Exosomes are extracellular vesicles (EVs) that regulate intercellular signaling by transferring small RNAs, proteins, nucleic acids, lipids, and other metabolites to local or distant organs, ...including the brain, by crossing the blood–brain barrier. However, the transport of (poly)phenols in human EVs has not yet been described. Therefore, we aimed here to explore (i) whether resveratrol and (or) its derived metabolites are found in the cargo of human plasma exosome-containing EVs (E-EVs), (ii) when this incorporation occurs, and (iii) whether resveratrol intake stimulates the release of E-EVs. Thus, in a pharmacokinetic study, healthy volunteers (n = 16) consumed 1 capsule (420 mg resveratrol) in the evening before attending the clinic and one more capsule on the day of the pharmacokinetics. The plasma and the isolated E-EVs were analyzed using UPLC-ESI-QTOF-MS. Of 17 metabolites in the plasma, 9 were identified in the E-EVs, but not free resveratrol. The kinetic profiles of resveratrol metabolites were similar in the plasma and the E-EVs, a higher metabolite concentration being detected in the plasma than in the E-EVs. However, the plasma/E-EVs ratio decreased in the gut microbial metabolites, suggesting their better encapsulation efficiency in E-EVs. In addition, glucuronide conjugates of resveratrol, dihydroresveratrol, and lunularin were incorporated into the E-EVs more efficiently than their corresponding sulfates despite glucuronides reaching lower plasma concentrations. Notably, more E-EVs were detected 10 h after resveratrol consumption. This exploratory study provides the first evidence that (i) resveratrol metabolites are transported by E-EVs, with a preference for glucuronide vs. sulfates, (ii) the gut microbial metabolites concentration and kinetic profiles are closely similar in E-EVs and plasma, and (iii) resveratrol intake elicits E-EVs secretion. Overall, these results open new research avenues on the possible role of E-EVs in (poly)phenol health effects.
Objectives: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes. Methods: Four hundred and ...ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed. Results: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development. Conclusion: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS.
The purpose of this study is to redesign a web portal, oriented to communication and employment management for older adults, from the perspective of user experience, using the user experience ...methodology. The graphic and functional elements of the platform were considered, enhancing the effectiveness of the communication and inclusion processes and accessibility to employment opportunities. The study is part of a mixed investigation, attending the following stages: (a) exploration of the users of the ServiSenior portal platform during 2021 (constituted by 11 collaborators, 15 clients, and 30 older adults); (b) documentary analysis of the state of the art of employment portals for older adults; (c) proposal design incorporating user experience improvements; (d) testing to validate the value proposition delivered to the target audience. The results obtained were taken into account in decision-making for the approach to the design of the digital portal. This proposal is theoretically based on user-centered design, from which the user experience methodology emerges, which seeks to improve the use and quality of services of digital portals centered on users, emphasizing the attribute of universal use and access. The results obtained enhance the applicability of digital tools that serve to insert a vulnerable population in work spaces, assuming as a starting point design, accessibility, and ease of use.
To clinicopathologically characterize the diagnosis of oral lichenoid disease (OLD) and its main subtypes: oral lichen planus (OLP) and oral lichenoid lesion (OLL), in order to correctly asses their ...prognosis.
Ambispective cohort study of 384 patients with diagnosis of OLD, based on pre-established clinical and histopathological criteria. We have analysed 272 (70.8%) women and 112 (29.2%), whose mean age was 57.1+/-11.8 years (range 21-90); minimum follow-up time was 36 months. A specific protocol was designed for this study, where we gathered the data of each patient, including malignant transformation.
OLP was diagnosed in 229 cases (77.9%) and OLL in 85 (22.1%). Tobacco consumption was found in 20.3% of the patients and alcohol intake in 41.1%. Liver pathology was present in 10.7% of the cases, thyroid pathology in 11.5%, arterial hypertension in 15.6%, diabetes mellitus in 7.6%, psycho-emotional disorders in 33.3%, skin involvement in 12% and genital involvement in 4.9%. Ten patients (2.6%) developed an oral squamous cell carcinoma, 5 (1.7%) with OLP and 5 (5.9%) with OLL.
OLD is a potentially malignant disorder of the oral mucosa which has to be correctly diagnosed as either OLP or OLL, since the risk of malignancy of these subtypes is significantly different.
Structural and functional neuroimaging studies have shown that brain areas associated with fear and anxiety (defensive system areas) are modulated by individual differences in sensitivity to ...punishment (SP). However, little is known about how SP is related to brain functional connectivity and the factors that modulate this relationship. In this study, we investigated whether a simple methodological manipulation, such as performing a resting state with eyes open or eyes closed, can modulate the manifestation of individual differences in SP. To this end, we performed an exploratory fMRI resting state study in which a group of participants (n = 88) performed a resting state with eyes closed and another group (n = 56) performed a resting state with eyes open. All participants completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Seed-based functional connectivity analyses were performed in the amygdala, hippocampus, and periaqueductal gray (PAG). Our results showed that the relationship between SP and left amygdala-precuneus and left hippocampus-precuneus functional connectivity was modulated by eye state. Moreover, in the eyes open group, SP was negatively related to the functional connectivity between the PAG and amygdala and between the PAG and left hippocampus, and it was positively related to the functional connectivity between the amygdala and hippocampus. Together, our results may suggest underlying differences in the connectivity between anxiety-related areas based on eye state, which in turn would affect the manifestation of individual differences in SP.
