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1.
Cell ; 157(2): 340-356, 2014 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-24725403

RESUMEN

Innate lymphoid cells (ILCs) are a recently recognized group of lymphocytes that have important functions in protecting epithelial barriers against infections and in maintaining organ homeostasis. ILCs have been categorized into three distinct groups, transcriptional circuitry and effector functions of which strikingly resemble the various T helper cell subsets. Here, we identify a common, Id2-expressing progenitor to all interleukin 7 receptor-expressing, "helper-like" ILC lineages, the CHILP. Interestingly, the CHILP differentiated into ILC2 and ILC3 lineages, but not into conventional natural killer (cNK) cells that have been considered an ILC1 subset. Instead, the CHILP gave rise to a peculiar NKp46(+) IL-7Rα(+) ILC lineage that required T-bet for specification and was distinct of cNK cells or other ILC lineages. Such ILC1s coproduced high levels of IFN-γ and TNF and protected against infections with the intracellular parasite Toxoplasma gondii. Our data significantly advance our understanding of ILC differentiation and presents evidence for a new ILC lineage that protects barrier surfaces against intracellular infections.


Asunto(s)
Diferenciación Celular , Linfocitos/citología , Linfocitos/inmunología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Factor de Transcripción GATA3/metabolismo , Inmunidad Innata , Proteína 2 Inhibidora de la Diferenciación/metabolismo , Ratones , Ratones Endogámicos C57BL , Receptores de Interleucina-7/metabolismo , Células Madre/citología , Toxoplasma , Toxoplasmosis/inmunología
2.
Immunity ; 51(5): 871-884.e6, 2019 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-31628054

RESUMEN

Group 3 innate lymphoid cells (ILC3s) sense environmental signals that are critical for gut homeostasis and host defense. However, the metabolite-sensing G-protein-coupled receptors that regulate colonic ILC3s remain poorly understood. We found that colonic ILC3s expressed Ffar2, a microbial metabolite-sensing receptor, and that Ffar2 agonism promoted ILC3 expansion and function. Deficiency of Ffar2 in ILC3s decreased their in situ proliferation and ILC3-derived interleukin-22 (IL-22) production. This led to impaired gut epithelial function characterized by altered mucus-associated proteins and antimicrobial peptides and increased susceptibility to colonic injury and bacterial infection. Ffar2 increased IL-22+ CCR6+ ILC3s and influenced ILC3 abundance in colonic lymphoid tissues. Ffar2 agonism differentially activated AKT or ERK signaling and increased ILC3-derived IL-22 via an AKT and STAT3 axis. Our findings suggest that Ffar2 regulates colonic ILC3 proliferation and function, and they identify an ILC3-receptor signaling pathway modulating gut homeostasis and pathogen defense.


Asunto(s)
Inmunidad Innata , Inmunidad Mucosa , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Linfocitos/inmunología , Linfocitos/metabolismo , Receptores de Superficie Celular/metabolismo , Animales , Biomarcadores , Citocinas/metabolismo , Susceptibilidad a Enfermedades , Microbioma Gastrointestinal/inmunología , Expresión Génica , Humanos , Inmunomodulación , Mucosa Intestinal/patología , Activación de Linfocitos/inmunología , Ratones , Ratones Noqueados , Proteínas Proto-Oncogénicas c-akt , Receptores de Superficie Celular/agonistas , Factor de Transcripción STAT3/metabolismo
3.
Immunity ; 47(3): 435-449.e8, 2017 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-28930659

RESUMEN

Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs. Moreover, the Rroid locus, but not the lncRNA itself, controlled the identity and function of ILC1s by promoting chromatin accessibility and deposition of STAT5 at the promoter of Id2 in response to interleukin (IL)-15. Thus, non-coding elements responsive to extracellular cues unique to each ILC subset represent a key regulatory layer for controlling the identity and function of ILCs.


