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1.
Int J Mol Sci ; 25(10)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38791357

RESUMO

The lung is prone to infections from respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A challenge in combating these infections is the difficulty in targeting antiviral activity directly at the lung mucosal tract. Boosting the capability of the respiratory mucosa to trigger a potent immune response at the onset of infection could serve as a potential strategy for managing respiratory infections. This study focused on screening immunomodulators to enhance innate immune response in lung epithelial and immune cell models. Through testing various subfamilies and pathways of pattern recognition receptors (PRRs), the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family was found to selectively activate innate immunity in lung epithelial cells. Activation of NOD1 and dual NOD1/2 by the agonists TriDAP and M-TriDAP, respectively, increased the number of IL-8+ cells by engaging the NF-κB and interferon response pathways. Lung epithelial cells showed a stronger response to NOD1 and dual NOD1/2 agonists compared to control. Interestingly, a less-pronounced response to NOD1 agonists was noted in PBMCs, indicating a tissue-specific effect of NOD1 in lung epithelial cells without inducing widespread systemic activation. The specificity of the NOD agonist pathway was confirmed through gene silencing of NOD1 (siRNA) and selective NOD1 and dual NOD1/2 inhibitors in lung epithelial cells. Ultimately, activation induced by NOD1 and dual NOD1/2 agonists created an antiviral environment that hindered SARS-CoV-2 replication in vitro in lung epithelial cells.


Assuntos
COVID-19 , Células Epiteliais , Pulmão , Proteína Adaptadora de Sinalização NOD1 , SARS-CoV-2 , Humanos , Células A549 , Antivirais/farmacologia , COVID-19/imunologia , COVID-19/virologia , Tratamento Farmacológico da COVID-19 , Ácido Diaminopimélico/análogos & derivados , Ácido Diaminopimélico/farmacologia , Células Epiteliais/virologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Imunidade Inata/efeitos dos fármacos , Interleucina-8/metabolismo , Pulmão/imunologia , Pulmão/virologia , Pulmão/metabolismo , NF-kappa B/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Adaptadora de Sinalização NOD1/agonistas , Proteína Adaptadora de Sinalização NOD2/agonistas , Proteína Adaptadora de Sinalização NOD2/metabolismo , SARS-CoV-2/fisiologia , SARS-CoV-2/imunologia , Transdução de Sinais/efeitos dos fármacos
3.
J Viral Hepat ; 30(1): 56-63, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36197907

RESUMO

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.


Assuntos
Hepatite C Crônica , Hepatite C , Humanos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , América Latina/epidemiologia , Perda de Seguimento , Hepacivirus/genética , Organização Mundial da Saúde
4.
Arch. pediatr. Urug ; 94(2): e602, 2023.
Artigo em Espanhol | LILACS, UY-BNMED, BNUY | ID: biblio-1520100

RESUMO

El artículo aborda un tema particularmente sensible para la investigación científica como lo son los estudios que involucran directamente a niños y niñas. El valor social y la relevancia científica de la investigación en este campo es indudable, sin embargo, su justificación requiere especial detenimiento en las condiciones para el ejercicio de sus derechos antes, durante y después del proceso de investigación. La naturalización de su denominación como "población vulnerable" y el ejercicio de su autonomía relativa, son dos dimensiones principales aquí. El artículo navega por preguntas que no se resuelven aquí precisamente, ¿qué garantías para el proceso efectivo de asentimiento informado?, ¿cómo acompañar en la toma de decisiones sin sustituir al niño y la niña? Sin embargo, sí avanza en la instalación de dilemas y aspectos conceptuales y reflexivos sustantivos en la práctica científica.


