Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 81
Filtrar
1.
Immunology ; 170(3): 401-418, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37605469

RESUMEN

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.

2.
Mol Ther ; 27(4): 837-849, 2019 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-30448196

RESUMEN

With the presence of the blood-brain barrier (BBB), successful immunotherapeutic drug delivery to CNS malignancies remains a challenge. Immunomodulatory agents, such as cytokines, can reprogram the intratumoral microenvironment; however, systemic cytokine delivery has limited access to the CNS. To bypass the limitations of systemically administered cytokines, we investigated if RNA-modified T cells could deliver macromolecules directly to brain tumors. The abilities of T cells to cross the BBB and mediate direct cytotoxic killing of intracranial tumors make them an attractive tool as biological carriers. Using T cell mRNA electroporation, we demonstrated that activated T cells can be modified to secrete granulocyte macrophage colony-stimulating factor (GM-CSF) protein while retaining their inherent effector functions in vitro. GM-CSF RNA-modified T cells effectively delivered GM-CSF to intracranial tumors in vivo and significantly extended overall survival in an orthotopic treatment model. Importantly, GM-CSF RNA-modified T cells demonstrated superior anti-tumor efficacy as compared to unmodified T cells alone or in combination with systemic administration of recombinant GM-CSF. Anti-tumor effects were associated with increased IFN-γ secretion locally within the tumor microenvironment and systemic antigen-specific T cell expansion. These findings demonstrate that RNA-modified T cells may serve as a versatile platform for the effective delivery of biological agents to CNS tumors.


Asunto(s)
Neoplasias Encefálicas/terapia , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/biosíntesis , Inmunoterapia Adoptiva/métodos , ARN/genética , Linfocitos T/metabolismo , Animales , Barrera Hematoencefálica/metabolismo , Neoplasias Encefálicas/mortalidad , Línea Celular Tumoral , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Proteínas Fluorescentes Verdes/metabolismo , Interferón gamma/biosíntesis , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Transfección/métodos , Microambiente Tumoral/genética
3.
Microsc Microanal ; 25(1): 244-249, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30073938

RESUMEN

Statoliths are nonskeletal calcified structures included in most invertebrates' gravireceptors. They have been identified and characterized in several gastropod and cephalopod molluscs and have proved to be very useful for age estimation, growth studies, and connectivity analysis, among other applications. Beyond the scarce available records on their occurrence in Class Bivalvia, statoliths are yet to be documented in the grooved carpet shell, Ruditapes decussatus, a species of high ecological and commercial value. An easy method for the extraction and processing of R. decussatus statoliths is described herein. The statolith growth was followed from the initial shell length (SL) of 2.5-3.5 mm (seed commercial size T1.5) for a period of 6 months in a nursery facility located in the Ria de Aveiro (an estuarine system in NW Portugal). The relationship between statolith diameter (StD) and SL follows the function StD=14.305 SL0.254 (N=173; r=0.855, p<0.001). All statoliths observed showed similar morphostructure and general chemistry: hard, translucent spheres of crystalline calcium oxalate (whewellite), with a central nucleus delimited by a growth check of 6.7±1.0 µm in diameter, possibly as a result of growth arrest during metamorphosis, a metamorphic ring, as described for their gastropod counterparts. Subsequent studies should validate this and will involve a search for the occurrence of additional checks that may potentially be present in older specimens and if they are, would open a new range of most promising applications for bivalve statoliths.


Asunto(s)
Bivalvos/fisiología , Membrana Otolítica/anatomía & histología , Animales , Sensación de Gravedad , Membrana Otolítica/crecimiento & desarrollo , Portugal
4.
J ECT ; 32(4): 262-266, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27327557

RESUMEN

BACKGROUND: Transcranial magnetic stimulation (TMS) is a promising noninvasive brain stimulation intervention. Transcranial magnetic stimulation has been proposed for obsessive-compulsive disorder (OCD) with auspicious results. OBJECTIVE: To assess the efficacy of TMS for OCD in randomized clinical trials (RCTs). METHODS: Systematic review using MEDLINE and EMBASE from the first RCT available until March 11, 2016. The main outcome was the Hedges g for continuous scores for Yale-Brown Obsessive Compulsive Scale in a random-effects model. Heterogeneity was evaluated with the I and the χ test. Publication bias was evaluated using the Begg funnel plot. Metaregression was performed using the random-effects model modified by Knapp and Hartung. RESULTS: We included 15 RCTs (n = 483), most had small-to-modest sample sizes. Comparing active versus sham TMS, active stimulation was significantly superior for OCD symptoms (Hedges g = 0.45; 95% confidence interval, 0.2-0.71). The funnel plot showed that the risk of publication bias was low and between-study heterogeneity was low (I = 43%, P = 0.039 for the χ test). Metaregression showed no particular influence of any variable on the results. CONCLUSIONS: Transcranial magnetic stimulation active was superior to sham stimulation for the amelioration of OCD symptoms. Trials had moderate heterogeneity results, despite different protocols of stimulation used. Further RCTs with larger sample sizes are fundamentally needed to clarify the precise impact of TMS in OCD symptoms.