Asunto(s)
Regulación de la Expresión Génica , Inmunidad Innata/genética , Linfocitos/metabolismo , ARN Largo no Codificante/genética , Secuencias Reguladoras de Ácidos Nucleicos , Animales , Diferenciación Celular , Linaje de la Célula/genética , Linaje de la Célula/inmunología , Ensamble y Desensamble de Cromatina , Femenino , Perfilación de la Expresión Génica , Sitios Genéticos , Homeostasis , Proteína 2 Inhibidora de la Diferenciación/genética , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Linfocitos/inmunología , Masculino , Ratones , Regiones Promotoras Genéticas , Factor de Transcripción STAT5/metabolismo , Transcripción Genética
4.
Sensors (Basel) ; 24(4)2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38400457

RESUMEN

In the era of big data, millions and millions of data are generated every second by different types of devices. Training machine-learning models with these data has become increasingly common. However, the data used for training are often sensitive and may contain information such as medical, banking, or consumer records, for example. These data can cause problems in people's lives if they are leaked and also incur sanctions for companies that leak personal information for any reason. In this context, Federated Learning emerges as a solution to the privacy of personal data. However, even when only the gradients of the local models are shared with the central server, some attacks can reconstruct user data, allowing a malicious server to violate the FL principle, which is to ensure the privacy of local data. We propose a secure aggregation protocol for Decentralized Federated Learning, which does not require a central server to orchestrate the aggregation process. To achieve this, we combined a Multi-Secret-Sharing scheme with a Dining Cryptographers Network. We validate the proposed protocol in simulations using the MNIST handwritten digits dataset. This protocol achieves results comparable to Federated Learning with the FedAvg protocol while adding a layer of privacy to the models. Furthermore, it obtains a timing performance that does not significantly affect the total training time, unlike protocols that use Homomorphic Encryption.

5.
Radiographics ; 43(4): e220087, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36952256

RESUMEN

Gadoxetic acid is an MRI contrast agent that has specific applications in the study of hepatobiliary disease. After being distributed in the vascular and extravascular spaces during the dynamic phase, gadoxetic acid is progressively taken up by hepatocytes and excreted to the bile ducts during the hepatobiliary phase. The information derived from the enhancement characteristics during dynamic and hepatobiliary phases is particularly relevant in the detection and characterization of focal liver lesions and in the evaluation of the structure and function of the liver and biliary system. The use of new MRI sequences and advanced imaging techniques (eg, relaxometry, multiparametric imaging, and analysis of heterogeneity), the introduction of artificial intelligence, and the development of biomarkers and radiomic and radiogenomic tools based on gadoxetic acid-enhanced MRI findings will play an important role in the future in assessing liver function, chronic liver disease, and focal liver lesions; in studying biliary pathologic conditions; and in predicting treatment responses and prognosis. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.


Asunto(s)
Medios de Contraste , Enfermedades del Sistema Digestivo , Gadolinio DTPA , Imagen por Resonancia Magnética , Humanos , Inteligencia Artificial , Carcinoma Hepatocelular , Medios de Contraste/administración & dosificación , Gadolinio DTPA/administración & dosificación , Enfermedades de la Vesícula Biliar , Neoplasias Hepáticas , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Sensibilidad y Especificidad , Enfermedades del Sistema Digestivo/diagnóstico por imagen , Técnicas de Diagnóstico del Sistema Digestivo
6.
Aging Clin Exp Res ; 35(7): 1449-1457, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37202598

RESUMEN

BACKGROUND: Osteoarthritis is the most prevalent type of arthritis. Many approaches exist for characterising radiographic knee OA, including machine learning (ML). AIMS: To examine Kellgren and Lawrence (K&L) scores from ML and expert observation, minimum joint space and osteophyte in relation to pain and function. METHODS: Participants from the Hertfordshire Cohort Study, comprising individuals born in Hertfordshire from 1931 to 1939, were analysed. Radiographs were assessed by clinicians and ML (convolutional neural networks) for K&L scoring. Medial minimum joint space and osteophyte area were ascertained using the knee OA computer-aided diagnosis (KOACAD) program. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was administered. Receiver operating characteristic analysis was implemented for minimum joint space, osteophyte, and observer- and ML-derived K&L scores in relation to pain (WOMAC pain score > 0) and impaired function (WOMAC function score > 0). RESULTS: 359 participants (aged 71-80) were analysed. Among both sexes, discriminative capacity regarding pain and function was fairly high for observer-derived K&L scores [area under curve (AUC): 0.65 (95% CI 0.57, 0.72) to 0.70 (0.63, 0.77)]; results were similar among women for ML-derived K&L scores. Discriminative capacity was moderate among men for minimum joint space in relation to pain [0.60 (0.51, 0.67)] and function [0.62 (0.54, 0.69)]. AUC < 0.60 for other sex-specific associations. DISCUSSION: Observer-derived K&L scores had higher discriminative capacity regarding pain and function compared to minimum joint space and osteophyte. Among women, discriminative capacity was similar for observer- and ML-derived K&L scores. CONCLUSION: ML as an adjunct to expert observation for K&L scoring may be beneficial due to the efficiency and objectivity of ML.