The article deals with a particularly sensitive topic for scientific research, such as research studies that directly involve boys and girls. The social value and scientific relevance of research in this field is unquestionable; however, its justification requires special care regarding the conditions of children's rights before, during and after the research process. The naturalization of their denomination as a "vulnerable population" and the exercise of their relative autonomy are the two main dimensions of this study. This paper explores questions that are not answered in it precisely: what guarantees informed consent during the effective process? How to accompany the decision making process without replacing the boy and the girl? However, the study makes progress regarding the setting of substantive conceptual and reflective dilemmas and aspects in scientific practice.


O artigo trata de um tema particularmente sensível para a pesquisa científica, os estudos que envolvem diretamente meninos e meninas. O valor social e a relevância científica da pesquisa neste campo é inquestionável, porém, sua justificativa requer cuidados especiais nas condições de exercício dos direitos da criancas, durante e após o processo de pesquisa. A naturalização de sua denominação como "população vulnerável" e o exercício de sua autonomia relativa são as duas dimensões principais deste paper. O artigo explora por questões que não são aqui resolvidas de forma precisa: quais sao as garantias para o processo efetivo de assentimento informado? Como acompanhar o proceso da tomada de decisões sem substituir o menino e a menina? No entanto, realizamos um avanço na instalação de dilemas e aspectos conceituais e reflexivos substantivos na prática científica.


Assuntos
Humanos , Criança , Ética em Pesquisa , Consentimento Informado por Menores/ética
5.
Front Immunol ; 13: 1055042, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561760

RESUMO

Preventing new HIV infections remains a global challenge. Young women continue to bear a disproportionate burden of infection. Oral pre-exposure prophylaxis (PrEP), offers a novel women-initiated prevention technology and PrEP trials completed to date underscore the importance of their inclusion early in trials evaluating new HIV PrEP technologies. Data from completed topical and systemic PrEP trials highlight the role of gender specific physiological and social factors that impact PrEP uptake, adherence and efficacy. Here we review the past and current developments of HIV-1 prevention options for women with special focus on PrEP considering the diverse factors that can impact PrEP efficacy. Furthermore, we highlight the importance of inclusion of female scientists, clinicians, and community advocates in scientific efforts to further improve HIV prevention strategies.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Profilaxia Pré-Exposição , Humanos , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/tratamento farmacológico
6.
Front Immunol ; 13: 993401, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304456

RESUMO

Intravesical BCG instillation after bladder tumor resection is the standard treatment for non-muscle invasive bladder cancer; however, it is not always effective and frequently has undesirable side effects. Therefore, new strategies that improve the clinical management of patients are urgently needed. This study aimed to comprehensively evaluate the bladder tumor immune microenvironment profile after intravesical treatment with a panel of mycobacteria with variation in their cell envelope composition and its impact on survival using an orthotopic murine model to identify more effective and safer therapeutic strategies. tumor-bearing mice were intravesically treated with a panel of BCG and M. brumae cultured under different conditions. Untreated tumor-bearing mice and healthy mice were also included as controls. After mycobacterial treatments, the infiltrating immune cell populations in the bladder were analysed by flow cytometry. We provide evidence that mycobacterial treatment triggered a strong immune infiltration into the bladder, with BCG inducing higher global absolute infiltration than M. brumae. The induced global immune microenvironment was strikingly different between the two mycobacterial species, affecting both innate and adaptive immunity. Compared with M. brumae, BCG treated mice exhibited a more robust infiltration of CD4+ and CD8+ T-cells skewed toward an effector memory phenotype, with higher frequencies of NKT cells, neutrophils/gMDSCs and monocytes, especially the inflammatory subset, and higher CD4+ TEM/CD4+ Treg and CD8+ TEM/CD4+ Treg ratios. Conversely, M. brumae treatment triggered higher proportions of total activated immune cells and activated CD4+ and CD8+ TEM cells and lower ratios of CD4+ TEM cells/CD4+ Tregs, CD8+ TEM cells/CD4+ Tregs and inflammatory/reparative monocytes. Notably, the mycobacterial cell envelope composition in M. brumae had a strong impact on the immune microenvironment, shaping the B and myeloid cell compartment and T-cell maturation profile and thus improving survival. Overall, we demonstrate that the bladder immune microenvironment induced by mycobacterial treatment is species specific and shaped by mycobacterial cell envelope composition. Therefore, the global bladder immune microenvironment can be remodelled, improving the quality of infiltrating immune cells, the balance between inflammatory and regulatory/suppressive responses and increasing survival.


