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1.
Nature ; 583(7817): 585-589, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669716

RESUMO

Bone marrow transplantation therapy relies on the life-long regenerative capacity of haematopoietic stem cells (HSCs)1,2. HSCs present a complex variety of regenerative behaviours at the clonal level, but the mechanisms underlying this diversity are still undetermined3-11. Recent advances in single-cell RNA sequencing have revealed transcriptional differences among HSCs, providing a possible explanation for their functional heterogeneity12-17. However, the destructive nature of sequencing assays prevents simultaneous observation of stem cell state and function. To solve this challenge, we implemented expressible lentiviral barcoding, which enabled simultaneous analysis of lineages and transcriptomes from single adult HSCs and their clonal trajectories during long-term bone marrow reconstitution. Analysis of differential gene expression between clones with distinct behaviour revealed an intrinsic molecular signature that characterizes functional long-term repopulating HSCs. Probing this signature through in vivo CRISPR screening, we found the transcription factor TCF15 to be required and sufficient to drive HSC quiescence and long-term self-renewal. In situ, Tcf15 expression labels the most primitive subset of true multipotent HSCs. In conclusion, our work elucidates clone-intrinsic molecular programmes associated with functional stem cell heterogeneity and identifies a mechanism for the maintenance of the self-renewing HSC state.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem da Célula , Hematopoese , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Análise de Célula Única , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Sistemas CRISPR-Cas , Autorrenovação Celular , Feminino , Camundongos
2.
Microb Pathog ; 190: 106610, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38484920

RESUMO

Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells.


Assuntos
Antígenos CD , Molécula CD68 , Imunofenotipagem , Hanseníase Virchowiana , Macrófagos , Humanos , Macrófagos/imunologia , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/patologia , Masculino , Feminino , Citocinas/metabolismo , Antígenos de Diferenciação Mielomonocítica , Lobomicose/imunologia , Lobomicose/patologia , Pessoa de Meia-Idade , Adulto , Pele/patologia , Pele/imunologia , Idoso , Óxido Nítrico Sintase Tipo II/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/imunologia
3.
Biochem Genet ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38814383

RESUMO

The host immune response might confer differential vulnerability to SARS-CoV-2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID-19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory-confirmed COVID-19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID-19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05-2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.

4.
J Adv Nurs ; 80(1): 350-365, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37452500

RESUMO

AIMS: To (i) assess the adherence of long-term care (LTC) facilities to the COVID-19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. DESIGN: Cross-sectional survey. METHODS: Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID-19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. RESULTS: The adherence was significantly higher among facilities with more pre-pandemic in-service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work-life imbalance. CONCLUSIONS: Pre-pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. IMPACT: This is the first study to comprehensively examine the adherence of LTC facilities to COVID-19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre-pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Assistência de Longa Duração , Estudos Transversais , Pandemias/prevenção & controle , Hong Kong/epidemiologia
5.
Entropy (Basel) ; 26(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38392379

RESUMO

There is a general agreement among researchers that supercritical carbon dioxide (sCO2) cycles will be part of the next generation of thermal power plants, especially in concentrating solar power (CSP) plants. While certain studies focus on maximizing the efficiency of these cycles in the hope of achieving a reduction in electricity costs, it is important to note that this assumption does not always hold true. This work provides a comprehensive analysis of the differences between minimizing the cost and maximizing the efficiency for the most remarkable sCO2 cycles. The analysis considers the most important physical uncertainties surrounding CSP and sCO2 cycles, such as turbine inlet temperature, ambient temperature, pressure drop and turbomachinery efficiency. Moreover, the uncertainties related to cost are also analyzed, being divided into uncertainties of sCO2 component costs and uncertainties of heating costs. The CSP system with partial cooling (sometimes with reheating and sometimes without it) is the cheapest configuration in the analyzed cases. However, the differences in cost are generally below 5% (and sometimes neglectable), while the differences in efficiency are significantly larger and below 15%. Besides the much lower efficiency of systems with simple cycle, if the heating cost is low enough, their cost could be even lower than the cost of the system with partial cooling. Systems with recompression cycles could also achieve costs below systems with partial cooling if the design's ambient temperature and the pressure drop are low.