Asunto(s)
Osteoartritis de la Rodilla , Osteofito , Masculino , Humanos , Femenino , Osteoartritis de la Rodilla/diagnóstico por imagen , Estudios de Cohortes , Osteofito/diagnóstico por imagen , Articulación de la Rodilla , Dolor , Índice de Severidad de la Enfermedad
7.
Eur J Neurol ; 28(10): 3360-3368, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33884707

RESUMEN

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.


Asunto(s)
COVID-19 , Enfermedades del Sistema Nervioso , Humanos , Enfermedades del Sistema Nervioso/epidemiología , Portugal/epidemiología , Estudios Retrospectivos , SARS-CoV-2
8.
J Environ Manage ; 294: 112937, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34119993

RESUMEN

Contamination of surrounding waters with antibiotics by aquaculture effluents can be problematic due to the possible increase of bacterial resistance, making it crucial the efficient treatment of those effluents before their release into the environment. In this work, the application of waste-based magnetic biochar/titanium dioxide (BC/TiO2) composite materials on the photodegradation of two antibiotics widely used in aquaculture (sulfadiazine (SDZ) and oxolinic acid (OXA)) was assessed. Four materials were synthesized: BCMag (magnetized BC), BCMag_TiO2 (BCMag functionalized with TiO2), BC_TiO2_MagIn and BC_TiO2_MagEx (BC functionalized with TiO2 and afterwards magnetized by in-situ and ex-situ approaches, respectively). SDZ half-life time (t1/2) noticeably decreased 3.9 and 3.4 times in presence of BCMag_TiO2 and BC_TiO2_MagEx, respectively. In the case of OXA, even though differences were not so substantial, the produced photocatalysts also allowed for a decrease in t1/2 (2.6 and 1.7 times, in presence of BCMag_TiO2 and BC_TiO2_MagEx, respectively). Overall, the here synthesized BC/TiO2 magnetic nanocomposites through a circular economy process are promising photocatalysts for a sustainable solar-driven removal of antibiotics from aquaculture effluents.


Asunto(s)
Antibacterianos , Nanocompuestos , Acuicultura , Catálisis , Carbón Orgánico , Luz Solar , Titanio
9.
Nature ; 514(7520): 98-101, 2014 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-25079320

RESUMEN

Haematopoiesis is a developmental cascade that generates all blood cell lineages in health and disease. This process relies on quiescent haematopoietic stem cells capable of differentiating, self renewing and expanding upon physiological demand. However, the mechanisms that regulate haematopoietic stem cell homeostasis and function remain largely unknown. Here we show that the neurotrophic factor receptor RET (rearranged during transfection) drives haematopoietic stem cell survival, expansion and function. We find that haematopoietic stem cells express RET and that its neurotrophic factor partners are produced in the haematopoietic stem cell environment. Ablation of Ret leads to impaired survival and reduced numbers of haematopoietic stem cells with normal differentiation potential, but loss of cell-autonomous stress response and reconstitution potential. Strikingly, RET signals provide haematopoietic stem cells with critical Bcl2 and Bcl2l1 surviving cues, downstream of p38 mitogen-activated protein (MAP) kinase and cyclic-AMP-response element binding protein (CREB) activation. Accordingly, enforced expression of RET downstream targets, Bcl2 or Bcl2l1, is sufficient to restore the activity of Ret null progenitors in vivo. Activation of RET results in improved haematopoietic stem cell survival, expansion and in vivo transplantation efficiency. Remarkably, human cord-blood progenitor expansion and transplantation is also improved by neurotrophic factors, opening the way for exploration of RET agonists in human haematopoietic stem cell transplantation. Our work shows that neurotrophic factors are novel components of the haematopoietic stem cell microenvironment, revealing that haematopoietic stem cells and neurons are regulated by similar signals.