Assuntos
Mycobacterium , Neoplasias da Bexiga Urinária , Camundongos , Animais , Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Linfócitos T CD8-Positivos , Vacina BCG/uso terapêutico , Microambiente Tumoral
7.
Sci Rep ; 12(1): 7439, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523829

RESUMO

A complex link exists between HIV-1 and autophagy, and discordant results have been reported in different in vitro models regarding the way HIV and autophagy modulate each other. Despite this, there is very limited knowledge about the interplay between HIV and autophagy in vivo in lymphoid tissue, due in part by the lack of cell models that recapitulate the in vivo setting. Here, we evaluate the interrelationship between HIV and autophagy using human ex vivo lymphoid tissue cultures as an HIV infection model. Our results showed that human lymphoid aggregated cultures (HLACs) from tonsillar tissue displayed fully functional autophagic activity. In this system, HIV infection resulted in an increase in autophagy. Notably, we observed that both, autophagy-enhancing (rapamycin) or blocking drugs (3-methyladenine, chloroquine and bafilomycin), were able to decrease HIV-DNA levels and HIV replication. Therefore, efficient HIV-1 replication requires a fine-tuned level of autophagy, so modifications of this balance will have a negative impact on its replication. Therefore, targeting the autophagic pathway could be a new therapeutic approach to be explored to treat HIV-1 infection. Ex vivo cultures of human lymphoid tissue are a suitable model to obtain further insights into HIV and its intricate relationship with autophagy.


Assuntos
Infecções por HIV , HIV-1 , Autofagia , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Tecido Linfoide , Replicação Viral
8.
Oncoimmunology ; 11(1): 2051845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355681

RESUMO

The mechanism of action of intravesical Mycobacterium bovis BCG immunotherapy treatment for bladder cancer is not completely known, leading to misinterpretation of BCG-unresponsive patients, who have scarce further therapeutic options. BCG is grown under diverse culture conditions worldwide, which can impact the antitumor effect of BCG strains and could be a key parameter of treatment success. Here, BCG and the nonpathogenic Mycobacterium brumae were grown in four culture media currently used by research laboratories and BCG manufacturers: Sauton-A60, -G15 and -G60 and Middlebrook 7H10, and used as therapies in the orthotopic murine BC model. Our data reveal that each mycobacterium requires specific culture conditions to induce an effective antitumor response. since higher survival rates of tumor-bearing mice were achieved using M. brumae-A60 and BCG-G15 than the rest of the treatments. M. brumae-A60 was the most efficacious among all tested treatments in terms of mouse survival, cytotoxic activity of splenocytes against tumor cells, higher systemic production of IL-17 and IFN-É£, and bladder infiltration of selected immune cells such as ILCs and CD4TEM. BCG-G15 triggered an antitumor activity based on a massive infiltration of immune cells, mainly CD3+ (CD4+ and CD8+) T cells, together with high systemic IFN-É£ release. Finally, a reduced variety of lipids was strikingly observed in the outermost layer of M. brumae-A60 and BCG-G15 compared to the rest of the cultures, suggesting an influence on the antitumor immune response triggered. These findings contribute to understand how mycobacteria create an adequate niche to help the host subvert immunosuppressive tumor actions.


