individual component of the tight junction network closely interacts with each other to form an efficient intestinal barrier. This review aims to describe the molecular structure of intestinal epithelial tight junction proteins and to characterize their organization and interaction. Moreover, clinically important biomarkers associated with impairment of gastrointestinal integrity are discussed.

10.
Pharmacol Rev ; 73(4): 198-232, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34663688

RESUMO

The incidence of noncommunicable diseases (NCDs) has increased over the last few decades, and one of the major contributors to this is lifestyle, especially diet. High intake of saturated fatty acids and low intake of dietary fiber is linked to an increase in NCDs. Conversely, a low intake of saturated fatty acids and a high intake of dietary fiber seem to have a protective effect on general health. Several mechanisms have been identified that underlie this phenomenon. In this review, we focus on pharmacological receptors, including the aryl hydrocarbon receptor, binding partners of the retinoid X receptor, G-coupled protein receptors, and toll-like receptors, which can be activated by nutritional components and their metabolites. Depending on the nutritional component and the receptors involved, both proinflammatory and anti-inflammatory effects occur, leading to an altered immune response. These insights may provide opportunities for the prevention and treatment of NCDs and their inherent (sub)chronic inflammation. SIGNIFICANCE STATEMENT: This review summarizes the reported effects of nutritional components and their metabolites on the immune system through manipulation of specific (pharmacological) receptors, including the aryl hydrocarbon receptor, binding partners of the retinoid X receptor, G-coupled protein receptors, and toll-like receptors. Nutritional components, such as vitamins, fibers, and unsaturated fatty acids are able to resolve inflammation, whereas saturated fatty acids tend to exhibit proinflammatory effects. This may aid decision makers and scientists in developing strategies to decrease the incidence of noncommunicable diseases.

11.
Sci Rep ; 11(1): 20082, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635725

RESUMO

Invariant Natural Killer T (iNKT) cells respond to the ligation of lipid antigen-CD1d complexes via their T-cell receptor and are implicated in various immunometabolic diseases. We considered that immunometabolic factors might affect iNKT cell function. To this end, we investigated iNKT cell phenotype and function in a cohort of adolescents with chronic disease and immunometabolic abnormalities. We analyzed peripheral blood iNKT cells of adolescents with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (OB, n = 20), and corrected atrial septal defect (ASD, n = 25) as controls. To study transcriptional differences, we performed RNA sequencing on a subset of obese patients and controls. Finally, we performed standardized co-culture experiments using patient plasma, to investigate the effect of plasma factors on iNKT cell function. We found comparable iNKT cell numbers across patient groups, except for reduced iNKT cell numbers in JIA patients. Upon ex-vivo activation, we observed enhanced IFN-γ/IL-4 cytokine ratios in iNKT cells of obese adolescents versus controls. The Th1-skewed iNKT cell cytokine profile of obese adolescents was not explained by a distinct transcriptional profile of the iNKT cells. Co-culture experiments with patient plasma revealed that across all patient groups, obesity-associated plasma factors including LDL-cholesterol, leptin, and fatty-acid binding protein 4 (FABP4) coincided with higher IFN-γ production, whereas high HDL-cholesterol and insulin sensitivity (QUICKI) coincided with higher IL-4 production. LDL and HDL supplementation in co-culture studies confirmed the effects of lipoproteins on iNKT cell cytokine production. These results suggest that circulating immunometabolic factors such as lipoproteins may be involved in Th1 skewing of the iNKT cell cytokine response in immunometabolic disease.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34639330