Asunto(s)
Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Proteínas Proto-Oncogénicas c-ret/metabolismo , Animales , Supervivencia Celular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Activación Enzimática , Femenino , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-ret/deficiencia , Proteínas Proto-Oncogénicas c-ret/genética , Transducción de Señal , Nicho de Células Madre , Proteína bcl-X/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
10.
J Immunol ; 195(7): 3463-71, 2015 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-26297763

RESUMEN

Invariant NKT (iNKT) cell thymic development can lead to distinct committed effector lineages, namely NKT1, NKT2, and NKT17. However, following identification of IL-9-producing iNKT cells involved in mucosal inflammation, their development remains unaddressed. In this study, we report that although thymic iNKT cells from naive mice do not express IL-9, iNKT cell activation in the presence of TGF-ß and IL-4 induces IL-9 secretion in murine and human iNKT cells. Acquisition of IL-9 production was observed in different iNKT subsets defined by CD4, NK1.1, and neuropilin-1, indicating that distinct functional subpopulations are receptive to IL-9 polarization. Transcription factor expression kinetics suggest that regulatory mechanisms of IL-9 expression are shared by iNKT and CD4 T cells, with Irf4 and Batf deficiency deeply affecting IL-9 production. Importantly, adoptive transfer of an enriched IL-9(+) iNKT cell population leads to exacerbated allergic inflammation in the airways upon intranasal immunization with house dust mite, confirming the ability of IL-9-producing iNKT cells to mediate proinflammatory effects in vivo, as previously reported. Taken together, our data show that peripheral iNKT cells retain the capacity of shaping their function in response to environmental cues, namely TGF-ß and IL-4, adopting an IL-9-producing NKT cell phenotype able to mediate proinflammatory effects in vivo, namely granulocyte and mast cell recruitment to the lungs.


Asunto(s)
Interleucina-4/inmunología , Interleucina-9/biosíntesis , Células T Asesinas Naturales/inmunología , Neumonía/inmunología , Factor de Crecimiento Transformador beta/inmunología , Traslado Adoptivo , Animales , Antígenos Ly/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Antígenos CD4/metabolismo , Células Cultivadas , Granulocitos/inmunología , Humanos , Inflamación/inmunología , Factores Reguladores del Interferón/genética , Interleucina-9/metabolismo , Leucocitos Mononucleares/inmunología , Pulmón/inmunología , Pulmón/patología , Mastocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Subfamilia B de Receptores Similares a Lectina de Células NK/metabolismo , Células T Asesinas Naturales/trasplante , Neuropilina-1/metabolismo , Pyroglyphidae/inmunología , Timo/embriología , Timo/inmunología
11.
Proc Natl Acad Sci U S A ; 110(25): 10240-5, 2013 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-23733962

RESUMEN

Group 2 innate lymphoid cells (ILC2s; also called nuocytes, innate helper cells, or natural helper cells) provide protective immunity during helminth infection and play an important role in influenza-induced and allergic airway hyperreactivity. Whereas the transcription factor GATA binding protein 3 (Gata3) is important for the production of IL-5 and -13 by ILC2s in response to IL-33 or -25 stimulation, it is not known whether Gata3 is required for ILC2 development from hematopoietic stem cells. Here, we show that chimeric mice generated with Gata3-deficient fetal liver hematopoietic stem cells fail to develop systemically dispersed ILC2s. In these chimeric mice, in vivo administration of IL-33 or -25 fails to expand ILC2 numbers or to induce characteristic ILC2-dependent IL-5 or -13 production. Moreover, cell-intrinsic Gata3 expression is required for ILC2 development in vitro and in vivo. Using mutant and transgenic mice in which Gata3 gene copy number is altered, we show that ILC2 generation from common lymphoid progenitors, as well as ILC2 homeostasis and cytokine production, is regulated by Gata3 expression levels in a dose-dependent fashion. Collectively, these results identify Gata3 as a critical early regulator of ILC2 development, thereby extending the paradigm of Gata3-dependent control of type 2 immunity to include both innate and adaptive lymphocytes.


Asunto(s)
Factor de Transcripción GATA3/genética , Interleucina-13/genética , Interleucina-5/genética , Linfocitos/inmunología , Animales , Asma/genética , Asma/inmunología , Factor de Transcripción GATA3/inmunología , Dosificación de Gen/genética , Dosificación de Gen/inmunología , Homeostasis/inmunología , Inmunidad Innata/genética , Inmunidad Innata/inmunología , Inflamación/inducido químicamente , Inflamación/inmunología , Interleucina-13/inmunología , Interleucina-33 , Interleucina-5/inmunología , Interleucinas/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos
12.
Eur J Immunol ; 44(12): 3605-13, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25168352