Assuntos
Mycobacterium bovis , Neoplasias da Bexiga Urinária , Animais , Humanos , Imunoterapia , Interleucina-17 , Camundongos , Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico
9.
Dis Model Mech ; 15(3)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35344038

RESUMO

Cancer continues to be a leading cause of death worldwide, largely due to metastases and cachexia. It is a complex disease that is commonly associated with a variety of comorbidities. With global increases in ageing populations and obesity, multimorbidity is a rapidly growing clinical issue in the context of cancer. Cancer is also genetically heterogeneous, with a tumour's unique profile determining its incidence of metastasis, degree of cachexia and response to therapeutics. These complexities of human cancer are difficult to replicate in animal models and are, in part, responsible for the failures in translational cancer research. In this Perspective, we highlight the fruit fly, Drosophila melanogaster, as a powerful model organism to investigate multimorbidity and tumour diversity. We also highlight how harnessing these complexities in Drosophila can, potentially, enhance cancer research and advance therapeutic discoveries.


Assuntos
Drosophila , Neoplasias , Animais , Caquexia , Modelos Animais de Doenças , Drosophila melanogaster/fisiologia , Neoplasias/complicações
10.
Antioxidants (Basel) ; 10(12)2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34943007

RESUMO

The aim of this study was to develop a new hybrid biomaterial that could photo-stabilize and improve the photoprotective capacity of a Baccharis antioquensis extract. Different combinations of lignin/gelatin/natural extract were applied to prepare hybrid biomaterial nanoparticles (NPs), which were then incorporated into an emulsion. The in vitro photoprotection and photostability were evaluated. The methanolic extract showed high phenolic content (646.4 ± 9.5 mg GAE/g dry extract) and a DPPH radical assay revealed that the antiradical capacity of the extract (0.13 to 0.05 g extract/mmol DPPH) was even better than that of BHT. The particle size of the hybrid biomaterial ranged from 100 to 255 nm; a polydispersity index (PdI) between 0.416 and 0.788 is suitable for topical use in dermocosmetic products. The loading capacity of the extract ranged from 27.0 to 44.5%, and the nanoparticles (NPs) showed electrostatic stability in accordance with the zeta potential value. We found that the formulation based on lignin: extract (1:1 ratio) and gelatin: lignin: extract (0.5:0.5:1 ratio) demonstrated photoprotection qualities with a sun protection factor (SPF) ranging from 9.4 to 22.6. In addition, all the hybrid NP-formulations were time-stable with %SPFeff and %UVAPFeff greater than 80% after exposure to 2 h of radiation. These results suggest that the hybrid biopolymer-natural extract improved the photoprotection and photostability properties, as well as the antiradical capacity, of the B. antioquensis extract, and may be useful for trapping high polyphenol content from natural extracts, with potential application in cosmeceutical formulations.

11.
Viruses ; 13(9)2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34578296

RESUMO

Angiotensin converting enzyme 2 (ACE2) is a host ectopeptidase and the receptor for the SARS-CoV-2 virus, albeit virus-ACE2 interaction goes far beyond viral entry into target cells. Controversial data exists linking viral infection to changes in ACE2 expression and function, which might influence the subsequent induction of an inflammatory response. Here, we tested the significance of soluble ACE2 enzymatic activity longitudinally in nasopharyngeal swabs and plasma samples of SARS-CoV-2 infected patients, along with the induction of inflammatory cytokines. Release of soluble functional ACE2 increases upon SARS-CoV-2 infection in swabs and plasma of infected patients, albeit rapidly decreasing during infection course in parallel with ACE2 gene expression. Similarly, SARS-CoV-2 infection also induced the expression of inflammatory cytokines. These changes positively correlated with the viral load. Overall, our results demonstrate the existence of mechanisms by which SARS-CoV-2 modulates ACE2 expression and function, intracellular viral sensing and subsequent inflammatory response, offering new insights into ACE2 dynamics in the human upper respiratory tract and pointing towards soluble ACE2 levels as a putative early biomarker of infection severity.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/virologia , Interações Hospedeiro-Patógeno , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/genética , Biomarcadores , COVID-19/diagnóstico , COVID-19/imunologia , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Expressão Gênica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , SARS-CoV-2/isolamento & purificação , Carga Viral
12.
Front Microbiol ; 12: 661446, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995324

