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Approaches to reverse or limit regulatory T cell (Treg) insufficiency are of great interest for development of immunotherapeutic treatments for autoimmune patients, including type 1 diabetes. Treg insufficiency is heavily implicated in the progression of autoimmune diabetes in the NOD mouse model and is characterized by defects in Treg numbers, development, and/or function. Utilizing a Treg-centric screen, we show that intraislet Tregs have a uniquely dysfunctional phenotype, hallmarked by an almost complete lack of neuropilin-1 (Nrp1), a cell surface receptor required to maintain Treg stability. Intraislet Nrp1- Tregs exhibit hallmark features of fragility, including reduced suppressive capacity, decreased CD73 and Helios, and increased Rorγt and Tbet. Intraislet Nrp1- Tregs also exhibit decreased Foxp3 expression on a per cell basis, suggesting that Nrp1 may also be required for long-term Treg stability. Mechanistically, Treg-restricted augmentation of Nrp1 expression limited the onset of autoimmune diabetes in NOD mice suggesting that Nrp1 critically impacts intraislet Treg function. Transcriptional analysis showed that Nrp1 restoration led to an increase in markers and pathways of TCR signaling, survival, and suppression, and when Nrp1 protein expression is examined by cellular indexing of transcriptomes and epitopes by sequencing, significant differences were observed between Nrp1+ and Nrp1- Tregs in all tissues, particularly in markers of Treg fragility. This translated into substantive differences between Nrp1+ and Nrp1- Tregs that afforded the former with a competitive advantage in the islets. Taken together, these data suggest that maintenance of Nrp1 expression and signaling on Tregs limits diabetes onset and may serve as a strategy to combat Treg insufficiency in autoimmune disease.
Assuntos
Diabetes Mellitus Tipo 1 , Neuropilina-1 , Linfócitos T Reguladores , Animais , Camundongos , Diabetes Mellitus Tipo 1/imunologia , Proteínas de Ligação a DNA , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Camundongos Endogâmicos NOD , Neuropilina-1/genética , Neuropilina-1/metabolismo , Linfócitos T Reguladores/imunologia , Fatores de TranscriçãoRESUMO
BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.
Assuntos
Anticorpos Neutralizantes , Autoanticorpos , Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Masculino , Colômbia , Feminino , Adulto , Cryptococcus gattii/imunologia , Pessoa de Meia-Idade , Cryptococcus neoformans/imunologia , Criptococose/imunologia , Criptococose/diagnóstico , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Estudos Retrospectivos , Soronegatividade para HIV/imunologia , Adulto Jovem , IdosoRESUMO
OBJECTIVES: To synthesise the dentoalveolar, periodontal and skeletal changes that occur when using maxillary expansion techniques assisted by temporary anchorage devices compared to conventional protocols. METHODS: Five databases and grey literature were consulted, up to December 2023, focusing on intervention designs and excluding other type of studies. The quality assessment was conducted by using the adaptation for orthodontics of the CONSORT statement, the guidelines for reporting non-randomised studies, the RoB-2 tool, and the ROBINS-I tool. A descriptive summary and meta-analysis using RevMan 5.4 were performed. RESULTS: Nine clinical trials were included (n=377 patients, mean age 13.2±0.6) with a diagnosis of transverse maxillary deficiency. The analysed studies showed qualitative dentoalveolar and periodontal changes after expansion, which were greater on the maxillary first premolars in tooth-borne appliances. Meta-analyses for some effects were included from two studies (n=64); patients who used tooth-borne appliances had greater effects of buccal intercoronal width between the premolars with statistically significant differences (Std Mean difference 2.34; 95% CI: 0.04-4.65 p=0.05). Conversely, those patients who used bone-borne or hybrid appliances had greater effects of buccal intercoronal width between molars with statistically significant differences (Std Mean difference -0.64; 95% CI: -1.38-0.10; p=0.09). CONCLUSIONS: According to the studies analysed, all measurements increased in the intervention groups after expansion. Quantitative analyses show different findings at dentoalveolar level when tooth-borne, bone-borne or hybrid appliances are considered. Nevertheless, the results should be taken with caution due to the heterogeneity of the studies. The protocol was registered at PROSPERO (CRD42021283170), with no funding to report.