6.
Opt Express ; 31(19): 31212-31220, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710645

RESUMO

The manufacturing and characterization of a large-size 72-electrode liquid crystal-based reconfigurable spiral phase plate (SPP) is presented. The SPP is addressed by a custom-made driver with 72 independent channels, which allows for the generation of any arbitrary integer or fractional optical vortex beam with topological charges ranging from -24 to +24. The 25 mm diameter device is fabricated using direct laser writing, leading to a fill factor over 99%. The device performance and flexibility exceed previous transparent reconfigurable SPP in terms of size, tuning range, and fill factor. The device and the light path have been simulated using the angular spectrum propagation method, showing excellent correspondence.

7.
Opt Express ; 31(23): 37653-37662, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38017891

RESUMO

A transmissive adaptable optical setup to generate a range of perfect vortex beams (PVBs) carrying different topological charges (TC) without using moving parts is presented. The setup is composed of an ad hoc transparent reconfigurable liquid crystal (LC) spiral phase plate (SPP), a refractive axicon and a convergent refractive lens. The LC SPP electrodes are manufactured ablating indium-tin oxide (ITO) glass substrates using direct laser writing (DLW) resulting in a very high fill factor device. In-house tailored electronics drive the 72 LC SPP electrodes giving rise to 72 different configurations with orbital angular momentum. In this work, the generation of PVBs with 36 positive or 36 negative TCs using this optical setup is accomplished.

8.
Phys Rev Lett ; 131(22): 226504, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101387

RESUMO

We have investigated the low-temperature local magnetic properties in the bulk of molten salt-flux (MSF)-grown single crystals of the candidate odd-parity superconductor UTe_{2} by zero-field muon spin relaxation (µSR). In contrast to previous µSR studies of UTe_{2} single crystals grown by a chemical vapor transport method, we find no evidence of magnetic clusters or electronic moments fluctuating slow enough to cause a discernible relaxation of the zero-field µSR asymmetry spectrum. Consequently, our measurements on MSF-grown single crystals rule out the generation of spontaneous magnetic fields in the bulk that would occur near impurities or lattice defects if the superconducting state of UTe_{2} breaks time-reversal symmetry. This result suggests that UTe_{2} is characterized by a single-component superconducting order parameter.

9.
Development ; 146(21)2019 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-31601548

RESUMO

A switch from E- to N-cadherin regulates the transition from pluripotency to neural identity, but the mechanism by which cadherins regulate differentiation was previously unknown. Here, we show that the acquisition of N-cadherin stabilises neural identity by dampening anti-neural signals. We use quantitative image analysis to show that N-cadherin promotes neural differentiation independently of its effects on cell cohesiveness. We reveal that cadherin switching diminishes the level of nuclear ß-catenin, and that N-cadherin also dampens FGF activity and consequently stabilises neural fate. Finally, we compare the timing of cadherin switching and differentiation in vivo and in vitro, and find that this process becomes dysregulated during in vitro differentiation. We propose that N-cadherin helps to propagate a stable neural identity throughout the emerging neuroepithelium, and that dysregulation of this process contributes to asynchronous differentiation in culture.


Assuntos
Caderinas/fisiologia , Células-Tronco Embrionárias/citologia , Neurônios/citologia , beta Catenina/fisiologia , Animais , Diferenciação Celular , Linhagem da Célula , Núcleo Celular/fisiologia , Células Cultivadas , Fatores de Crescimento de Fibroblastos/fisiologia , Camadas Germinativas/fisiologia , Camundongos , Camundongos Transgênicos , Células-Tronco Pluripotentes/citologia
10.
Endocr Pract ; 28(5): 509-514, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35247589

