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1.
J Neuroinflammation ; 21(1): 219, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245706

RESUMEN

BACKGROUND: Depression is a chronic psychiatric disease of multifactorial etiology, and its pathophysiology is not fully understood. Stress and other chronic inflammatory pathologies are shared risk factors for psychiatric diseases, and comorbidities are features of major depression. Epidemiological evidence suggests that periodontitis, as a source of low-grade chronic systemic inflammation, may be associated with depression, but the underlying mechanisms are not well understood. METHODS: Periodontitis (P) was induced in Wistar: Han rats through oral gavage with the pathogenic bacteria Porphyromonas gingivalis and Fusobacterium nucleatum for 12 weeks, followed by 3 weeks of chronic mild stress (CMS) to induce depressive-like behavior. The following four groups were established (n = 12 rats/group): periodontitis and CMS (P + CMS+), periodontitis without CMS, CMS without periodontitis, and control. The morphology and inflammatory phenotype of microglia in the frontal cortex (FC) were studied using immunofluorescence and bioinformatics tools. The endocannabinoid (EC) signaling and proteins related to synaptic plasticity were analyzed in FC samples using biochemical and immunohistochemical techniques. RESULTS: Ultrastructural and fractal analyses of FC revealed a significant increase in the complexity and heterogeneity of Iba1 + parenchymal microglia in the combined experimental model (P + CMS+) and increased expression of the proinflammatory marker inducible nitric oxide synthase (iNOS), while there were no changes in the expression of cannabinoid receptor 2 (CB2). In the FC protein extracts of the P + CMS + animals, there was a decrease in the levels of the EC metabolic enzymes N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), and monoacylglycerol lipase (MAGL) compared to those in the controls, which extended to protein expression in neurons and in FC extracts of cannabinoid receptor 1 (CB1) and to the intracellular signaling molecules phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2). The protein levels of brain-derived neurotrophic factor (BDNF) and synaptophysin were also lower in P + CMS + animals than in controls. CONCLUSIONS: The combined effects on microglial morphology and inflammatory phenotype, the EC signaling, and proteins related to synaptic plasticity in P + CMS + animals may represent relevant mechanisms explaining the association between periodontitis and depression. These findings highlight potential therapeutic targets that warrant further investigation.


Asunto(s)
Depresión , Endocannabinoides , Microglía , Periodontitis , Ratas Wistar , Transducción de Señal , Animales , Ratas , Endocannabinoides/metabolismo , Microglía/metabolismo , Microglía/patología , Periodontitis/patología , Periodontitis/metabolismo , Transducción de Señal/fisiología , Depresión/metabolismo , Depresión/patología , Masculino , Modelos Animales de Enfermedad , Fenotipo , Inflamación/metabolismo , Inflamación/patología
2.
Ciênc. Saúde Colet. (Impr.) ; 29(8): e06042024, ago. 2024.
Artículo en Portugués | LILACS-Express | LILACS | ID: biblio-1569055

RESUMEN

Resumo Objetivou-se analisar a percepção de estudantes e egressos sobre a utilização da Aprendizagem Baseada em Problemas (ABP) na formação do enfermeiro. Trata-se de um estudo qualitativo que utiliza a modalidade compreensiva e interpretativa proposta pela Hermenêutica-Dialética. Realizaram-se quatro grupos focais com a participação de 17 estudantes e 16 egressos de uma instituição de ensino superior que aplica a ABP na formação de enfermeiros. A análise dos resultados permitiu a definição de cinco categorias temáticas: dificuldade de adaptação em relação ao método; conquista de autonomia sobre o próprio aprendizado; incentivo ao desenvolvimento do raciocínio clínico; aprimoramento da comunicação e das relações interpessoais e integração entre teoria e prática. Evidencia-se que a utilização da ABP favorece a aproximação com as proposições das diretrizes curriculares para a formação do enfermeiro por meio do desenvolvimento de habilidades e competências como autonomia, comunicação, relações interpessoais e raciocínio clínico mediante práticas integrais e contextualizadas. Entretanto, os estudantes enfrentam dificuldades com as mudanças observadas ao serem inseridos nela ABP, as quais são superadas no decorrer do processo de implementação.