RESUMO

HIV/AIDS is still a global threat despite the notable efforts made by the scientific and health communities to understand viral infection, to design new drugs or to improve existing ones, as well as to develop advanced therapies and vaccine designs for functional cure and viral eradication. The identification and analysis of HIV-1 positive individuals that naturally control viral replication in the absence of antiretroviral treatment has provided clues about cellular processes that could interact with viral proteins and RNA and define subsequent viral replication and clinical progression. This is the case of autophagy, a degradative process that not only maintains cell homeostasis by recycling misfolded/old cellular elements to obtain nutrients, but is also relevant in the innate and adaptive immunity against viruses, such as HIV-1. Several studies suggest that early steps of HIV-1 infection, such as virus binding to CD4 or membrane fusion, allow the virus to modulate autophagy pathways preparing cells to be permissive for viral infection. Confirming this interplay, strategies based on autophagy modulation are able to inhibit early steps of HIV-1 infection. Moreover, autophagy dysregulation in late steps of the HIV-1 replication cycle may promote autophagic cell-death of CD4+ T cells or control of HIV-1 latency, likely contributing to disease progression and HIV persistence in infected individuals. In this scenario, understanding the molecular mechanisms underlying HIV/autophagy interplay may contribute to the development of new strategies to control HIV-1 replication. Therefore, the aim of this review is to summarize the knowledge of the interplay between autophagy and the early events of HIV-1 infection, and how autophagy modulation could impair or benefit HIV-1 infection and persistence, impacting viral pathogenesis, immune control of viral replication, and clinical progression of HIV-1 infected patients.

13.
Front Immunol ; 11: 582330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329554

RESUMO

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmune disorder characterized by numerous symptoms of unknown etiology. The ME/CFS immune markers reported so far have failed to generate a clinical consensus, perhaps partly due to the limitations of biospecimen biobanking. To address this issue, we performed a comparative analysis of the impact of long-term biobanking on previously identified immune markers and also explored additional potential immune markers linked to infection in ME/CFS. A correlation analysis of marker cryostability across immune cell subsets based on flow cytometry immunophenotyping of fresh blood and frozen PBMC samples collected from individuals with ME/CFS (n = 18) and matched healthy controls (n = 18) was performed. The functionality of biobanked samples was assessed on the basis of cytokine production assay after stimulation of frozen PBMCs. T cell markers defining Treg subsets and the expression of surface glycoprotein CD56 in T cells and the frequency of the effector CD8 T cells, together with CD57 expression in NK cells, appeared unaltered by biobanking. By contrast, NK cell markers CD25 and CD69 were notably increased, and NKp46 expression markedly reduced, by long-term cryopreservation and thawing. Further exploration of Treg and NK cell subsets failed to identify significant differences between ME/CFS patients and healthy controls in terms of biobanked PBMCs. Our findings show that some of the previously identified immune markers in T and NK cell subsets become unstable after cell biobanking, thus limiting their use in further immunophenotyping studies for ME/CFS. These data are potentially relevant for future multisite intervention studies and cooperative projects for biomarker discovery using ME/CFS biobanked samples. Further studies are needed to develop novel tools for the assessment of biomarker stability in cryopreserved immune cells from people with ME/CFS.


