El sinoviocito fibroblástico en la artrosis. Efecto protector de VIP y CRF

La artrosis (OA) es una enfermedad reumática crónica degenerativa y multifactorial. Es la artropatía más frecuente y la principal causa de daño y disfunción entre la población de mediana edad y anciana, caracterizada por una pérdida progresiva de la función de las articulaciones sinoviales (Bondeson et al., 2010; Loeser et al., 2012). Aunque la artritis reumatoide (AR) es la enfermedad reumática autoinmune inflamatoria por excelencia, más del 50% de los pacientes artrósicos también poseen signos de inflamación (Monfort, 2010; Pelletier et al., 2001; Scanzello y Goldring, 2012). Durante la sinovitis, el sinoviocito fibroblástico (SF) juega un papel esencial mediante la liberación de mediadores inflamatorios (Benito et al., 2005; Bottini y Firestein, 2013), entre los que se incluyen citocinas como la IL‐1β (Goldring et al., 2011; Stylianou y Saklatvala, 1998). Por otro lado, durante el proceso de destrucción articular se liberan componentes de la matriz extracelular (MEC) con propiedades potencialmente inflamatorios, incluyendo a la fibronectina y sus fragmentos de degradación (Fn‐fs) (Homandberg et al., 1998; Zack et al., 2006). Estos mediadores contribuyen a la destrucción del cartílago articular, rompiendo el balance entre degradación y síntesis de la MEC, como consecuencia de una expresión alterada de las proteinasas (Attur et al., 2002; Kato et al., 2014; Pelletier et al., 2001; Troeberg y Nagase, 2012)..

VIP and CRF reduce ADAMTS expression and function in osteoarthritis synovial fibroblasts

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family is known to play an important role in the pathogenesis of osteoarthritis (OA), working on aggrecan degradation or altering the integrity of extracellular matrix (ECM). Thus, the main purpose of our study was to define the role of vasoactive intestinal peptide (VIP) and corticotrophin-releasing factor (CRF), as immunoregulatory neuropeptides, on ADAMTS production in synovial fibroblasts (SF) from OA patients and healthy donors (HD). OA- and HD-SF were stimulated with pro-inflammatory mediators and treated with VIP or CRF. Both neuropeptides decreased ADAMTS-4, -5, -7 and -12 expressions, aggrecanase activity,glycosaminoglycans (GAG), and cartilage oligomeric matrix protein (COMP) degradation after stimulation with fibronectin fragments (Fn-fs) in OA-SF. After stimulation with interleukin-1b, VIP reduced ADAMTS-4 and -5, and both neuropeptides decreased ADAMTS-7 production and COMP degradation. Moreover, VIP and CRF reduced Runx2 and b-catenin activation in OA-SF. Our data suggest that the role of VIP and CRF on ADAMTS expression and cartilage degradation could be related to the OA pathology since scarce effects were produced in HD-SF. In addition,their effects might be greater when a degradation loop has been established, given that they were higher after stimulation with Fn-fs. Our results point to novel OA therapies based on the use of neuropeptides, since VIP and CRF are able to stop the first critical step, the loss of cartilageaggrecan and the ECM destabilization during joint degradatio

Examining the Relation Between Practicing Meditation and Having Peak Experiences and Lucid Dreams. A Cross-Sectional Study

The aim of this study was to compare meditators and non-meditators in terms of their tendency to have peak experiences and their dream lucidity, while examining the associations between these outcomes and some related variables such as non-dual awareness, mindfulness facets and absorption. In this cross-sectional study, 237 participants from general Spanish population completed an online survey that included ad hoc questions related to the study aim, along with the Five Facet Mindfulness Questionnaire (FFMQ), the Non-dual Embodiment Thematic Inventory (NETI), the Tellegen Absorption Scale (TAS) and the Lucidity and Consciousness in Dreams Scale (LUCID). Of the total, 110 participants were identified as meditators and 127 as non-meditators. More than half of the sample (58.2%) reported having experienced at least one peak experience in their life; these showed no differences in the number, intensity, or self-inducing ability of these experiences between both groups but were significantly more common among meditators (71.8% vs. 46.8%; p < 0.001), who also presented higher scores in most of the questionnaires, except for some LUCID subscales. Regression models demonstrated that being a meditator was a significant predictor of having had a peak experience, but not of LUCID scores. These results, which need to be interpreted considering the study limitations, support the potential of meditation to facilitate having peak experiences, while its impact on lucid dreams remains unclear