Assuntos
Maxila , Procedimentos de Ancoragem Ortodôntica , Técnica de Expansão Palatina , Humanos , Técnica de Expansão Palatina/instrumentação , Procedimentos de Ancoragem Ortodôntica/instrumentação , Procedimentos de Ancoragem Ortodôntica/métodos , Dente Pré-Molar , AdolescenteRESUMO
Yerba Mate (YM) (Ilex paraguariensis) is a natural herbal supplement with a well-described anti-inflammatory capacity and beneficial effects in different inflammatory contexts such as insulin resistance or obesity. However, whether YM could improve other inflammatory conditions such as colitis or the immune cell population that can be modulated by this plant remains elusive. Here, by using 61 male and female C57BL/6/J wild-type (WT) mice and the dextran sodium sulfate (DSS)-induced acute colitis model, we evaluated the effect of YM on colitis symptoms and macrophage polarization. Our results showed that the oral administration of YM reduces colitis symptoms and improves animal survival. Increasing infiltration of anti-inflammatory M2 macrophage was observed in the colon of the mice treated with YM. Accordingly, YM promoted M2 macrophage differentiation in vivo. However, the direct administration of YM to bone marrow-derived macrophages did not increase anti-inflammatory polarization, suggesting that YM, through an indirect mechanism, is able to skew the M1/M2 ratio. Moreover, YM consumption reduced the Eubacterium rectale/Clostridium coccoides and Enterobacteriaceae groups and increased the Lactobacillus/Lactococcus group in the gut microbiota. In summary, we show that YM promotes an immunosuppressive environment by enhancing anti-inflammatory M2 macrophage differentiation, reducing colitis symptoms, and suggesting that YM consumption may be a good cost-effective treatment for ulcerative colitis.
Assuntos
Anti-Inflamatórios , Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Ilex paraguariensis , Macrófagos , Camundongos Endogâmicos C57BL , Extratos Vegetais , Animais , Macrófagos/efeitos dos fármacos , Ilex paraguariensis/química , Colite/tratamento farmacológico , Colite/induzido quimicamente , Masculino , Feminino , Anti-Inflamatórios/farmacologia , Camundongos , Extratos Vegetais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Modelos Animais de Doenças , Colo/efeitos dos fármacos , Colo/patologia , Diferenciação Celular/efeitos dos fármacosRESUMO
Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Autoantibodies (auto-Abs) neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera from Colombian patients with non-HIV related cryptococcosis in a retrospective national cohort collected from 1997 to 2016. Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs in 30 HIV (-) adults presenting cryptococcosis (13 by C. gattii, and 17 by C. neoformans). Results: We detected auto-Abs neutralizing GM-CSF in the plasma of 9 out of 13 (69%) patients infected with C. gattii and 1 out of 17 (6%) patients with C. neoformans. Conclusions: We report ten Colombian patients with cryptococcosis due to auto-Abs neutralizing GM-CSF. Nine of the ten patients were infected with C. gattii, and only one with C. neoformans.