Assuntos
Biomarcadores/metabolismo , Células Sanguíneas/metabolismo , Síndrome de Fadiga Crônica/diagnóstico , Células Matadoras Naturais/metabolismo , Subpopulações de Linfócitos/metabolismo , Linfócitos T/metabolismo , Adulto , Estudos de Casos e Controles , Células Cultivadas , Estudos de Coortes , Criopreservação , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Food Sci Technol Int ; 26(2): 160-172, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31547687

RESUMO

Gluten-free breads were developed by incorporating unripe banana flour in a blend of alternative flour/cassava starch, 45/50. A factorial design was applied to determine the simultaneous effect of percentage of unripe banana flour (2, 8, 15%) and the type of alternative flour (quinoa, oyster mushroom, yellow pea and lentil flour) on structural and colour properties of bread. Principal component analysis was used to evaluate the behaviour of the formulations from a comprehensive perspective. Three formulations, denoted as P8 (pea + 8% unripe banana flour), Q15 (quinoa + 15% unripe banana flour) and L15 (lentil + 15% unripe banana flour) exhibited the closest profiles to reference (wheat bread). Breads with oyster mushroom flour showed a profile significantly different from the rest of formulations. The interactions among the factors were significant for all studied properties and showed that the unripe banana flour fortification did not lead to proportional responses on the bread properties, but the behaviour of unripe banana flour in breadmaking relied on the percentage and the type of alternative flour used. The P8, Q15 and L15 exhibited high fibre content and carbohydrate content lower than the reference. In addition, P8 formulation can be classified as intermediate glycaemic index.


Assuntos
Pão/análise , Farinha/análise , Musa/química , Chenopodium quinoa/química , Cor , Fibras na Dieta/análise , Análise de Alimentos , Manipulação de Alimentos , Glutens/análise , Índice Glicêmico , Análise de Componente Principal , Amido/química , Triticum/química
15.
Microbiol Resour Announc ; 8(40)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582442

RESUMO

Actinobacteriophage Finny contains a circularly permuted 40,313-bp double-stranded DNA genome with 63 predicted protein-coding genes. Finny was directly isolated from a soil sample collected in New Braunfels, Texas, that was incubated with Microbacterium foliorum SEA B-24224. Finny is closely related to bacteriophages MCubed, Andromedas, ColaCorta, Eleri, and Sansa.

16.
Oncoimmunology ; 8(8): 1602460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413912

RESUMO

Intravesical Bacille Calmette-Guérin (BCG) remains the most effective treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), unfortunately there is no validated biomarker to predict clinical outcome. Here we tried to explore the possibility that a combination of the density of peritumoral infiltrating cells (Th1, Th2 and PD-L1) and the composition of peripheral immune cells (neutrophil and lymphocyte counts) could generate a more reliable prognostic biomarker. Twenty-two patients with high-risk NMIBC treated with BCG (10 BCG nonresponders and 12 BCG responders) were selected. BCG responders had significantly lower level of peritumoral T-bet+ cells with an associated higher GATA-3+/T-bet+ ratio (p = 0.04, p = 0.02, respectively). Furthermore, the immune polarization in tissue (GATA-3+/T-bet+ ratio) adjusted for the systemic inflammation (neutrophil-to-lymphocyte ratio) showed a significantly higher association with the BCG response (p = 0.004). A survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with a lower T-bet+/Lymphocyte ratio and higher GTR/NLR (p = 0.01). No association was observed between peritumoral PD-L1+ expression and the BCG response. In conclusion, alterations in overall immune function, both local and systemic, may influence the therapeutic response to BCG, therefore a combined analysis of tumoral (Th2/Th1 ratio) and peripheral (NLR) immune composition prior to treatment may be a promising approach to predict the BCG response in high-risk NMIBC patients.