RESUMO

The aim of this study was to explore the effects of the 2019 Coronavirus (COVID-19) lockdown on mood states, stress, alcohol consumption and perceived immune fitness in a Dutch sample. Analysis included a subsample from the "Corona Lockdown: how fit are you?" (CLOFIT) study, comprising N = 761 participants who reported consuming alcohol in 2020. Results show that, compared to pre-lockdown, the first COVID-19 lockdown (March 2020) was associated with experiencing poorer mood (e.g., anxiety, depression, loneliness, fatigue) and increased stress levels. Among younger participants (18 to 35 years old), a significant decrease in weekly alcohol consumption was found during COVID-19 lockdown, which was not significant in older individuals. For the younger age cohort (18 to 35 years old), increased stress significantly correlated to increased weekly alcohol consumption (r = 0.163, p = 0.003), which in turn, correlated significantly to reporting a poorer perceived immune fitness (r = -0.165, p = 0.002). Poorer perceived immune fitness correlated significantly with increases in the presence and severity of COVID-19 symptoms (r = -0.313, p < 0.001, and r = -0.325, p < 0.001, respectively). The data provides evidence for significant relationships between changes in mood, stress and alcohol consumption during COVID-19 lockdown, and supports a model that links these changes to perceived immune fitness and susceptibility to experiencing COVID-19 symptoms.


Assuntos
COVID-19 , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Ansiedade , Controle de Doenças Transmissíveis , Humanos , SARS-CoV-2 , Adulto Jovem
13.
Front Immunol ; 12: 685742, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512624

RESUMO

Background: Pregnancy is a portentous stage in life, during which countless events are precisely orchestrated to ensure a healthy offspring. Maternal microbial communities are thought to have a profound impact on development. Although antibiotic drugs may interfere in these processes, they constitute the most frequently prescribed medication during pregnancy to prohibit detrimental consequences of infections. Gestational antibiotic intervention is linked to preeclampsia and negative effects on neonatal immunity. Even though perturbations in the immune system of the mother can affect reproductive health, the impact of microbial manipulation on maternal immunity is still unknown. Aim: To assess whether antibiotic treatment influences maternal immunity during pregnancy. Methods: Pregnant mice were treated with broad-spectrum antibiotics. The maternal gut microbiome was assessed. Numerous immune parameters throughout the maternal body, including placenta and amniotic fluid were investigated and a novel machine-learning ensemble strategy was used to identify immunological parameters that allow distinction between the control and antibiotic-treated group. Results: Antibiotic treatment reduced diversity of maternal microbiota, but litter sizes remained unaffected. Effects of antibiotic treatment on immunity reached as far as the placenta. Four immunological features were identified by recursive feature selection to contribute to the most robust classification (splenic T helper 17 cells and CD5+ B cells, CD4+ T cells in mesenteric lymph nodes and RORγT mRNA expression in placenta). Conclusion: In the present study, antibiotic treatment was able to affect the carefully coordinated immunity during pregnancy. These findings highlight the importance of inclusion of immunological parameters when studying the effects of medication used during gestation.


Assuntos
Imunidade Adaptativa/imunologia , Animais Recém-Nascidos/imunologia , Anticorpos Antibacterianos/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Microbioma Gastrointestinal/imunologia , Animais , Animais Recém-Nascidos/microbiologia , Antibacterianos/farmacologia , Feminino , Microbioma Gastrointestinal/genética , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Intestinos/microbiologia , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Gravidez
14.
J Clin Med ; 10(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34575350

RESUMO

Assessment of the presence and severity of alcohol hangovers relies on the subjective method of self-report. Therefore, there is a need of adequate biomarkers that (1) correlate significantly with hangover severity, and (2) correspond to the level of hangover-related performance impairment objectively. In this naturalistic study, n = 35 social drinkers participated. Urine samples were obtained the morning after alcohol consumption and after an alcohol-free control day. Concentrations of 5-hydroxytryptophol (5-HTOL), 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HTOL/5-HIAA ratio were determined. The results confirm previous findings that 5-HTOL and the 5HTOL/5-HIAA ratio are useful biomarkers of recent alcohol consumption. Significant correlations were found with the amount of alcohol consumed, total drink time, and estimated BAC. However, urine concentrations of 5-HTOL and 5-HIAA (and their ratio 5HTOL/5-HIAA) did not significantly correlate with hangover severity. In conclusion, urine 5-HTOL, 5-HIAA, and the 5HTOL/5-HIAA ratio cannot be considered to be suitable biomarkers of alcohol hangover.