Abstract Objective Fetal and postnatal zinc deficiencies induce an increase in arterial blood pressure and impair renal function in male adult rats. We therefore hypothesized that these renal ...alterations are present in early stages of life and that there are sexual differences in the adaptations to this nutritional injury. The aim was to study the effects of moderate zinc deficiency during fetal life and lactation on renal morphology, oxidative stress, apoptosis, and the nitric oxide system in male and female rats at 21 d of life. Methods Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy to weaning. Glomerulus number, morphology, oxidative stress, apoptotic cells, nitric oxide synthase activity, and protein expression were evaluated in the kidneys of offspring at 21 d. Results Zinc deficiency decreased the nephron number, induced glomerular hypertrophy, increased oxidative damage, and decreased nitric oxide synthase activity in the male and female rat kidneys. Nitric oxide synthase activity was not affected by inhibitors of the neuronal or inducible isoforms, so nitric oxide was mainly generated by the endothelial isoenzyme. Gender differences were observed in glomerular areas and antioxidant enzyme activities. Conclusion Zinc deficiency during fetal life and lactation induces an early decrease in renal functional units, associated with a decrease in nitric oxide activity and an increase in oxidative stress, which would contribute to increased arterial blood pressure and renal dysfunction in adulthood. The sexual differences observed in this model may explain the dissimilar development of hypertension and renal diseases in adult life.
Caries and chronic periodontitis are common oral diseases where a higher
Candida
colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The ...aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral
Candida
isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral
Candida
isolates (75
Candida albicans,
18
Candida parapsilosis
, 11
Candida dubliniensis
, six
Candida guilliermondii,
five
Candida lipolytica
, five
Candida glabrata
, four
Candida tropicalis
and two
Candida krusei
) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all
Candida
isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.
Se ha comprobado que la innovación es fundamental para la supervivencia de las empresas al igual que para el crecimiento de un país, por tal motivo una eficiente inversión en innovación permitirá ...obtener resultados óptimos y a su vez conseguir mejoras en la organización de la empresa, eficiencia en la gestión y sobre todo obtener ventajas competitivas que generen una consolidación en el mercado. En el presente estudio se examina cómo determinantes de la innovación, en específico: La innovación de productos, la innovación de procesos y las patentes, influyen en el resultado de la innovación en empresas manufactureras españolas; considerando el efecto que ejercen los outputs de innovación a partir de los inputs de innovación (gastos internos de I+D, gastos externos de I+D, financiación pública, personal especializado en I+D y cooperación con agentes externos) durante el período 2003-2016. Este análisis empírico utiliza una muestra de 12.849 empresas que ejecutan actividad innovadora en territorio español, por medio de la base de datos PITEC. Los principales resultados obtenidos reflejan que todos los indicadores analizados favorecen el proceso innovador de las empresas, admitiendo como conclusión, una relación causal entre los esfuerzos aplicados en innovación y la capacidad de respuesta de las empresas.
The aim of the study was to analyze the histopathological characteristics of samples with a diagnosis of oral lichenoid disease (OLD) and their link with the location and the type of clinical lesion, ...and the clinicopathological subtypes.
Retrospective study on 85 consecutive patients diagnosed with OLD (58 women and 27 men, mean age of 57.7 years). Clinical and histopathological characterization of each case (modified WHO criteria). Collection of the clinical and histopathological data of the lesions. Descriptive and comparative statistical analysis of the results.
The 78.8% of the cases were considered clinically typical while the 21.2% were considered compatible. Histologically, 52.9% were classified as typical and 47.1% as compatible. Biopsies from "plaque-like" lesions presented hyperkeratosis (p>0.001) and epithelial dysplasia (p=0.06) more frequently. Furthermore, acute inflammation was more evident in erosive-ulcerative lesions (p=0.001). Differences regarding the location of the biopsy were statistically non-significant. However, 42.9% of the tongue biopsies showed epithelial dysplasia.
The histopathological aspect of this disorder is not specific and does not allow us to differentiate between the main subtypes. Therefore, the main reasons to perform a biopsy in this disorder are to define the differential diagnosis and to rule out epithelial dysplasia or a carcinoma. The final histopathological result may be subject to the type of lesion that is biopsied.
We aimed to identify the plasma miRNA profile of antiphospholipid syndrome (APS) patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease biomarkers. ...Ninety APS patients and 42 healthy donors were recruited. Profiling of miRNAs by PCR-array in plasma of APS patients identified a set of miRNAs differentially expressed and collectively involved in clinical features. Logistic regression and ROC analysis identified a signature of 10 miRNA ratios as biomarkers of disease. In addition, miRNA signature was related to fetal loss, atherosclerosis, and type of thrombosis, and correlated with parameters linked to inflammation, thrombosis, and autoimmunity. Hard clustering analysis differentiated 3 clusters representing different thrombotic risk profile groups. Significant differences between groups for several miRNA ratios were found. Moreover, miRNA signature remained stable over time, demonstrated by their analysis three months after the first sample collection. Parallel analysis in two additional cohorts of patients, including thrombosis without autoimmune disease, and systemic lupus erythematosus without antiphospholipid antibodies, each displayed specific miRNA profiles that were distinct from those of APS patients.
, antiphospholipid antibodies of IgG isotype promoted deregulation in selected miRNAs and their potential atherothrombotic protein targets in monocytes and endothelial cells. Taken together, differentially expressed circulating miRNAs in APS patients, modulated at least partially by antiphospholipid antibodies of IgG isotype, might have the potential to serve as novel biomarkers of disease features and to typify patients' atherothrombotic status, thus constituting a useful tool in the management of the disease.
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