RESUMEN

T helper (Th) cells are critical players in the modulation of immune response outcomes. Activation of Th cells gives rise to various subsets of effector cells that are controlled via specialised regulatory T cells or through self-regulation via production of IL-10. However, the environmental factors that regulate IL-10 production by Th cells remain poorly understood. Here, we show that the neurotrophic factor receptor rearranged during transfection (RET) downregulates IL-10 production by Th cells from C57BL/6 mice. We found that effector Th cells express RET and that RET's neurotrophic factor partners are mainly produced by LN stromal cells, allowing context-dependent Th-cell regulation. Despite being dispensable for Th-cell homeostasis, RET controls IL-10 production in Th2 cells: RET-deficient Th cells exhibited increased IL-10 production, while triggering of Th1/2 cells with neurotrophic factors, namely glial-derived neurotrophic factor and neurturin, decreased the expression of IL-10. In agreement, the important IL-10 transcription factor Maf was upregulated in RET-deficient Th2 cells and down-regulated upon RET signalling activation by glial-derived neurotrophic factor family ligands. Thus, our study uncovers neurotrophic factors as novel regulators of Th-cell function, revealing that Th cells and neurons can be regulated by similar signals in tissue-specific responses.


Asunto(s)
Interleucina-10/inmunología , Neurturina/inmunología , Proteínas Proto-Oncogénicas c-ret/inmunología , Transducción de Señal/inmunología , Células Th2/inmunología , Animales , Interleucina-10/genética , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Ratones , Ratones Noqueados , Neuroglía/citología , Neuroglía/inmunología , Neuronas/citología , Neuronas/inmunología , Neurturina/genética , Proteínas Proto-Oncogénicas c-ret/genética , Transducción de Señal/genética , Células del Estroma/citología , Células del Estroma/inmunología , Células TH1/citología , Células TH1/inmunología , Células Th2/citología
13.
Aust Fam Physician ; 43(1): 36-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24563892

RESUMEN

A case study A previously healthy woman, aged 37 years, presented with a 4-week history of pruritic periungual rash and subungual pain. Physical examination revealed scaly, fissured, erythematous plaques around her fingernails (Figure 1). Underneath the acrylic artificial nails that she had been wearing for 6 weeks, onycholysis and nail bed hyperkeratosis were evident. Oral terbinafine and amorolfine nail polish were prescribed by the general practitioner but had no clinical benefit.


Asunto(s)
Acrilatos/efectos adversos , Dermatitis Alérgica por Contacto/diagnóstico , Exantema/etiología , Uñas , Adulto , Antiinflamatorios/uso terapéutico , Betametasona/análogos & derivados , Betametasona/uso terapéutico , Cosméticos/efectos adversos , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/etiología , Diagnóstico Diferencial , Femenino , Humanos , Onicomicosis/diagnóstico , Pruebas del Parche , Psoriasis/diagnóstico
14.
Environ Toxicol Pharmacol ; 106: 104372, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38244879

RESUMEN

Interaction of nanoplastics (NPls) with other environmental contaminants could affect their uptake by the organisms and their toxicity. Thus, the present study aims to investigate the polystyrene NPls (44 nm) interaction with the antidepressant amitriptyline (AMI) and its toxicity to Danio rerio embryos. A similar toxicological profile for NPls + AMI exposure was found for most of the evaluated endpoints, comparing with AMI single exposure, showing that the presence of NPls did not modulate the AMI toxicity. However, the behavioral assessment showed a different pattern with hypoactivity for the NPls + AMI exposure (NPls - hyperactivity; AMI - no effect). Interaction effects between NPls and AMI were also found in the protein contents (antagonism) and in the total glutathione content (synergism). This study highlights the complexity and unpredictability of NPls interaction with pharmaceuticals, important for an accurate environmental risk assessment and for the developing of effective strategies and interventions against plastic pollution.