15.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576216

RESUMO

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders characterised by behavioural impairment and deficiencies in social interaction and communication. A recent study estimated that 1 in 89 children have developed some form of ASD in European countries. Moreover, there is no specific treatment and since ASD is not a single clinical entity, the identification of molecular biomarkers for diagnosis remains challenging. Besides behavioural deficiencies, individuals with ASD often develop comorbid medical conditions including intestinal problems, which may reflect aberrations in the bidirectional communication between the brain and the gut. The impact of faecal microbial composition in brain development and behavioural functions has been repeatedly linked to ASD, as well as changes in the metabolic profile of individuals affected by ASD. Since metabolism is one of the major drivers of microbiome-host interactions, this review aims to report emerging literature showing shifts in gut microbiota metabolic function in ASD. Additionally, we discuss how these changes may be involved in and/or perpetuate ASD pathology. These valuable insights can help us to better comprehend ASD pathogenesis and may provide relevant biomarkers for improving diagnosis and identifying new therapeutic targets.


Assuntos
Transtorno do Espectro Autista/microbiologia , Transtorno do Espectro Autista/fisiopatologia , Microbioma Gastrointestinal , Comportamento , Biomarcadores/metabolismo , Barreira Hematoencefálica , Encéfalo/fisiologia , Criança , Pré-Escolar , Fezes , Feminino , Humanos , Masculino , Metaboloma , Neurotransmissores/metabolismo , Polissacarídeos/química
16.
Nutrients ; 13(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34578853

RESUMO

Human milk serves as a model for infant formula providing nutritional solutions for infants not able to receive enough mother's milk. Infant formulas aim to mimic the composition and functionality of human milk by providing ingredients reflecting those of the latest human milk insights, such as prebiotics, probiotics and postbiotics. The aim of this study was to examine the effects of the supplementation with a postbiotic (LactofidusTM) and its combination with the prebiotics short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) in a preclinical model of healthy suckling rats. Pups were supplemented daily with LactofidusTM (POST group) and/or scGOS/lcFOS (P+P and PRE groups, respectively). Body weight and fecal consistency were analyzed. At the end of the study, immunoglobulin (Ig) profile, intestinal gene expression, microbiota composition and short chain fatty acid (SCFA) proportion were quantified. The supplementation with all nutritional interventions modulated the Ig profile, but the prebiotic mixture and the postbiotic induced differential effects: whereas scGOS/lcFOS induced softer feces and modulated microbiota composition and SCFA profile, Lactofidus™ upregulated Toll-like receptors gene expression. The use of the combination of scGOS/lcFOS and Lactofidus™ showed the effects observed for the oligosaccharides separately, as well as showing a synergistic impact on animal growth. Thus, the combined use of both products seems to be a good strategy to modulate immune and microbial features in early life.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Imunidade/efeitos dos fármacos , Imunidade/imunologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Animais , Animais Recém-Nascidos , Modelos Animais , Prebióticos/microbiologia , Ratos
17.
Nutrients ; 13(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34579070

RESUMO

Deoxynivalenol (DON), a highly prevalent mycotoxin food contaminant, is known to have immunotoxic effects. In the current study, the potential of dietary interventions with specific mixtures of trans-galactosyl-oligosaccharides (TOS) to alleviate these effects were assessed in a murine influenza vaccination model. Vaccine-specific immune responses were measured in C57Bl/6JOlaHsd mice fed diets containing DON, TOS or a combination, starting 2 weeks before the first vaccination. The direct effects of TOS and its main oligosaccharide, 3'-galactosyl-lactose (3'-GL), on DON-induced damage were studied in Caco-2 cells, as an in vitro model of the intestinal epithelial barrier. Exposure to DON significantly reduced vaccine-specific immune responses and the percentages of Tbet+ Th1 cells and B cells in the spleen. DON significantly altered epithelial structure and integrity in the ileum and reduced the SCFA levels in the cecum. Adding TOS into DON-containing diets significantly improved vaccine-specific immune responses, restored the immune cell balance in the spleen and increased SCFA concentrations in the cecum. Incubating Caco-2 cells with TOS and 3'-GL in vitro further confirmed their protective effects against DON-induced barrier disruption, supporting immune modulation. Overall, dietary intervention with TOS can attenuate the adverse effects of DON on Th1-mediated immune responses and gut homeostasis. These beneficial properties might be linked to the high levels of 3'-GL in TOS.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Influenza Humana/imunologia , Leite Humano/química , Oligossacarídeos/farmacologia , Tricotecenos/imunologia , Trissacarídeos/farmacologia , Vacinação , Animais , Células CACO-2 , Ceco/efeitos dos fármacos , Dieta , Ácidos Graxos Voláteis/metabolismo , Feminino , Contaminação de Alimentos , Humanos , Intestinos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Micotoxinas/imunologia , Baço/efeitos dos fármacos , Células Th1/metabolismo , Vacinas/imunologia
18.
Cells ; 10(9)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34571936