Abstract This study aimed to analyze students' and graduates' perceptions regarding the use of Problem-Based Learning (PBL) in nurse education. This is a qualitative study that employs the comprehensive and interpretative approach proposed by Dialectical Hermeneutics. Four focus groups were conducted with the participation of 17 students and 16 graduates from a higher education institution that implements PBL in nurse education. The analysis of results allowed for the identification of five thematic categories: difficulty in adapting to the method; attainment of autonomy in one's own learning; encouragement of clinical reasoning development; enhancement of communication and interpersonal relationships; and integration between theory and practice. It is evident that the use of PBL promotes alignment with the propositions of curriculum guidelines for nurse education by fostering the development of skills and competencies such as autonomy, communication, interpersonal relationships, and clinical reasoning through comprehensive and contextualized practices. However, students encounter challenges with the changes observed when introduced to PBL, which are overcome during the implementation process.

3.
Cien Saude Colet ; 29(8): e06042024, 2024 Aug.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-39140543

RESUMEN

This study aimed to analyze students' and graduates' perceptions regarding the use of Problem-Based Learning (PBL) in nurse education. This is a qualitative study that employs the comprehensive and interpretative approach proposed by Dialectical Hermeneutics. Four focus groups were conducted with the participation of 17 students and 16 graduates from a higher education institution that implements PBL in nurse education. The analysis of results allowed for the identification of five thematic categories: difficulty in adapting to the method; attainment of autonomy in one's own learning; encouragement of clinical reasoning development; enhancement of communication and interpersonal relationships; and integration between theory and practice. It is evident that the use of PBL promotes alignment with the propositions of curriculum guidelines for nurse education by fostering the development of skills and competencies such as autonomy, communication, interpersonal relationships, and clinical reasoning through comprehensive and contextualized practices. However, students encounter challenges with the changes observed when introduced to PBL, which are overcome during the implementation process.


Objetivou-se analisar a percepção de estudantes e egressos sobre a utilização da Aprendizagem Baseada em Problemas (ABP) na formação do enfermeiro. Trata-se de um estudo qualitativo que utiliza a modalidade compreensiva e interpretativa proposta pela Hermenêutica-Dialética. Realizaram-se quatro grupos focais com a participação de 17 estudantes e 16 egressos de uma instituição de ensino superior que aplica a ABP na formação de enfermeiros. A análise dos resultados permitiu a definição de cinco categorias temáticas: dificuldade de adaptação em relação ao método; conquista de autonomia sobre o próprio aprendizado; incentivo ao desenvolvimento do raciocínio clínico; aprimoramento da comunicação e das relações interpessoais e integração entre teoria e prática. Evidencia-se que a utilização da ABP favorece a aproximação com as proposições das diretrizes curriculares para a formação do enfermeiro por meio do desenvolvimento de habilidades e competências como autonomia, comunicação, relações interpessoais e raciocínio clínico mediante práticas integrais e contextualizadas. Entretanto, os estudantes enfrentam dificuldades com as mudanças observadas ao serem inseridos nela ABP, as quais são superadas no decorrer do processo de implementação.


Asunto(s)
Bachillerato en Enfermería , Grupos Focales , Aprendizaje Basado en Problemas , Estudiantes de Enfermería , Humanos , Aprendizaje Basado en Problemas/métodos , Estudiantes de Enfermería/psicología , Bachillerato en Enfermería/métodos , Masculino , Femenino , Curriculum , Adulto Joven , Comunicación , Adulto , Relaciones Interpersonales , Investigación Cualitativa , Razonamiento Clínico , Competencia Clínica , Actitud del Personal de Salud
4.
Mol Oncol ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090849