Asunto(s)
Trastorno Obsesivo Compulsivo/terapia , Estimulación Magnética Transcraneal/métodos , Adulto , Terapia Electroconvulsiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/psicología , Adulto Joven
5.
J Environ Sci Health B ; 51(7): 465-8, 2016 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-27052932

RESUMEN

Carrot (Daucus carota L.) is a vegetable crop that is grown throughout the year across various regions of Brazil in rotation or in succession to other cultures. Herbicide residual effect has emerged as a concern, because of the possibility of carryover. Thus, the objective of this study was to evaluate the effect of tembotrione and atrazine residues - in mixture and isolated - on carrot planted in succession to corn. The experiment was designed in randomized blocks with five replications. Treatments consisted of tembotrione (50.4 g ha(-1)), tembotrione (100.8 g ha(-1)), tembotrione + atrazine (50.4 g ha(-1)+ 2 L ha(-1)), tembotrione + atrazine (100.8 g ha(-1)+ 2 L ha(-1)), and atrazine (2.00 L ha(-1)) applied eight months before carrot seeding, plus a control treatment with no herbicide application. Investigated variables were shoot dry mass, productivity, and classification of carrot roots. The presence of atrazine and tembotrione decreased dry mass in the area, and only tembotrione reduced total root productivity. Thus, there is a carryover effect to tembotrione application that reduces the dry matter accumulation of shoot and total productivity, and an atrazine + tembotrione (100.8 g ha(-1)) mixture reduces the total productivity after application of these herbicides to soil.


Asunto(s)
Atrazina/efectos adversos , Ciclohexanonas/efectos adversos , Daucus carota/efectos de los fármacos , Herbicidas/efectos adversos , Residuos de Plaguicidas/efectos adversos , Contaminantes del Suelo/efectos adversos , Sulfonas/efectos adversos , Brasil , Daucus carota/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/crecimiento & desarrollo
6.
J Struct Biol ; 186(2): 292-301, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24709579

RESUMEN

Gastropod statoliths are spherical biocarbonates formed during their lifespan. The stability and homogeneity of these structures' mineral matrix was characterised along their radiuses, using Nassarius reticulatus as a model. Generally, they were proved to be bimineralic. Two of the three CaCO3 crystalline polymorphs occurring in biocarbonates - aragonite and calcite - coexist along statolith radiuses, aragonite being unequivocally the most abundant phase. The presence of a diffuse organic matrix was also perceived by the detection of a weak Raman band between 2800 and 3000 cm(-1) consistently observed along radiuses. Beyond the apparent stability and homogeneity, different crystalline orientations were disclosed by Raman spectroscopy. A change in the intensity pattern of the features related to the lattice and bending modes of aragonite between different radiuses give new insights for a possible spherulitic-like growth of these structures. As expected from the relative homogeneity of both mineral and organic signals, there was no pattern on the distribution of Ca, O, Na and S along radiuses. However, a higher concentration of Sr occurs in growth rings (known as winter tags), corroborating the already described negative correlation between the concentration of this element in statoliths and temperature. Despite the apparent stability and homogeneity of the matrix during its lifespan, the periodic distribution of Sr potentially influences a dissimilar incorporation of trace elements in increments and growth rings. Since gastropod statolith elemental fingerprinting was recently suggested as a new tool to monitor marine environmental changes, the pressing need for further studies on the incorporation of traces in these structures is highlighted.