RESUMO

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic syndrome characterized by parathyroid, anterior pituitary, and/or duodenopancreatic neuroendocrine tumors. Studies have indicated that investigating primary hyperparathyroidism (pHPT) with subsequent genetic screening may be an essential tool for the early diagnosis of MEN1 in patients with pituitary tumors (PTs). This study aimed to investigate the presence of pHPT in patients with PTs and, subsequently, to screen for genetic mutations and related tumors in patients with MEN1 syndrome. METHODS: This study included 255 patients with PTs who were assessed for the presence of MEN1 by serum calcium and parathyroid hormone measurements. Mutation screening of the MEN1, CDKN1B, and AIP genes was performed in the index cases showing the MEN1 phenotype. RESULTS: Five patients with PTs presented a clinical condition compatible with MEN1. These patients had a younger age of onset and a more severe clinical condition. Genetic analysis identified a frameshift mutation in the MEN1 gene in one of the cases with the MEN1 phenotype, but point mutations in CDKN1B and AIP were not detected in any of these patients. CONCLUSION: Our results show that periodic screening for pHPT in patients with PTs may be useful to detect MEN1 syndrome; thus, it is recommended in those patients with both findings a genetic analysis of MEN1 gene and an additional search of related tumors. By contrast, our data suggest that CDKN1B and AIP mutations do not seem to play a relevant role in the pathogenesis of MEN1.


Assuntos
Hiperparatireoidismo Primário , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias Hipofisárias , Perfil Genético , Humanos , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/genética , Hiperparatireoidismo Primário/patologia , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/genética , Mutação , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/genética
11.
Eur J Appl Physiol ; 122(8): 1773-1795, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35362801

RESUMO

The maximal fat oxidation rate (MFO) assessed during a graded exercise test is a remarkable physiological indicator associated with metabolic flexibility, body weight loss and endurance performance. The present review considers existing biomarkers related to MFO, highlighting the validity of maximal oxygen uptake and free fatty acid availability for predicting MFO in athletes and healthy individuals. Moreover, we emphasize the role of different key enzymes and structural proteins that regulate adipose tissue lipolysis (i.e., triacylglycerol lipase, hormone sensitive lipase, perilipin 1), fatty acid trafficking (i.e., fatty acid translocase cluster of differentiation 36) and skeletal muscle oxidative capacity (i.e., citrate synthase and mitochondrial respiratory chain complexes II-V) on MFO variation. Likewise, we discuss the association of MFO with different polymorphism on the ACE, ADRB3, AR and CD36 genes, identifying prospective studies that will help to elucidate the mechanisms behind such associations. In addition, we highlight existing evidence that contradict the paradigm of a higher MFO in women due to ovarian hormones activity and highlight current gaps regarding endocrine function and MFO relationship.


Assuntos
Desempenho Atlético , Consumo de Oxigênio , Tecido Adiposo/metabolismo , Biomarcadores/metabolismo , Exercício Físico/fisiologia , Ácidos Graxos não Esterificados , Feminino , Humanos , Oxirredução , Consumo de Oxigênio/fisiologia , Polimorfismo Genético , Estudos Prospectivos , Receptores Adrenérgicos beta 3/metabolismo
12.
Int J Mol Sci ; 23(4)2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-35216459

RESUMO

Naїve CD4+ T cells, which suffer different polarizing signals during T cell receptor activation, are responsible for an adequate immune response. In this study, we aimed to evaluate the behavior of human CD4+CD45RA+ T cells after in vitro activation by anti-CD3/CD28 bead stimulation for 14 days. We also wanted to check the role of the VIP system during this process. The metabolic biomarker Glut1 was increased, pointing to an increase in glucose requirement whereas Hif-1α expression was higher in resting than in activated cells. Expression of Th1 markers increased at the beginning of activation, whereas Th17-associated biomarkers augmented after that, showing a pathogenic Th17 profile with a possible plasticity to Th17/1. Foxp3 mRNA expression augmented from day 4, but no parallel increases were observed in IL-10, IL-2, or TGFß mRNA expression, meaning that these potential differentiated Treg could not be functional. Both VIP receptors were located on the plasma membrane, and expression of VPAC2 receptor increased significantly with respect to the VPAC1 receptor from day 4 of CD4+CD45RA+ T activation, pointing to a shift in VPAC receptors. VIP decreased IFNγ and IL-23R expression during the activation, suggesting a feasible modulation of Th17/1 plasticity and Th17 stabilization through both VPAC receptors. These novel results show that, without polarizing conditions, CD4+CD45RA+ T cells differentiate mainly to a pathogenic Th17 subset and an unpaired Treg subset after several days of activation. Moreover, they confirm the important immunomodulatory role of VIP, also on naїve Th cells, stressing the importance of this neuropeptide on lymphocyte responses in different pathological or non-pathological situations.