RESUMEN

Glioblastoma (GB) is the most common and fatal type of primary malignant brain tumor for which effective therapeutics are still lacking. GB stem cells, with tumor-initiating and self-renewal capacity, are mostly responsible for GB malignancy, representing a crucial target for therapies. The TP73 gene, which is highly expressed in GB, gives rise to the TAp73 isoform, a pleiotropic protein that regulates neural stem cell biology; however, its role in cancer has been highly controversial. We inactivated TP73 in human GB stem cells and revealed that TAp73 is required for their stemness potential, acting as a regulator of the transcriptional stemness signatures, highlighting TAp73 as a possible therapeutic target. As proof of concept, we identified a novel natural compound with TAp73-inhibitory capacity, which was highly effective against GB stem cells. The treatment reduced GB stem cell-invasion capacity and stem features, at least in part by TAp73 repression. Our data are consistent with a novel paradigm in which hijacking of p73-regulated neurodevelopmental programs, including neural stemness, might sustain tumor progression, pointing out TAp73 as a therapeutic strategy for GB.

5.
Nucleic Acids Res ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39149904

RESUMEN

The programmed ribosomal frameshift (PRF) region is found in the RNA genome of all coronaviruses and shifts the ribosome reading frame through formation of a three-stem pseudoknot structure, allowing the translation of essential viral proteins. Using NMR spectroscopy, comparative sequence analyses and functional assays we show that, in the absence of the ribosome, a 123-nucleotide sequence encompassing the PRF element of SARS-CoV-2 adopts a well-defined two-stem loop structure that is conserved in all SARS-like coronaviruses. In this conformation, the attenuator hairpin and slippery site nucleotides are exposed in the first stem-loop and two pseudoknot stems are present in the second stem-loop, separated by an 8-nucleotide bulge. Formation of the third pseudoknot stem depends on pairing between bulge nucleotides and base-paired nucleotides of the upstream stem-loop, as shown by a PRF construct where residues of the upstream stem were removed, which formed the pseudoknot structure and had increased frameshifting activity in a dual-luciferase assay. The base-pair switch driving PRF pseudoknot folding was found to be conserved in several human non-SARS coronaviruses. The collective results suggest that the frameshifting pseudoknot structure of these viruses only forms transiently in the presence of the translating ribosome. These findings clarify the frameshifting mechanism in coronaviruses and can have a beneficial impact on antiviral drug discovery.

6.
J Histochem Cytochem ; : 221554241272341, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39180315

RESUMEN

Primary malignancies of the central nervous system account for 2% of all cancers in adults and almost 15% in children under 15 years of age. The prognosis of brain anaplastic cancers and glioblastomas remains extremely poor, with devastating survival expectative, and new molecular markers and therapeutic targets are essential. Epigenetic changes constitute an extensive field for the development of new diagnostic and therapeutic strategies. Histone acetyl transferase-1 (HAT1) has merged as a potential prognostic marker and therapy target for different malignancies. Data repository analysis showed HAT1 mRNA overexpression in gliomas and has been described its alternative splicing in glioblastomas. Using immunohistochemical and aptahistochemical methods, we analyzed the expression of HAT1 in meningiomas, oligodendrogliomas, and astroglial cancers. We observed that HAT1 overexpression is associated with the most aggressive tumor types and the worse prognosis, as well as with a higher probability of early relapse in meningiomas. Its cytosolic localization correlates with tumor progression and prognosis. Aptamers, synthetic oligonucleotides capable to bind and inhibit a wide variety of targets, are considered as promising diagnostic and therapeutic tools. Aptahistochemistry using the aptamer apHAT610 offered superior results in comparison with the antibody used, as a good example of the potential of aptamers as diagnostic tools for histopathology.

7.
Environ Sci Pollut Res Int ; 31(39): 51687-51701, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39120814

RESUMEN

Alterations in seawater chemistry posed by acidification may lead to immunological and antioxidant defence impairment in sea urchins, with differences among local populations. Here, we analyzed the effects of reduced pH on Paracentrotus lividus, with a multibiomarker approach, and the possible intraspecific variations in sea urchin responses. Two groups of animals with different ecological histories (i.e., the pattern of environmental characteristics and pressures experienced throughout the organism's lifetime) were maintained at ambient pH and pH reduced of 0.4 units for 8 months. Changes in gonadosomatic index (GSI), immunological, and oxidative stress biomarkers were assessed in coelomic fluid, gonads, and digestive tract. Animals maintained at reduced pH showed limited impact of seawater acidification compared to the ambient pH condition. However, sea urchins from the two sites were differently influenced by the seawater pH (as shown by multivariate analyses). GSI and immunological and antioxidant status were differentially modulated between the two sexes, with generally higher values in females, but differences between sexes in relation to the pH of exposure were limited. Overall, our findings highlight that the impact of environmental stressors may differ in sea urchins from different locations. This has implications for the maintenance of P. lividus wild populations under future global change scenarios.