Asunto(s)
Bicarbonatos/análisis , Carbonato de Calcio/análisis , Membrana Otolítica/química , Membrana Otolítica/ultraestructura , Animales , Microanálisis por Sonda Electrónica , Gastrópodos , Espectrometría Raman , Estroncio/análisis , Temperatura , Difracción de Rayos X
7.
J Obes ; 2024: 7204607, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38831961

RESUMEN

Obesity is a complex chronic disease characterized by excess body fat (adipose) that is harmful to health and has been a major global health problem. It may be associated with several diseases, such as nonalcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) are lipid mediators that have anti-inflammatory characteristics and can be found in animals and plants, with capybara oil (CO) being a promising source. So, we intend to evaluate the hepatic pathophysiological alterations in C57Bl/6 mice with NAFLD, caused by obesity, and the possible beneficial effects of OC in the treatment of this disease. Eighteen 3-month-old male C57Bl/6 mice received a control or high-fat diet for 18 weeks. From the 15th to the 18th week, the animals received treatment-through orogastric gavage-with placebo or free capybara oil (5 g/kg). Parameters inherent to body mass, glucose tolerance, evaluation of liver enzymes, percentage of hepatic steatosis, oxidative stress, the process of cell death with the apoptotic biomarkers (Bax, Bcl2, and Cytochrome C), and the ultrastructure of hepatocytes were analyzed. Even though the treatment with CO was not able to disassemble the effects on the physiological parameters, it proved to be beneficial in reversing the morphological and ultrastructural damage present in the hepatocytes. Thus, demonstrating that CO has beneficial effects in reducing steatosis and the apoptotic pathway, it is a promising treatment for NAFLD.


Asunto(s)
Apoptosis , Hígado , Enfermedad del Hígado Graso no Alcohólico , Aceites , Roedores , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/terapia , Masculino , Animales , Ratones , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hepatocitos/ultraestructura , Aceites/farmacología , Aceites/uso terapéutico , Obesidad/complicaciones , Apoptosis/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/ultraestructura , Oxidorreductasas/metabolismo , Activación Enzimática/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos
8.
Mol Ther Methods Clin Dev ; 32(1): 101192, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38327807

RESUMEN

The COVID-19 pandemic has caused about seven million deaths worldwide. Preventative vaccines have been developed including Spike gp mRNA-based vaccines that provide protection to immunocompetent patients. However, patients with primary immunodeficiencies, patients with cancer, or hematopoietic stem cell transplant recipients are not able to mount robust immune responses against current vaccine approaches. We propose to target structural SARS-CoV-2 antigens (i.e., Spike gp, Membrane, Nucleocapsid, and Envelope) using circulating human antigen-presenting cells electroporated with full length SARS-CoV-2 structural protein-encoding mRNAs to activate and expand specific T cells. Based on the Th1-type cytokine and cytolytic enzyme secretion upon antigen rechallenge, we were able to generate SARS-CoV-2 specific T cells in up to 70% of unexposed unvaccinated healthy donors (HDs) after 3 subsequent stimulations and in 100% of recovered patients (RPs) after 2 stimulations. By means of SARS-CoV-2 specific TCRß repertoire analysis, T cells specific to Spike gp-derived hypomutated regions were identified in HDs and RPs despite viral genomic evolution. Hence, we demonstrated that SARS-CoV-2 mRNA-loaded antigen-presenting cells are effective activating and expanding COVID19-specific T cells. This approach represents an alternative to patients who are not able to mount adaptive immune responses to current COVID-19 vaccines with potential protection across new variants that have conserved genetic regions.

9.
Foods ; 13(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38790865

RESUMEN

In this study, the oils of açaí, passion fruit, pequi, and guava were submitted to physicochemical analysis to investigate their potential application in the food industry. Gas chromatography associated with mass spectroscopy showed that oleic and linoleic acids are mainly responsible for the nutritional quality of açaí, passion fruit, pequi, and guava oils, which exhibited 46.71%, 38.11%, 43.78%, and 35.69% of the former fatty acid, and 18.93%, 47.64%, 20.90%, and 44.72% of the latter, respectively. The atherogenicity index of the oils varied from 0.11 to 0.65, while the thrombogenicity index was 0.93 for açaí, 0.35 for guava, and 0.3 for passion fruit oils, but 1.39 for pequi oil, suggesting that the use of the first three oils may lead to a low incidence of coronary heart disease. Thermogravimetry showed that all tested oils were thermally stable above 180 °C; therefore, they can be considered resistant to cooking and frying temperatures. In general, the results of this study highlight possible applications of these oils in the food industry, either in natura or in typical food production processes.