Macaúba’s world scenario: a bibliometric analysis

Macaúba is a tropical palm native in South and Central America, and its fruits present a high-quality oil for biodiesel production. Notwithstanding, macaúba's wastes and by-products are not usually repurposed as energy sources. This study shows a bibliometric analysis to assess macaúba's current applications and to investigate other energy recovery routes for its by-products. All the investigations focused on information about the main research fields related to macaúba. The study showed that only 397 articles and reviews were published from 1900 until 2021, and Brazil is the leading publisher. Although oleic and protein macaúba's by-products are applied as animal feed, some conversion routes related to the lignocellulosic contents, present in non-edible parts, were identified thermal conversion, combustion, gasification, pyrolysis, biochemical conversion, fermentation, esterification, and anaerobic digestion. From the agricultural perspective, plant characterization, germination, embryogenesis, and seed development were also found. From the bibliometric study, the different potential applications of macaúba for energy, pharmaceutical, and food purposes were listed to support the identification of a knowledge gap on its by-products revaluation

Green Extraction Processes for Complex Samples from Vegetable Matrices Coupled with On-Line Detection System: A Critical Review

The detection of analytes in complex organic matrices requires a series of analytical steps to obtain a reliable analysis. Sample preparation can be the most time-consuming, prolonged, and error-prone step, reducing the reliability of the investigation. This review aims to discuss the advantages and limitations of extracting bioactive compounds, sample preparation techniques, automation, and coupling with on-line detection. This review also evaluates all publications on this topic through a longitudinal bibliometric analysis, applying statistical and mathematical methods to analyze the trends, perspectives, and hot topics of this research area. Furthermore, state-of-the-art green extraction techniques for complex samples from vegetable matrices coupled with analysis systems are presented. Among the extraction techniques for liquid samples, solid-phase extraction was the most common for combined systems in the scientific literature. In contrast, for on-line extraction systems applied for solid samples, supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, and pressurized liquid extraction were the most frequent green extraction techniques

Vasoactive Intestinal Peptide maintains the non-pathogenic profile of human Th17-polarized cells

The cytokine microenvironment modulates CD4 T cell differentiation causing the shift of naïve CD4 T cells into different cell subsets. This process is also regulated by modulators such as VIP, a neuropeptide with known immunomodulatory properties on CD4 T cells that exert this action through specific receptors, VPAC1 and VPAC2. Our results show that the pattern of VIP receptors expression ratio is modified during Th17 differentiation. In this report, we evaluate the capacity of VIP to modulate naïve human cells into Th17 cells in vitro by analyzing their functional phenotype. The presence of VIP maintains the non-pathogenic profile of Th17-polarized cells, increases the proliferation rate and decreases their Th1 potential. VIP induces the up-regulation of the STAT3 gene interaction with the VPAC1 receptor during the onset of Th17 differentiation. Moreover, RORC, RORA and IL-17A genes are up-regulated in the presence of VIP through interaction with VPAC1 and VPAC2 receptors. Interestingly, VIP induces the expression of the IL-23R gene through interaction with the VPAC2 receptor during the expansion phase. This is the first report that describes the differentiation of naïve human T cells to Th17-polarized cells in the presence of VIP and demonstrates how this differentiation regulates the expression of the VIP receptors

Techno-economic evaluation of bioenergy production from anaerobic digestion of by-products from ethanol flex plants

Ethanol production implies in by-products generation, mainly vinasse and stillage, respectively generated from sugarcane and corn ethanol production in flex plants. Both by-products require efficient treatment routes to avoid environmental side-effects to support energy recovery. Accordingly, the aim of this study was to evaluate the techno-economic potential of bioenergy (electric and thermal energy) production from the anaerobic digestion (AD) of vinasse and stillage. Three scenarios were defined: (a) Scenario 1, AD of vinasse; (b) Scenario 2, AD of stillage; and (c) Scenario 3, AD of vinasse and stillage in an integrated process. From the results, the methane production was estimated at 3.8 x 106 m3 year-1 considering the AD of stillage and vinasse in Scenario 3. The electricity and thermal energy generation was estimated as 14.61 GWh year-1 and 1.37 x 105 GJ year-1, respectively. This energy would mitigate 1096.05 and 7659.27 ton CO2eq year-1 when replacing fossil fuel energy. The profitability analysis indicated a positive net present value in the scenarios evaluated, however, the highest value was achieved for Scenario 3 (7,890,407.44 USD). For the integrated process, an internal return rate of 86.87% and a payback of 0.68 year were observed. The sensitivity analysis showed that the project profitability is highly dependent on electricity and thermal energy selling prices. In conclusion, AD demonstrated to be a feasible alternative for vinasse and stillage management in an integrated process, being a sustainable technology to the circular economy transition and energy matrix decarbonization.T. Forster-Carneiro acknowledges the database support and samples of materials from NIPE/NIEPE-UNICAMP/UFMT, process numbers 91.752/01-P-17839-2019 and 91759/01-P-18069/2019. T. Forster-Carneiro acknowledges the financial support from the Sao Paulo Research Foundation - FAPESP (2018/05999-0; 2018/14938-4) , and CNPq for the productivity grant (302473/2019-0) . L.S. Buller ac-knowledges the financial support from FAPESP (2020/10323-5) . W.G. Sganzerla acknowledges the financial support from FAPESP (2019/26925-7) . M. Tena acknowledges the Spanish Ministry of Economy, Industry, and Competitiveness for her pre-doctoral contract (Call 2016)