RESUMO

Multiple myeloma (MM) is a hematological malignancy that exhibits aberrantly high levels of proteasome activity. While treatment with the proteasome inhibitor bortezomib substantially increases overall survival of MM patients, acquired drug resistance remains the main challenge for MM treatment. Using a combination treatment of docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) and bortezomib, it was demonstrated previously that pretreatment with DHA/EPA significantly increased bortezomib chemosensitivity in MM cells. In the current study, both transcriptome and metabolome analysis were performed to comprehensively evaluate the underlying mechanism. It was demonstrated that pretreating MM cells with DHA/EPA before bortezomib potently decreased the cellular glutathione (GSH) level and altered the expression of the related metabolites and key enzymes in GSH metabolism, whereas simultaneous treatment only showed minor effects on these factors, thereby suggesting the critical role of GSH degradation in overcoming bortezomib resistance in MM cells. Moreover, RNA-seq results revealed that the nuclear factor erythroid 2-related factor 2 (NRF2)-activating transcription factor 3/4 (ATF3/4)-ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1) signaling pathway may be implicated as the central player in the GSH degradation. Pathways of necroptosis, ferroptosis, p53, NRF2, ATF4, WNT, MAPK, NF-κB, EGFR, and ERK may be connected to the tumor suppressive effect caused by pretreatment of DHA/EPA prior to bortezomib. Collectively, this work implicates GSH degradation as a potential therapeutic target in MM and provides novel mechanistic insights into its significant role in combating bortezomib resistance.


Assuntos
Biomarcadores Tumorais/metabolismo , Bortezomib/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Humanos , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Transdução de Sinais , Células Tumorais Cultivadas
19.
Eur J Investig Health Psychol Educ ; 11(1): 183-198, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542458

RESUMO

Collecting real-world evidence via 'at home' assessments in ambulatory patients or healthy volunteers is becoming increasingly important, both for research purposes and in clinical practice. However, given the mobile technology that is frequently used for these assessments, concise assessments are preferred. The current study compared single-item ratings with multiple-item subscale scores of the same construct, by calculating the corresponding Bland and Altman 95% limits of agreement interval. The analysis showed that single-item ratings are usually in good agreement with assessments of their corresponding subscale. In the case of more complex multimodal constructs, single-item assessments were much less often in agreement with multiple-item questionnaire outcomes. The use of single-item assessments is advocated as they more often incorporate assessments of all aspects of a certain construct (including the presence, severity, and impact of the construct under investigation) compared to composite symptom scores.

20.
Eur J Investig Health Psychol Educ ; 11(1): 199-218, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542459

RESUMO

This article provides an overview of the design and methodology of the "Corona lockdown: how fit are you?" (CLOFIT) study, including the questionnaires and scales that were included in the online survey. The aim of the CLOFIT study was to investigate the psychosocial and health consequences of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands. The survey was conducted among the Dutch population to collect data on immune fitness and the psychological and health consequences of the 2019 coronavirus disease (COVID-19) pandemic lockdown in the Netherlands. The CLOFIT dataset contains measures from N = 1910 participants and is broadly representative of the Dutch general population. The dataset represents both sexes, a range of ages including the elderly, different education levels, and ethnic backgrounds. The cohort also includes people with a diverse health status and range of medication use.

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