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This research aimed to assess the influence of red dragon fruit peels ratio (RDF-PR) from two species, Hylocereus hybridum (HH) and Hylocereus undatus (HU), and particle size (PS) on quality parameters of red dragon fruit peel powder (RDF-PP) and its further application in emulsified alpaca-based sausages as partial substitutes of pork-back fat. A three-level full factorial design (nine treatments) was employed to evaluate the effect of RDF-PR (HH(0%):HU(100%), HH(50%):HU(50%), and HH(100%):HU(0%)) and PS (499-297, 296-177, and <177 µm) on the dependent variables: L*, a*, b*, C, h°, water-holding capacity, oil-holding capacity, swelling capacity, pectin yield, degree of esterification (analysed through FT-IR), and crude fibre content. The data analysed through a response surface methodology showed that treatment one (T1) is the best with the optimised conditions at 100% HU RDF-PR and PS of <177 µm. The statistical validation of T1 exhibited the highest water-holding capacity (32.1 g/g peel), oil-holding capacity (2.20 g oil/g peel), and pectin yield (27.1%). A completely randomised design (four formulations) was then used to assess the effect of partial replacement of pork-back fat by T1 in emulsified alpaca-based sausages on the colourimetric, physicochemical, and texture properties (hardness, chewiness, cohesiveness, springiness, adhesiveness, and adhesive force). Likewise, a sensory hedonic scale was employed to evaluate the appearance, colour, odour, flavour, texture, and overall acceptability of sausages. The results revealed that 65.7% of pork-back fat content was successfully replaced compared with a control formulation. Additionally, F3 showed significantly (p < 0.05) better colourimetric, physicochemical, and textural characteristics, such as lower hardness (34.8 N) and chewiness (21.7 N) and higher redness (a* = 19.3) and C (22.9), compared to a control formulation. This research presents RDF-PP as a promising fat substitute for developing healthier, reduced-fat meat products using fibre-rich agroindustry by-products.
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In this contribution we try to unveil the diversification process of Bothriuridae in temperate Gondwana through dated phylogenomic analyses using UCE and transcriptomics, and including in the analyses species of genera Urophonius and Cercophonius, the most closely related genera of Bothriuridae from South America and Australia respectively. Additionally we explored the hypothesis that the winter activity period of some species of Urophonius, as well as the cold environmental preferences of this genus, could be related to the climatic conditions of the time frame and area in which it evolved. Genus Urophonius was recovered as sister group to Cercophonius using amino acids and UCE. The time frame obtained for the split between South American and Australian bothriurids is 94 Ma., which suggests a dispersal event through temperate Gondwana, before the final breakup of the land bridge of South America-Antarctica-Australia ca. 35 Ma. The split between summer and winter species of Urophonius, taking place at 64 Ma, is considered representative to the turnover time from the summer activity period to the winter activity period in some species of the genus. This time frame is compatible with a period of global warming of the late Cretaceous greenhouse episode that could have triggered this change.
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Escorpiões , Animais , Filogenia , Austrália , América do Sul , Austrália do SulRESUMO
Microplastics are distributed in the environment and are considered emerging pollutants because they are not regulated by legislation. This article aims to know the current state of knowledge regarding microplastic pollution in coastal areas of Colombia. Therefore, a detailed search was carried out in databases such as Scopus, Google Scholar, and university repositories collecting scientific and academic information published between 2000 and March 2022. As a result of the review, the presence of microplastics in coastal areas of Colombia was identified, particularly in the water, sediments, and fish, thus evidencing the contamination in coastal ecosystems, where the Caribbean coast is the area with the highest amount of microplastics in sediments, especially Cartagena (249-1387 particles/m2) and Santa Marta (144-791 particles/m2). It was also found that of 302 species of fish, 7% contained microplastics in the Ciénaga Grande of Santa Marta. In the studies, on the other hand, it was observed that there is no standardized methodology; each researcher chooses a different approach according to the scientific literature. The studies showed that the most abundant microplastics were secondary microplastics, of which polypropylene and polyethylene are predominant due to their different applications in society. This review will serve as a baseline for future research on microplastics in coastal areas of Colombia and will identify the challenges and realities of the country in the face of these emerging pollutants.