Asunto(s)
Paracentrotus , Agua de Mar , Animales , Agua de Mar/química , Concentración de Iones de Hidrógeno , Estrés Oxidativo , Erizos de Mar , Femenino , Masculino , Acidificación de los Océanos
8.
Nutrients ; 16(16)2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39203857

RESUMEN

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2256 documents, leading to the selection of 15 clinical trials for synthesis. Here, we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.


Asunto(s)
Antioxidantes , Curcumina , Envejecimiento Saludable , Anciano , Humanos , Envejecimiento/efectos de los fármacos , Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Cognición/efectos de los fármacos , Curcumina/administración & dosificación , Suplementos Dietéticos , Estrés Oxidativo/efectos de los fármacos , Calidad de Vida
9.
Pathogens ; 13(7)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39057777

RESUMEN

Candida auris is an emerging, multidrug-resistant yeast that causes systemic infections, mainly in hospitalized or immunosuppressed patients. This pathogen has a high mortality and morbidity rate. This study aims to evaluate the antifungal potential of micafungin (MICA) encapsulated in a nanoemulsion (NEM) against four clades of C. auris and other non-C. auris species. The antifungal potential of MICA and NEM was evaluated by determining mature biofilm inhibition (0.78-50 µg/mL). The antifungal activities of MICA and NEM (5.92 mg/Kg) were evaluated using an in vivo model of Galleria mellonella. The results showed that NEM intensified the antibiofilm action of MICA, especially in 48 h mature biofilms. In vivo results displayed a higher effectiveness of NEM against all clades of C. auris tested, inhibiting the fungal load in the hemolymph and tissues of G. mellonella with a difference of 3 log10. In addition, C. auris infection caused granulomas surrounded by hemocytes, mainly at the lower and upper ends. Conversely, C. albicans developed pseudohyphae, biofilms, filaments, and chlamydospores. In conclusion, encapsulation of MICA in a nanoemulsion enhances its antifungal activity against mature biofilms of C. auris. This strategy may be considered a therapeutic approach for the control of infections and the dissemination of this new global health threat.

10.
J Phys Chem B ; 128(30): 7407-7426, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39024507

RESUMEN

Microbial pump rhodopsins are highly versatile light-driven membrane proteins that couple protein conformational dynamics with ion translocation across the cell membranes. Understanding how microbial pump rhodopsins use specific amino acid residues at key functional sites to control ion selectivity and ion pumping direction is of general interest for membrane transporters, and could guide site-directed mutagenesis for optogenetics applications. To enable direct comparisons between proteins with different sequences we implement, for the first time, a unique numbering scheme for the microbial pump rhodopsin residues, NS-mrho. We use NS-mrho to show that distinct microbial pump rhodopsins typically have hydrogen-bond networks that are less conserved than anticipated from the amino acid residue conservation, whereas their hydrophobic interaction networks are largely conserved. To illustrate the role of the hydrogen-bond networks as structural elements that determine the functionality of microbial pump rhodopsins, we performed experiments, atomic-level simulations, and hydrogen bond network analyses on GR, the outward proton pump from Gloeobacter violaceus, and KR2, the outward sodium pump from Krokinobacter eikastus. The experiments indicate that multiple mutations that recover KR2 amino acid residues in GR not only fail to convert it into a sodium pump, but completely inactivate GR by abolishing photoisomerization of the retinal chromophore. This observation could be attributed to the drastically altered hydrogen-bond interaction network identified with simulations and network analyses. Taken together, our findings suggest that functional specificity could be encoded in the collective hydrogen-bond network of microbial pump rhodopsins.