Asunto(s)
Amitriptilina , Contaminantes Químicos del Agua , Animales , Amitriptilina/toxicidad , Pez Cebra/metabolismo , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismo , Poliestirenos/toxicidad
15.
Eur J Pharm Biopharm ; 202: 114390, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38950716

RESUMEN

The current pharmacological management of androgenetic alopecia is inconvenient and requires a discipline that patients find difficult to follow. This reduces compliance with treatment and satisfaction with results. It is important to propose treatment regimens that increase patient compliance and reduce adverse effects. This work describes transdermal delivery of minoxidil partially encapsulated in ß-cyclodextrin and assisted by photoacoustic waves. Photoacoustic waves transiently increase the permeability of the skin and allow for the delivery of encapsulated minoxidil. A minoxidil gel formulation was developed and the transdermal delivery was studied in vitro in the presence and absence of photoacoustic waves. A 5-min stimulus with photoacoustic waves generated by light-to-pressure transducers increases minoxidil transdermal delivery flux by approximately 3-fold. The flux of a 1% minoxidil formulation promoted by photoacoustic waves is similar to the passive flux of a 2% minoxidil commercial formulation. Release of minoxidil from ß-cyclodextrin increases dermal exposure without increasing peak systemic exposure. This promotes hair growth with fewer treatments and reduced adverse effects. In vivo studies using encapsulated minoxidil and photoacoustic waves yielded 86% hair coat recovery (vs. 29% in the control group) and no changes in the blood pressure.


Asunto(s)
Administración Cutánea , Alopecia , Cabello , Minoxidil , Minoxidil/administración & dosificación , Minoxidil/farmacocinética , Animales , Alopecia/tratamiento farmacológico , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Absorción Cutánea/efectos de los fármacos , beta-Ciclodextrinas/química , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Piel/efectos de los fármacos , Ciclodextrinas/química , Ciclodextrinas/administración & dosificación , Masculino , Técnicas Fotoacústicas/métodos , Humanos , Geles
16.
Gut Microbes ; 16(1): 2392874, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39163515

RESUMEN

Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation. Allobaculum spp. expanded in binge drinking mice, and administration of Allobaculum fili was sufficient to enhance colitis in non-drinking mice. Our study provides a model to study binge drinking-microbiota interactions and their effects on host disease and reinforces the pathogenic function of Allobaculum spp. as colitogenic bacteria. Our findings illustrate how chronic binge drinking-induced alterations of the microbiome may affect susceptibility to IBD onset or flares.


Asunto(s)
Consumo Excesivo de Bebidas Alcohólicas , Colitis , Colon , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Animales , Consumo Excesivo de Bebidas Alcohólicas/complicaciones , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Colitis/microbiología , Colitis/inducido químicamente , Colon/microbiología , Colon/patología , Modelos Animales de Enfermedad , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Etanol/efectos adversos , Susceptibilidad a Enfermedades , Masculino , Vida Libre de Gérmenes , Inflamación/microbiología , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/patología
17.
Pathogens ; 13(6)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38921753

RESUMEN

Visceral leishmaniasis is a disease caused by protozoa of the species Leishmania (Leishmania) infantum (syn = Leishmania chagasi) and Leishmania (Leishmania) donovani, which are transmitted by hematophagous insects of the genera Lutzomyia and Phlebotomus. The domestic dog (Canis familiaris) is considered the main urban reservoir of the parasite due to the high parasite load on its skin, serving as a source of infection for sandfly vectors and, consequently, perpetuating the disease in the urban environment. Some factors are considered important in the perpetuation and spread of canine visceral leishmaniasis (CVL) in urban areas, such as stray dogs, with their errant behavior, and houses that have backyards with trees, shade, and organic materials, creating an attractive environment for sandfly vectors. CVL is found in approximately 50 countries, with the number of infected dogs reaching millions. However, due to the difficulty of controlling and diagnosing the disease, the number of infected animals could be even greater. In the four continents endemic for CVL, there are reports of disease expansion in endemic countries such as Brazil, Italy, Morocco, and Tunisia, as well as in areas where CVL is not endemic, for example, Uruguay. Socio-environmental factors, such as migration, drought, deforestation, and global warming, have been pointed out as reasons for the expansion into areas where it had been absent. Thus, the objective of this review is to address (i) the distribution of CVL in endemic areas, (ii) the role of the dog in the visceral leishmaniasis epidemiology and the factors that influence dog infection and the spread of the disease, and (iii) the challenges faced in the control of CVL.

18.
Vaccines (Basel) ; 12(3)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38543905

RESUMEN

The development of prophylactic vaccines is important in preventing and controlling diseases such as visceral leishmaniasis (VL), in addition to being an economic measure for public health. Despite the efforts to develop a vaccine against human VL caused by Leishmania infantum, none is available, and the focus has shifted to developing vaccines against canine visceral leishmaniasis (CVL). Currently, commercially available vaccines are targeted at CVL but are not effective. Different strategies have been applied in developing and improving vaccines, such as using chimeric proteins to expand vaccine coverage. The search for patents can be a way of tracking vaccines that have the potential to be marketed. In this context, the present work presents a summary of immunological aspects relevant to VL vaccine development with a focus on the composition of chimeric protein vaccines for CVL deposited in patent banks as an important approach for biotechnological development. The resulting data could facilitate the screening and selection of antigens to compose vaccine candidates with high performance against VL.