10.
Nutrients ; 15(13)2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37447251

RESUMEN

Obesity is an inflammatory disease associated with secondary diseases such as kidney disease, which can cause lipotoxicity, inflammation and loss of organ function. Polyunsaturated fatty acids act in the production of lipid mediators and have anti-inflammatory characteristics. In this work, the objective was to evaluate renal histopathology in obese mice and the effects of treatment with capybara oil (CO) (5000 mg/kg/day for 4 weeks). Parameters such as body mass, lipid profile, systolic blood pressure, urinary creatinine and protein excretion, structure and ultrastructure of the renal cortex, fibrosis, tissue inflammation and oxidative stress were analyzed. CO treatment in obese mice showed improvement in the lipid profile and reduction in systolic blood pressure levels, in addition to beneficial remodeling of the renal cortex. Our data demonstrated that CO decreased inflammation, oxidative stress and renal fibrosis, as evidenced by quantifying the expression of TNF-α, IL-10, CAT, SOD, α-SMA and TGF-ß. Although treatment with CO did not show improvement in renal function, ultrastructural analysis showed that the treatment was effective in restoring podocytes and pedicels, with restructuring of the glomerular filtration barrier. These results demonstrate, for the first time, that treatment with CO is effective in reducing kidney damage, being considered a promising treatment for obesity.


Asunto(s)
Enfermedades Renales , Roedores , Ratones , Animales , Ratones Obesos , Riñón/metabolismo , Inflamación/metabolismo , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Estrés Oxidativo , Obesidad/metabolismo , Fibrosis , Lípidos/farmacología
11.
Nutrients ; 15(24)2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38140293

RESUMEN

Cholesterol is a pivotal lipotoxic molecule that contributes to the progression of Non-Alcoholic Steatohepatitis NASH). Additionally, microcirculatory changes are critical components of Non-Alcoholic Fatty Liver Disease (NAFLD) pathogenesis. This study aimed to investigate the role of cholesterol as an insult that modulates microcirculatory damage in NAFLD and the underlying mechanisms. The experimental model was established in male C57BL/6 mice fed a high-fat high-carbohydrate (HFHC) diet for 39 weeks. Between weeks 31-39, 2% cholesterol was added to the HFHC diet in a subgroup of mice. Leukocyte recruitment and hepatic stellate cells (HSC) activation in microcirculation were assessed using intravital microscopy. The hepatic microvascular blood flow (HMBF) was measured using laser speckle flowmetry. High cholesterol levels exacerbated hepatomegaly, hepatic steatosis, inflammation, fibrosis, and leukocyte recruitment compared to the HFHC group. In addition, cholesterol decreased the HMBF-cholesterol-induced activation of HSC and increased HIF1A expression in the liver. Furthermore, cholesterol promoted a pro-inflammatory cytokine profile with a Th1-type immune response (IFN-γ/IL-4). These findings suggest cholesterol exacerbates NAFLD progression through microcirculatory dysfunction and HIF1A upregulation through hypoxia and inflammation. This study highlights the importance of cholesterol-induced lipotoxicity, which causes microcirculatory dysfunction associated with NAFLD pathology, thus reinforcing the potential of lipotoxicity and microcirculation as therapeutic targets for NAFLD.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Masculino , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Microcirculación , Factor 1 Inducible por Hipoxia/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismo , Colesterol/metabolismo , Inflamación/metabolismo , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad
12.
Biochim Biophys Acta Gen Subj ; 1867(4): 130314, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36693453

RESUMEN

Subclinical acute kidney injury (subAKI) is characterized by tubule-interstitial injury without significant changes in glomerular function. SubAKI is associated with the pathogenesis and progression of acute and chronic kidney diseases. Currently, therapeutic strategies to treat subAKI are limited. The use of gold nanoparticles (AuNPs) has shown promising benefits in different models of diseases. However, their possible effects on subAKI are still unknown. Here, we investigated the effects of AuNPs on a mouse model of subAKI. Animals with subAKI showed increased functional and histopathologic markers of tubular injury. There were no changes in glomerular function and structure. The animals with subAKI also presented an inflammatory profile demonstrated by activation of Th1 and Th17 cells in the renal cortex. This phenotype was associated with decreased megalin-mediated albumin endocytosis and expression of proximal tubular megalin. AuNP treatment prevented tubule-interstitial injury induced by subAKI. This effect was associated with a shift to an anti-inflammatory Th2 response. Furthermore, AuNP treatment preserved megalin-mediated albumin endocytosis in vivo and in vitro. AuNPs were not nephrotoxic in healthy mice. These results suggest that AuNPs have a protective effect in the tubule-interstitial injury observed in subAKI, highlighting a promising strategy as a future antiproteinuric treatment.