Assuntos
Células Th17 , Peptídeo Intestinal Vasoativo , Células Cultivadas , Humanos , Antígenos Comuns de Leucócito/metabolismo , RNA Mensageiro/metabolismo , Receptores Tipo II de Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo
13.
Int J Mol Sci ; 23(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955723

RESUMO

Few studies have considered immune-mediated inflammatory disorders (IMID) together, which is necessary to adequately understand them given they share common mechanisms. Our goal was to investigate the expression of vasoactive intestinal peptide (VIP) and its receptors VPAC1 and VPAC2 in selected IMID, analyze the effect of biological therapies on them, and identify miRNA signatures associated with their expression. Serum VIP levels and mRNA of VPAC and miRNA expression in peripheral blood mononuclear cells were analyzed from 52 patients with psoriasis, rheumatoid arthritis, Graves' disease, or spondyloarthritis and from 38 healthy subjects. IMID patients showed higher levels of VIP and increased expression of VPAC2 compared to controls (p < 0.0001 and p < 0.0192, respectively). Receiver operating characteristic curve analysis showed that the levels of VIP or VPAC2 expression were adequate discriminators capable of identifying IMID. Treatment of IMID patients with anti-TNFα and anti-IL12/23 significantly affected serum VIP levels. We identified miRNA signatures associated with levels of serum VIP and VPAC2 expression, which correlated with IMID diagnosis of the patients. The results indicate that the expression of VIP/VPAC2 is able of identify IMIDs and open up a line of research based on the association between the VIP/VPAC axis and miRNA signatures in immune-mediated diseases.


Assuntos
Artrite Reumatoide , MicroRNAs , Artrite Reumatoide/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , RNA Mensageiro , Receptores Tipo II de Peptídeo Intestinal Vasoativo/metabolismo , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/genética , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/genética , Peptídeo Intestinal Vasoativo/metabolismo
14.
Hum Mol Genet ; 28(23): 4012-4021, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31630202

RESUMO

Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction and preservation of GI emptying and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.


Assuntos
Comportamento Animal/efeitos dos fármacos , Curcumina/administração & dosagem , Doença de Huntington/dietoterapia , Redução de Peso/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Curcumina/farmacologia , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Doença de Huntington/fisiopatologia , Masculino , Camundongos , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Fenótipo
15.
J Urol ; 205(5): 1344-1351, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33356482

RESUMO

PURPOSE: Genomic prognostic signatures are used on prostate biopsy tissue for cancer risk assessment, but tumor heterogeneity and multifocality may be an issue. We evaluated the variability in genomic risk assessment from different biopsy cores within the prostate using 3 prognostic signatures (Decipher, CCP, GPS). MATERIALS AND METHODS: Men in this study came from 2 prospective prostate cancer trials of patients undergoing multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy with genomic profiling of positive biopsy cores. We explored the relationship among tumor grade, magnetic resonance imaging risk and genomic risk for each signature. We evaluated the variability in genomic risk assessment between different biopsy cores and assessed how often magnetic resonance imaging targeted biopsy or the current standard of care (profiling the core with the highest grade) resulted in the highest genomic risk level. RESULTS: In all, 224 positive biopsy cores from 78 men with prostate cancer were profiled. For each signature, higher biopsy grade (p <0.001) and magnetic resonance imaging risk level (p <0.001) were associated with higher genomic scores. Genomic scores from different biopsy cores varied with risk categories changing by 21% to 62% depending on which core or signature was used. Magnetic resonance imaging targeted biopsy and profiling the core with the highest grade resulted in the highest genomic risk level in 72% to 84% and 75% to 87% of cases, respectively, depending on the signature used. CONCLUSIONS: There is variation in genomic risk assessment from different biopsy cores regardless of the signature used. Magnetic resonance imaging directed biopsy or profiling the highest grade core resulted in the highest genomic risk level in most cases.