19.
Molecules ; 18(8): 9397-419, 2013 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-23924993

RESUMEN

In this study, a series of twenty-two ring-substituted 2-hydroxynaphthalene-1­carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium marinum, M. kasasii, M. smegmatis. and M. avium paratuberculosis. The compounds were also tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 2-Hydroxy-N-phenylnaphthalene-1-carboxanilide and 2-hydroxy-N-(3-trifluoromethylphenyl)naphthalene-1-carboxamide (IC50 = 29 µmol/L) were the most active PET inhibitors. Some of tested compounds showed the antibacterial and antimycobacterial activity against the tested strains comparable or higher than the standards ampicillin or isoniazid. Thus, for example, 2-hydroxy-N-(3-nitrophenyl)naphthalene-1-carboxamide showed MIC = 26.0 µmol/L against methicillin-resistant S. aureus and MIC = 51.9 µmol/L against M. marinum, or 2-hydroxy-N-phenylnaphthalene-1-carboxamide demonstrated MIC = 15.2 µmol/L against M. kansasii. The structure-activity relationships for all compounds are discussed.


Asunto(s)
Antibacterianos/farmacología , Herbicidas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Naftoles/farmacología , Antibacterianos/química , Cloroplastos/efectos de los fármacos , Cloroplastos/metabolismo , Transporte de Electrón , Herbicidas/química , Pruebas de Sensibilidad Microbiana , Mycobacterium/efectos de los fármacos , Naftoles/química , Fotosíntesis/efectos de los fármacos , Spinacia oleracea/efectos de los fármacos , Spinacia oleracea/metabolismo , Relación Estructura-Actividad
20.
J Hazard Mater ; 443(Pt B): 130258, 2023 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-36351346

RESUMEN

Pharmaceuticals are able to evade conventional wastewater treatments and therefore, are recurrently found in the environment with proven potential to cause harm to human and wildlife. Adsorption onto activated carbon (AC) is a promising complement. However, AC production from non-renewable resources and its difficult after-use recuperation are prohibitive. Hence, a waste-based magnetic activated carbon (MAC) was produced from paper mill sludge, via an ex-situ synthesis, for the adsorptive removal of carbamazepine (CBZ), sulfamethoxazole (SMX) and ibuprofen (IBU) from ultrapure water and wastewater. The MAC was obtained through the promotion of electrostatic interactions between magnetic and activated carbon particles in a water suspension at controlled pH between the points of zero charge of both surfaces. The optimized condition (MACX3) presented remarkable properties regarding specific surface area (SBET=795 m2 g-1) and saturation magnetization (MS=19 emu g-1). Kinetic and equilibrium adsorption studies were performed under batch conditions. Adsorption equilibrium was reached in up to 30 min for all pharmaceuticals in both matrices, proving the low dependence on the adsorbate and the broad applicability of MACX3 in pharmaceutical adsorption. Regarding equilibrium experiments, high Langmuir maximum adsorption capacities (qm) were achieved in ultrapure water (up to 711 ± 40 µmol g-1). Equilibrium studies in wastewater revealed a decay in qm when compared to ultrapure water: 28% for CBZ (468 ± 20 µmol g-1 (111 ± 5 mg g-1)), 78% for SMX (145 ± 10 µmol g-1 (37 ± 3 mg g-1)) and 62% for IBU (273 ± 8 µmol g-1 (56 ± 2 mg g-1)), attributed to the wastewater pH, which dictates the speciation of the pharmaceuticals and controls electrostatic interactions between pharmaceuticals and MAC, and to competition effects by organic matter. It was demonstrated the promising applicability of a waste-based ex-situ MAC, rapidly retrievable from water, as an alternative tertiary wastewater treatment for pharmaceuticals removal.


Asunto(s)
Carbón Orgánico , Aguas Residuales , Humanos , Adsorción , Sulfametoxazol , Carbamazepina , Agua , Ibuprofeno , Preparaciones Farmacéuticas , Fenómenos Magnéticos
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