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Poluentes Ambientais , Poluentes Químicos da Água , Animais , Microplásticos , Plásticos , Colômbia , Ecossistema , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Peixes , Sedimentos GeológicosRESUMO
Despite not dividing, senescent cells acquire the ability to synthesize and secrete a plethora of bioactive molecules, a feature known as the senescence-associated secretory phenotype (SASP). In addition, senescent cells often upregulate autophagy, a catalytic process that improves cell viability in stress-challenged cells. Notably, this "senescence-related autophagy" can provide free amino acids for the activation of mTORC1 and the synthesis of SASP components. However, little is known about the functional status of mTORC1 in models of senescence induced by CDK4/6 inhibitors (e.g., Palbociclib), or the effects that the inhibition of mTORC1 or the combined inhibition of mTORC1 and autophagy have on senescence and the SASP. Herein, we examined the effects of mTORC1 inhibition, with or without concomitant autophagy inhibition, on Palbociclib-driven senescent AGS and MCF-7 cells. We also assessed the pro-tumorigenic effects of conditioned media from Palbociclib-driven senescent cells with the inhibition of mTORC1, or with the combined inhibition of mTORC1 and autophagy. We found that Palbociclib-driven senescent cells display a partially reduced activity of mTORC1 accompanied by increased levels of autophagy. Interestingly, further mTORC1 inhibition exacerbated the senescent phenotype, a phenomenon that was reversed upon autophagy inhibition. Finally, the SASP varied upon inhibiting mTORC1, or upon the combined inhibition of mTORC1 and autophagy, generating diverse responses in cell proliferation, invasion, and migration of non-senescent tumorigenic cells. Overall, variations in the SASP of Palbociclib-driven senescent cells with the concomitant inhibition of mTORC1 seem to depend on autophagy.
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Senescência Celular , Piperazinas , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Piperazinas/farmacologia , Carcinogênese , AutofagiaRESUMO
Introducción: las mujeres y las personas trans que han ejercido el trabajo sexual se encuentran vulneradas puesto que son víctimas de discriminación por su condición laboral, por su género y por los riesgos que acarrea esta labor, y esto impacta en su situación de salud. Este estudio tuvo como objetivo conocer las percepciones sobre salud (física, mental y bucal) en cuatro mujeres que ejercen la prostitución en Medellín, a partir de sus experiencias de vida y aquellas relacionadas con su contexto social. Métodos: se realizó una investigación cualitativa con enfoque etnográfico para analizar las situaciones mencionadas de acuerdo con el objetivo general. Se contó con la participación de cuatro mujeres: dos de nacionalidad venezolana y dos de nacionalidad colombiana; se llevaron a cabo entrevistas semiestructuradas. Se realizó análisis de contenido cualitativo, lo cual permitió la generación de cuatro categorías (salud mental, salud bucal, salud general y calidad de vida). Resultados: sus discursos permitieron elucidar la conexión entre las condiciones de vida y la situación de salud. La falta de oportunidades laborales, un proceso migratorio de profundos cambios económicos y sociales, y una Colombia con inequidades y barreras de acceso a servicios de salud y sociales, son procesos determinantes de orden general, particular y singular de las precarias condiciones de salud bucal y general. Conclusiones: la población participante se encuentra en situación de vulnerabilidad social y de salud, lo cual evidencia la necesidad de políticas públicas y estrategias basadas en la realidad social que contribuyan a generar equidad en salud.
Introduction: women and trans people who have engaged in sex work are triply vulnerable since they are victims of discrimination due to their employment status, their gender, and the risks that this work entails, this impacts their health situation. This study aimed to know the perceptions about health (physical, mental, and oral) of four women who work in prostitution in Medellin, based on their life experiences and those related to their social context. Methods: qualitative research with an ethnographic approach was conducted to analyze the situations mentioned. Four women participated, two Venezuelans and two Colombians, and semi-structured interviews were conducted. Qualitative content analysis was performed, which allowed the generation of four categories (mental health, oral health, general health, and quality of life). Results: her discourses made it possible to elucidate the connection between the living conditions and the health situation. Lack of job opportunities, a migratory process of profound economic and social changes, and a Colombia with inequities and barriers to access to health and social services are determining processes of a general and singular order of the precarious conditions of oral health and general. Conclusions: the participating population is in a situation of social and health vulnerability, which shows the need for public policies and strategies based on the social reality that contribute to generating equity in health.