Estudio teórico de la ruta de degradación del sulfametoxazol vía radicales hidroxilo utilizando la Teoría de Funcionales de la Densidad

Artículo número 57 de la Sección 3. Química de Materiales. Química TeóricaSe estudió una de las posibles rutas de degradación del sulfametoxazol mediante radicales hidroxilo •OH utilizando la teoría de funcionales de la densidad (DFT, por sus siglas en inglés), con el propósito evaluar su factibilidad termodinámica y esclarecer los subproductos asociados a sus reacciones. Los resultados condujeron a la confirmación de un compuesto especulado y a la identificación de dióxido de azufre como posible subproducto. También, se realizó un análisis estructural y de sitios reactivos para la molécula del sulfametoxazol, comparando los resultados obtenidos teóricamente con datos experimentales; mostrando la utilidad de la DFT para representar sistemas químicos, así como para explicar y discernir entre diferentes mecanismos de reacción.One possible route of degradation of sulfamethoxazole by hydroxyl •OH radicals were explored through density functional theory (DFT), with the purpose of finding its thermodynamic feasibility and clarifying the by-products associated with its reactions. The results led to the confirmation of a speculated compound and the identification of sulfur dioxide as a possible by-product. Also, the structure and reactive sites of the sulfamethoxazole molecule were analyzed, comparing the results obtained theoretically with experimental data; showing the usefulness of the DFT to represent chemical systems, as well as to explain and discern between different reaction mechanisms

An Overview of VPAC Receptors in Rheumatoid Arthritis: Biological Role and Clinical Significance

The axis comprised by the Vasoactive Intestinal Peptide (VIP) and its G protein-coupled receptors (GPCRs), VPAC1, and VPAC2, belong to the B1 family and signal through Gs or Gq proteins. VPAC receptors seem to preferentially interact with Gs in inflammatory cells, rather than Gq, thereby stimulating adenylate cyclase activity. cAMP is able to trigger various downstream pathways, mainly the canonical PKA pathway and the non-canonical cAMP-activated guanine nucleotide exchange factor (EPAC) pathway. Classically, the presence of VPACs has been confined to the plasma membrane; however, VPAC1 location has been described in the nuclear membrane in several cell types such as activated Th cells, where they are also functional. VPAC receptor signaling modulates a number of biological processes by tipping the balance of inflammatory mediators in macrophages and other innate immune cells, modifying the expression of TLRs, and inhibiting MMPs and the expression of adhesion molecules. Receptor signaling also downregulates coagulation factors and acute-phase proteins, promotes Th2 over Th1, stimulates Treg abundance, and finally inhibits a pathogenic Th17 profile. Thus, the VIP axis signaling regulates both the innate and adaptive immune responses in several inflammatory/autoimmune diseases. Rheumatoid arthritis (RA) is a complex autoimmune disease that develops on a substrate of genetically susceptible individuals and under the influence of environmental factors, as well as epigenetic mechanisms. It is a heterogeneous disease with different pathogenic mechanisms and variable clinical forms between patients with the same diagnosis. The knowledge of VIP signaling generated in both animal models and human ex vivo studies can potentially be translated to clinical reality. Most recently, the beneficial effects of nanoparticles of VIP self-associated with sterically stabilized micelles have been reported in a murine model of RA. Another novel research area is beginning to define the receptors as biomarkers in RA, with their expression levels shown to be associated with the activity of the disease and patients-reported impairment. Therefore, VPAC expression together VIP genetic variants could allow patients to be stratified at the beginning of the disease with the purpose of guiding personalized treatment decisions

RELACIÓN ENTRE NIVELES DE COMPRENSIÓN LECTORA Y NIVELES DE DESEMPEÑO DEL DOMINIO COGNITIVO DE ORTOGRAFÍA

El presente trabajo de investigación tiene como propósito identificar los niveles de lacomprensión lectora, desempeño del dominio cognitivo de la ortografía y la relación queexiste entre ambos.El estudio se realizó con una población muestral de 54 niños de segundo grado del nivelprimario, se realizo una prueba de comprensión lectora evaluando los 3 niveles: nivel literal,nivel inferencial y nivel crítico. Así mismo, se realizó la prueba de desempeño del dominiocognitivo de la ortografía evaluando los 3 niveles: nivel básico, nivel reflexivo y nivelcreativo, aplicando el diseño de investigación descriptivo correlacional. Existe una relación entre los niveles de la comprensión lectora y desempeño del dominiocognitivo de la ortografía.