17.
Rev. lasallista investig ; 16(1): 93-102, ene.-jun. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1094016

RESUMO

Resumen Introducción: el café verde es un producto del mercado mundial cuyo precio es determinado por sus características sensoriales en taza; sin embargo, estos atributos cambian durante el almacenamiento, convirtiendo esta etapa de la cadena productiva en una etapa crucial para garantizar la calidad del producto. Objetivo: en este trabajo se buscó determinar el impacto de diversos factores de almacenamiento en la calidad sensorial y física del café verde colombiano, bajo condiciones de estabilidad acelerada y natural. Materiales y métodos: cerezas maduras de café de la misma cosecha fueron procesadas en paralelo por dos métodos postcosecha para obtener café lavado y semilavado, después se sometieron a diferentes tratamientos de almacenamiento. Resultados: el café verde almacenado en condiciones ambientales presentó notas propias de reposo, la densidad y los parámetros del color cambiaron de diferente manera en los dos tipos de café. El comportamiento del café verde en almacenamiento acelerado varió en función de los métodos de beneficio; en el café lavado, el almacenamiento con humedad afecto los atributos sensoriales y alteró la densidad, el % HR y los parámetros de color L* y b*; en el café semilavado, el oxígeno fue el factor de mayor impacto, afectando también la densidad y el color. Conclusiones: diferentes métodos de beneficio de café no solo dan lugar a diferencias en los perfiles de la calidad sensorial, sino que también condicionan el comportamiento del grano de café verde durante el almacenamiento.


Abstract Introduction: Green coffee i s a product of the world market whose price is determined by its sensory characteristics in the cup; however, these attributes change during storage, turning this stage of the production chain into a crucial stage to guarantee product quality. Objective: In the present work we sought to determine the impact of various storage factors on the sensory and physical quality of Colombian green coffee, under conditions of accelerated and natural stability. Materials and methods: Mature coffee cherries from the same harvest were processed in parallel by two post-harvest methods to obtain washed and semi-washed coffee, and then they were subjected to different storage treatments. Results: It was found that green coffee stored under environmental conditions had the characteristic notes of rest; in addition, density and color parameters changed differently in the two types of coffee. The behavior of green coffee in accelerated storage treatments varied according to the processing methods. For the case of washed coffee, storage with humidity negatively affected sensory attributes and also altered density, the RH % and color parameters L* and b*; for the semi-washed coffee, oxygen was the factor that promoted the greatest sensory changes, also affecting density and color. Conclusions: Different coffee post-harvest processes not only give rise to differences in the profiles of sensory quality but also condition the behavior of green coffee bean during storage.


Resumo Introdução: O café verde é um produto do mercado mundial cuj o preço é determinado pelas suas características sensoriais na xícara; no entanto, estes atributos mudam durante o armazenamento, tornando esta etapa da cadeia produtiva em uma etapa crucial para garantir a qualidade do produto. Objetivo: em este trabalho se procura determinar o impacto de diversos fatores de armazenamento na qualidade sensorial e física do café verde colombiano, sob condições de estabilidade acelerada e natural. Materiais e métodos: cerejas maduras do café da mesma colheita foram processadas em paralelo pelos métodos pós-colheita para obter café lavado e semi-lavado, despois someteram-se a diferentes tratamentos de armazenamento. Resultados: o café verde armazenado em condições ambientais apresentou notas próprias de repouso, a densidade e os parâmetros da color mudaram de diferente maneira nos dois tipos de café. O comportamento do café verde em armazenamento acelerado variou em função dos métodos de benefício; no café lavado, o armazenamento com umidade afetou os atributos sensoriais e alterou a densidade, o %HR e os parâmetros da color L* e b*; no café semi-lavado, o oxigénio foi o fator de maior impacto, afetando também a densidade e a color. Conclusões: diferentes processos de pós-colheita do café não só produziriam diferenças nos perfis de qualidade sensorial, mas também condicionam o comportamento do grão de café verde durante o armazenamento.

18.
Sci Rep ; 9(1): 5544, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944395

RESUMO

In untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4+ T cell counts. HIV-1 envelope glycoprotein complex (Env) is a major cytopathic determinant in viral replication; therefore, we have deeply characterized Env function in this rare clinical phenotype. Full-length Env clones isolated from individuals with Viral Load (VL) > 10,000 copies/mL classified as VNPs (n = 15) or rapid progressors (RPs, n = 17) were geno- and phenotypically analyzed by determining diversity, expression, CD4 binding/signaling, fusogenicity, infectivity and autophagy induction. Selected Env clones from VNPs and RPs (n = 32) showed similar expression, fusion and infection abilities. Env clones from both groups showed similar affinity for CD4 during cell-to-cell transmission and consistently induced similar levels of CD4 signaling, measured by α-tubulin acetylation. Moreover, we demonstrate for the first time that primary Env clones from VNP and RP induce autophagy in uninfected cells and that this feature correlated with fusogenic capacity but was unrelated to disease progression. In conclusion, our data suggest that Env clones from VNP individuals are fully functional. Therefore, the paradoxical CD4+ T cell count stability coexisting with high levels of viral replication is unrelated to Env function.