Assuntos
Imageamento por Ressonância Magnética , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Biópsia com Agulha de Grande Calibre , Genômica , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética Multiparamétrica , Prognóstico , Estudos Prospectivos , Neoplasias da Próstata/genética , Medição de Risco/métodos
16.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208590

RESUMO

Osteoarthritis (OA) is the most common musculoskeletal disorder causing a great disability and a reduction in the quality of life. In OA, articular chondrocytes (AC) and synovial fibroblasts (SF) release innate-derived immune mediators that initiate and perpetuate inflammation, inducing cartilage extracellular matrix (ECM) degradation. Given the lack of therapies for the treatment of OA, in this study, we explore biomarkers that enable the development of new therapeutical approaches. We analyze the set of secreted proteins in AC and SF co-cultures by stable isotope labeling with amino acids (SILAC). We describe, for the first time, 115 proteins detected in SF-AC co-cultures stimulated by fibronectin fragments (Fn-fs). We also study the role of the vasoactive intestinal peptide (VIP) in this secretome, providing new proteins involved in the main events of OA, confirmed by ELISA and multiplex analyses. VIP decreases proteins involved in the inflammatory process (CHI3L1, PTX3), complement activation (C1r, C3), and cartilage ECM degradation (DCN, CTSB and MMP2), key events in the initiation and progression of OA. Our results support the anti-inflammatory and anti-catabolic properties of VIP in rheumatic diseases and provide potential new targets for OA treatment.


Assuntos
Condrócitos/metabolismo , Fibroblastos/metabolismo , Osteoartrite/metabolismo , Proteoma , Proteômica , Membrana Sinovial/citologia , Peptídeo Intestinal Vasoativo/metabolismo , Biomarcadores , Condrócitos/efeitos dos fármacos , Técnicas de Cocultura , Citocinas/metabolismo , Suscetibilidade a Doenças , Matriz Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Osteoartrite/etiologia , Osteoartrite/patologia , Proteômica/métodos , Peptídeo Intestinal Vasoativo/farmacologia
17.
Br Poult Sci ; 62(3): 387-395, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33251830

RESUMO

1. The objective of this study was to evaluate specific sensory attributes of chicken meat from different production systems to evaluate the emotional responses related to information available on the packages, as well as to investigate consumers' perceptions regarding this information.2. The survey was conducted using the Temporal Dominance of Sensations analysis, which identified differences in taste and texture between samples belonging to the organic, conventional and natural systems.3. The specific emotional lexicon for chicken meat, defined by the consumers through the EmoSemio questionnaire, provided a list of positive emotions for packages that indicated some type of information about the rearing or feeding system.4. The qualitative data obtained using the Attitude Questionnaire demonstrated that packaging and labelling are not self-explanatory, posing more doubts for the consumer at the time of purchase. It was shown that packaging and labelling were extrinsic attributes that influenced the evaluation and acceptability of products. Besides that, consumers were interested in buying products that attest to animal welfare, provided that the price is attractive.5. Poultry companies can have a greater chance of making their products more attractive if they learn more about the attitude and expectations of the consumer in relation to the products, as well as the importance of the animal welfare attributes that are communicated.