Asunto(s)
Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Rodopsinas Microbianas , Rodopsinas Microbianas/química , Rodopsinas Microbianas/metabolismo , Rodopsinas Microbianas/genética , Simulación de Dinámica Molecular , Flavobacteriaceae/metabolismo , Flavobacteriaceae/química , Bombas de Protones/metabolismo , Bombas de Protones/química , Cianobacterias/metabolismo
12.
Respir Med ; 231: 107717, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38908411

RESUMEN

INTRODUCTION: Enhancing lung function can significantly improve daily life functionality for children with cerebral palsy, leading to increased interest in respiratory physiotherapy training devices in clinical practice. This study aims to evaluate the efficacy of devices (inspiratory muscle training and feedback devices) for improving pulmonary function through various respiratory parameters. METHODS: A systematic review with meta-analysis of randomized clinical trials was conducted in seven databases up until May 2023. The included studies focused on training inspiratory muscle function using specific devices (inspiratory muscle training and feedback devices) in children with cerebral palsy. The main outcomes were maximum expiratory pressure and maximum inspiratory pressure. Secondary outcomes included forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and the Tiffenau index. The effects of respiratory treatment were calculated through the estimation of the effect size and its 95% confidence intervals. The risk of bias in the included studies was assessed using the Cochrane Collaboration's tool for assessing the risk of bias (RoB2). RESULTS: Nine studies were included in the systematic review with meta-analysis, involving a total of 321 children aged between 6 and 18 years after secondary analyses were conducted. Feedback devices were found to be more effective in improving maximum expiratory pressure (effect size -0.604; confidence interval -1.368 to 0.161), peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity. Inspiratory muscle training devices yielded better effectiveness in improving maximum inspiratory pressure (effect size -0.500; confidence interval -1.259 to 0.259), the Tiffeneau index, and quality of life. CONCLUSION: Both devices showed potential in improving pulmonary function in children with cerebral palsy. Further high-quality clinical trials are needed to determine the optimal dosage and the most beneficial device type for each pulmonary function parameter.


Asunto(s)
Ejercicios Respiratorios , Parálisis Cerebral , Ensayos Clínicos Controlados Aleatorios como Asunto , Músculos Respiratorios , Humanos , Parálisis Cerebral/rehabilitación , Parálisis Cerebral/fisiopatología , Niño , Adolescente , Músculos Respiratorios/fisiopatología , Ejercicios Respiratorios/métodos , Pruebas de Función Respiratoria , Volumen Espiratorio Forzado , Femenino , Capacidad Vital , Masculino , Resultado del Tratamiento , Pulmón/fisiopatología , Presiones Respiratorias Máximas , Terapia Respiratoria/métodos
13.
Sci Adv ; 10(21): eadj1539, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38781331

RESUMEN

Microbial associations and interactions drive and regulate nutrient fluxes in the ocean. However, physical contact between cells of marine cyanobacteria has not been studied thus far. Here, we show a mechanism of direct interaction between the marine cyanobacteria Prochlorococcus and Synechococcus, the intercellular membrane nanotubes. We present evidence of inter- and intra-genus exchange of cytoplasmic material between neighboring and distant cells of cyanobacteria mediated by nanotubes. We visualized and measured these structures in xenic and axenic cultures and in natural samples. We show that nanotubes are produced between living cells, suggesting that this is a relevant system of exchange material in vivo. The discovery of nanotubes acting as exchange bridges in the most abundant photosynthetic organisms in the ocean may have important implications for their interactions with other organisms and their population dynamics.


Asunto(s)
Nanotubos , Prochlorococcus , Synechococcus , Synechococcus/metabolismo , Nanotubos/química , Prochlorococcus/metabolismo , Cianobacterias/metabolismo , Organismos Acuáticos , Agua de Mar/microbiología
14.
Vet Sci ; 11(5)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38787182