Assuntos
Infecções por HIV/virologia , HIV-1/genética , Viremia/virologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo , Autofagia/fisiologia , Antígenos CD4/metabolismo , Linfócitos T CD4-Positivos/virologia , Regulação Viral da Expressão Gênica , Células HEK293 , Infecções por HIV/etiologia , HIV-1/patogenicidade , HIV-1/fisiologia , Humanos , Viremia/etiologia , Replicação Viral , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
19.
In. CASMU. Investigación clínica: desarrollo e innovación, 2019. Montevideo, Ideas Uruguay, 2019. p.212-212.
Monografia em Espanhol | LILACS, UY-BNMED, BNUY | ID: biblio-1359617
20.
Rehabil. integral (Impr.) ; 13(2): 74-85, Diciembre 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-986468

RESUMO

Introducción: El proceso de adaptación a la situación de discapacidad y la identidad, son variables psicológicas que pueden incidir en la participación e inclusión social de jóvenes en situación de discapacidad y que han sido poco estudiadas en nuestro país. Objetivo: Analizar las experiencias de vida que los jóvenes con parálisis cerebral (PC) destacan en su adaptación a la situación de discapacidad y su construcción de identidad. Método: Estudio cualitativo de análisis de contenido con enfoque biográfico, en una muestra intencionada de 5 jóvenes con diagnóstico de PC, sin compromiso cognitivo, entre 18 y 21 años de edad, usuarios activos de Teletón. Resultados: Las experiencias asociadas a estrategias parentales, participación con pares, procedimientos invasivos en la rehabilitación inciden en el proceso de construcción de identidad y la adaptación a la situación de discapacidad. La adaptación aparece como un proceso fluctuante a lo largo del desarrollo evolutivo, con componentes afectivos y cognitivos. Conclusiones: El proceso de adaptación a la situación de discapacidad progresa hacia construir significados trascendentales y positivos sobre sí mismos. Los resultados sugieren la necesidad de diseñar intervenciones de apoyo en periodos críticos del desarrollo psicológico para promover el bienestar de usuarios de servicios de rehabilitación integrales.


Adaptation and identity construction of young people with cerebral palsy. A qualitative study with a biographical approach Introduction: The psychological process of adaptation to disability and personal identity has an influence on social participation and inclusion of young people with disabilities; however it has been poorly researched in Chile. Objective: To analyze life experiences that young people with cerebral palsy (CP) highlight in their process of adapting to disability and identity construction. Method: Qualitative study of content analysis with a biographical approach, in an intentional sample of 5 young people diagnosed with CP, without cognitive impairment, ages ranging from 19 to 21 years, active users of Teletón Institute. Results: The experience related to parental strategies, relationship with peers, invasive procedures during the rehabilitation process, have an incidence on the processes of identity construction and adaptation to the disability. Adaptation appears as a process with fluctuations in intensity throughout the evolutionary development with emotional and cognitive components. Conclusions: The process of adaptation to the disability progresses to the construction of relevant and positive significance about themselves. The results suggest the need to design interventions to provide support in critical periods of psychological development in order to promote the wellbeing of the users of integral rehabilitations services.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Identificação Social , Paralisia Cerebral/psicologia , Pessoas com Deficiência/psicologia , Adaptação Psicológica , Pesquisa Qualitativa , Participação Social
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