Assuntos
Galinhas , Carne , Animais , Comportamento do Consumidor , Carne/análise , Percepção , Paladar
18.
Biochem Biophys Res Commun ; 528(2): 347-358, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32145914

RESUMO

The chemokines receptor family are membrane-expressed class A-specific seven-transmembrane receptors linked to G proteins. Through interaction with the corresponding ligands, the chemokines, they induce a wide variety of cellular responses including cell polarization, movement, immune and inflammatory responses, as well as the prevention of HIV-1 infection. Like a Russian matryoshka doll, the chemokine receptor system is more complex than initially envisaged. This review focuses on the mechanisms that contribute to this dazzling complexity and how they modulate the signaling events triggered by chemokines. The chemokines and their receptors exist as monomers, dimers and oligomers, their expression pattern is highly regulated, and the ligands can bind distinct receptors with similar affinities. The use of novel imaging-based technologies, particularly real-time imaging modalities, has shed new light on the very dynamic conformations that chemokine receptors adopt depending on the cellular context, and that affect chemokine-mediated responses. This complex scenario presents both challenging and exciting opportunities for drug discovery.


Assuntos
Receptores de Quimiocinas/metabolismo , Animais , Quimiocinas/química , Quimiocinas/metabolismo , Fatores Quimiotáticos/metabolismo , Humanos , Multimerização Proteica
19.
Eur Radiol ; 30(5): 2604-2615, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32040730

RESUMO

OBJECTIVES: This study was conducted in order to establish the joint Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) guidelines on placenta accreta spectrum (PAS) disorders and propose strategies to standardize image acquisition, interpretation, and reporting for this condition with MRI. METHODS: The published evidence-based data and the opinion of experts were combined using the RAND-UCLA Appropriateness Method and formed the basis for these consensus guidelines. The responses of the experts to questions regarding the details of patient preparation, MRI protocol, image interpretation, and reporting were collected, analyzed, and classified as "recommended" versus "not recommended" (if at least 80% consensus among experts) or uncertain (if less than 80% consensus among experts). RESULTS: Consensus regarding image acquisition, interpretation, and reporting was determined using the RAND-UCLA Appropriateness Method. The use of a tailored MRI protocol and standardized report was recommended. CONCLUSIONS: A standardized imaging protocol and reporting system ensures recognition of the salient features of PAS disorders. These consensus recommendations should be used as a guide for the evaluation of PAS disorders with MRI. KEY POINTS: • MRI is a powerful adjunct to ultrasound and provides valuable information on the topography and depth of placental invasion. • Consensus statement proposed a common lexicon to allow for uniformity in MRI acquisition, interpretation, and reporting of PAS disorders. • Seven MRI features, namely intraplacental dark T2 bands, uterine/placental bulge, loss of low T2 retroplacental line, myometrial thinning/disruption, bladder wall interruption, focal exophytic placental mass, and abnormal vasculature of the placental bed, reached consensus and are categorized as "recommended" for diagnosing PAS disorders.


Assuntos
Consenso , Imageamento por Ressonância Magnética/métodos , Placenta Acreta/diagnóstico , Placenta/diagnóstico por imagem , Radiografia Abdominal/métodos , Radiologia , Sociedades Médicas , Feminino , Humanos , Gravidez
20.
Proc Natl Acad Sci U S A ; 114(21): 5384-5388, 2017 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-28487488

RESUMO

Applied pressure drives the heavy-fermion antiferromagnet CeRhIn5 toward a quantum critical point that becomes hidden by a dome of unconventional superconductivity. Magnetic fields suppress this superconducting dome, unveiling the quantum phase transition of local character. Here, we show that [Formula: see text] magnetic substitution at the Ce site in CeRhIn5, either by Nd or Gd, induces a zero-field magnetic instability inside the superconducting state. This magnetic state not only should have a different ordering vector than the high-field local-moment magnetic state, but it also competes with the latter, suggesting that a spin-density-wave phase is stabilized in zero field by Nd and Gd impurities, similarly to the case of Ce0.95Nd0.05CoIn5 Supported by model calculations, we attribute this spin-density wave instability to a magnetic-impurity-driven condensation of the spin excitons that form inside the unconventional superconducting state.

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