RESUMEN

The increasing urbanization of ecosystems has had a significant impact on wildlife over the last few years. Species that find an unlimited supply of food and shelter in urban areas have thrived under human presence. Wild birds have been identified as amplifying hosts and reservoirs of Campylobacter worldwide, but the information about its transmission and epidemiology is still limited. This study assessed the prevalence of Campylobacter in 137 urban birds admitted at a wildlife rescue center, with 18.8% of individuals showing positive. C. jejuni was the most frequent species (82.6%), followed by C. coli and C. lari (4.3% each). The order Passeriformes (33.3%) showed significant higher presence of Campylobacter when compared to orders Columbiformes (0%) and Ciconiiformes (17.6%), as well as in samples collected during the summer season (31.9%), from omnivorous species (36.8%) and young individuals (26.8%). Globally, Campylobacter displayed a remarkable resistance to ciprofloxacin (70.6%), tetracycline (64.7%), and nalidixic acid (52.9%). In contrast, resistance to streptomycin was low (5.8%), and all the isolates showed susceptibility to erythromycin and gentamycin. The results underline the importance of urban birds as reservoirs of thermophilic antimicrobial-resistant Campylobacter and contribute to enhancing the knowledge of its distribution in urban and peri-urban ecosystems.

15.
Diagnostics (Basel) ; 14(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38611634

RESUMEN

Nasopharyngeal carcinoma is one of the most common malignant tumors in the head and neck region. The carcinogenesis is a complex process stimulated by many factors. Although the etiological factors and pathogenic mechanisms are not elucidated, the genetic susceptibility, environmental factors, and association with latent infection with Epstein-Barr Virus play an important role. The aim of this study was to present the main clinical and epidemiological data, as well as the morphological aspects and the immunohistochemical profile, of patients with nasopharyngeal carcinoma diagnosed in western Romania. The study was retrospective and included 36 nasopharyngeal carcinomas. The histopathological diagnosis was completed using immunohistochemical reactions for the following antibodies: p63, p53 and p16 protein, cytokeratins (CK) AE1/AE3, CK5, CK7, CK20 and 34ßE12, epithelial membrane antigen (EMA), Epstein-Barr virus (EBV), leukocyte common antigen (LCA), CD20, CD4, CD8, CD68, CD117, and CD1a. The squamous malignant component of nasopharyngeal carcinoma presented with positivity for cytokeratins AE1/AE3, CK5, 34ßE12, and p63. Undifferentiated nasopharyngeal carcinoma was positive for EMA in 67% of cases, and 28% of cases showed an immunoreaction for CD117 in the malignant epithelial component. Also, the p53 protein was positive in all the cases. One case of undifferentiated nasopharyngeal carcinoma was p16-positive, and two cases were positive for EBV. A peri- and intratumor cellular infiltrate rich in lymphocytes, with a predominance of CD20-positive B lymphocytes, interspersed with T lymphocytes, was observed. The T cells were CD4- and CD8-positive, predominantly intratumoral, and the CD4:CD8 ratio was 1:1 for 75% of the undifferentiated subtype and 89% for differentiated non-keratinized squamous cell carcinoma. All subtypes of nasopharyngeal carcinoma presented with an inflammatory infiltrate with numerous plasma cells, eosinophils, and dendritic cells, presenting as antigen CD1a- and CD68-positive, as well as in CD117-positive mast cells.

17.
Med Intensiva (Engl Ed) ; 48(7): 377-385, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38582715

RESUMEN

OBJECTIVE: To analyze the presence of frailty in survivors of severe COVID-19 admitted in the Intensive Care Unit (ICU) and followed six months after discharge. DESIGN: An observational, prospective and multicenter, nation-wide study. SETTING: Eight adult ICU across eight academic acute care hospitals in Mexico. PATIENTS: All consecutive adult COVID-19 patients admitted in the ICU with acute respiratory failure between March 8, 2020 to February 28, 2021 were included. Frailty was defined according to the FRAIL scale, and was obtained at ICU admission and 6-month after hospital discharge. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: The primary endpoint was the frailty status 6-months after discharge. A regression model was used to evaluate the predictors during ICU stay associated with frailty. RESULTS: 196 ICU survivors were evaluated for basal frailty at ICU admission and were included in this analysis. After 6-months from discharge, 164 patients were evaluated for frailty: 40 patients (20.4%) were classified as non-frail, 67 patients (34.2%) as pre-frail and 57 patients (29.1%) as frail. After adjustment, the need of invasive mechanical ventilation was the only factor independently associated with frailty at 6 month follow-up (Odds Ratio [OR] 3.70, 95% confidence interval 1.40-9.81, P = .008). CONCLUSIONS: Deterioration of frailty was reported frequently among ICU survivors with severe COVID-19 at 6-months. The need of invasive mechanical ventilation in ICU survivors was the only predictor independently associated with frailty.


Asunto(s)
COVID-19 , Fragilidad , Unidades de Cuidados Intensivos , Respiración Artificial , Sobrevivientes , Humanos , Fragilidad/epidemiología , COVID-19/terapia , COVID-19/complicaciones , COVID-19/epidemiología , México/epidemiología , Estudios Prospectivos , Masculino , Femenino , Unidades de Cuidados Intensivos/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Sobrevivientes/estadística & datos numéricos , Respiración Artificial/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Estudios de Seguimiento
18.
Cytotherapy ; 26(6): 632-640, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38556960

RESUMEN

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.


Asunto(s)
Displasia Broncopulmonar , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Cordón Umbilical , Humanos , Displasia Broncopulmonar/terapia , Femenino , Trasplante de Células Madre Mesenquimatosas/métodos , Masculino , Células Madre Mesenquimatosas/citología , Recién Nacido , Cordón Umbilical/citología , Estudios de Seguimiento , Administración Intravenosa , Edad Gestacional , Recien Nacido Prematuro
19.
Am J Reprod Immunol ; 91(3): e13830, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38454570

RESUMEN

PROBLEM: Endometriosis exhibits several immune dysfunctions, including deficient natural killer (NK) cell cytotoxicity. MICA (MHC class I chain-related molecule A) is induced by biological stress and soluble MICA (sMICA) negatively modulates the expression of the activating receptor, NKG2D, reducing NK cells activities. We investigated the involvement of soluble MICA in NK cell-deficient activity in endometriosis. METHODS OF STUDY: sMICA levels (serum and peritoneal fluid-PF) were evaluated by ELISA. Circulating NK cell subsets quantification and its NKG2D receptor expression, NK cell cytotoxicity and CD107a, IFN-γ and IL-10 expressions by NK cells stimulated with K562 cells were determined by flow cytometry. RESULTS: We found higher sMICA levels (serum and PF) in endometriosis, especially in advanced and deep endometriosis. Endometriosis presented lower percentages of CD56dim CD16+ cytotoxic cells and impaired NK cell responses upon stimulation, resulting in lower CD107a and IFN-γ expressions, and deficient NK cell cytotoxicity. NK cell stimulation in the MICA-blocked condition (mimicking the effect of sMICA) showed decreased cytotoxicity in initial endometriosis stages and the emergence of a negative correlation between CD107a expression and sMICA levels. CONCLUSIONS: We suggest that soluble MICA is a potential player in endometriosis pathophysiology with involvement in disease progression and severity, contributing to NK cell impaired IFN-γ response and degranulation. NK cell compartment exhibits multiple perturbations, including quantitative deficiency and impaired cytotoxicity, contributing to inadequate elimination of ectopic endometrial tissue.


Asunto(s)
Endometriosis , Femenino , Humanos , Degranulación de la Célula , Células Asesinas Naturales , Expresión Génica , Progresión de la Enfermedad , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo
20.
RSC Chem Biol ; 5(3): 167-188, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38456038

RESUMEN

In structural terms, the sialic acids are a large family of nine carbon sugars based around an alpha-keto acid core. They are widely spread in nature, where they are often found to be involved in molecular recognition processes, including in development, immunology, health and disease. The prominence of sialic acids in infection is a result of their exposure at the non-reducing terminus of glycans in diverse glycolipids and glycoproteins. Herein, we survey representative aspects of sialic acid structure, recognition and exploitation in relation to infectious diseases, their diagnosis and prevention or treatment. Examples covered span influenza virus and Covid-19, Leishmania and Trypanosoma, algal viruses, Campylobacter, Streptococci and Helicobacter, and commensal Ruminococci.

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