Asunto(s)
Lesión Renal Aguda , Nanopartículas del Metal , Ratones , Animales , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Oro/farmacología , Túbulos Renales Proximales , Modelos Animales de Enfermedad , Proteinuria/metabolismo , Proteinuria/patología , Albúminas/metabolismo , Lesión Renal Aguda/metabolismo
14.
Sci Total Environ ; 832: 154892, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-35378190

RESUMEN

Particulate matter (PM) and pollen interaction, either airborne or at the respiratory mucosa needs further clarification, as allergic reaction intensification can be related to the PM physical characteristics and toxicity. This study aimed to investigate the physical-chemical properties of PM that can adhere to the pollen wall during its transport or inhalation, using Quercus spp. as a model, in three Portuguese cities with different geographical locations, meteorological influence and urbanization levels. Possible sources were evaluated through air masses trajectory analysis using the HYSPLIT model and correlation with meteorological factors. The sampling was performed using a 7-days Hirst-type volumetric sampler, and the pollen grains were observed using a Field Emission Electron Probe Microanalyser for PM analysis. A secondary electron image of each pollen grain was taken, to determine the adhered particles characteristics and energy dispersive x-ray spectroscopy (EDS) spectra were obtained for individual particles. A total of 484 pollen grains was observed, with 7683 particles counted and 1914 EDS spectra analyzed. The particle's equivalent diameter ranged from 0.3-16 µm, with most having a diameter < 3 µm. For the three cities, there were significant differences in the number of particles per pollen and the % area occupied by the particles. Particles adhered were mainly Si-rich, but variations in other dominant groups were observed. For Évora and Guarda, Ca-rich, SO-rich were second and third more representative, while Porto were Organic and Cl-rich. Metals&Oxides were found in all cities with the highest number in Porto. P-rich particles were only found in Évora. Sea salt particles were observed in Évora, coincide with air mass trajectories possible carrying them from the Mediterranean Sea. In conclusion, the PM physical characteristics are similar between the studied cities, however, the dominant chemical composition is different, certainly impacting the exposome influence and pollen-allergy intensification towards the same pollen type and concentration.


Asunto(s)
Contaminantes Atmosféricos , Quercus , Contaminantes Atmosféricos/análisis , Ciudades , Monitoreo del Ambiente/métodos , Tamaño de la Partícula , Material Particulado/análisis , Polen/química
15.
J Immunol Res ; 2022: 8191253, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35465348

RESUMEN

Objective: To assess the clinical efficacy of flavonoid supplements on allergic diseases. Design: Systematic review. Data Sources. MEDLINE/PubMed, Scopus, Web of Science, and Embase databases were searched from inception to September 2021. Eligibility Criteria for Selecting Studies. Eligible study designs were randomized controlled trials that investigated the effect of flavonoids applied to allergic diseases. Results: This review included 15 randomized controlled trials, including allergic rhinitis/cedar pollinosis (n = 10), asthma (n = 3), and atopic dermatitis (n = 2). A total of 990 participants aged 6 to 69 years were included in these studies. Globally, 12 studies (80%) revealed some benefits of flavonoids (isolate or combined with other compounds) in allergic patients, while three studies (20%) reported no statistically significant impact on symptom scores and/or lung function. No severe adverse events related to treatment were reported. According to the GRADE system, the outcomes evaluated were of low to moderate quality of evidence. Conclusions: Overall, this review suggests that the administration of flavonoids may provide a viable strategy for mitigating allergic symptoms. Future trials with high methodological quality are needed to establish definitive conclusions. This trial is registered with PROSPERO registration no. CRD42021237403.


Asunto(s)
Asma , Rinitis Alérgica Estacional , Rinitis Alérgica , Asma/tratamiento farmacológico , Flavonoides/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica Estacional/tratamiento farmacológico
16.
Braz J Psychiatry ; 44(1): 26-34, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34190825

RESUMEN

OBJECTIVE: To test the hypothesis that genetic variations of cannabinoid receptors contribute to the pathophysiology of cognitive deficits in schizophrenia. METHODS: In this genetic association case-control study, cannabinoid receptor polymorphisms CNR1 rs12720071 and CNR2 rs2229579 were tested for association with neurocognitive performance in 69 patients with schizophrenia and 45 healthy controls. Neurocognition was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS). RESULTS: We found a consistent association between CNR1 rs12720071 polymorphism and the cognitive performance of patients in several cognitive domains. Patients with C/C polymorphism presented significantly worse performance in motor speed, verbal fluency, attention/processing speed and reasoning/problem solving. CONCLUSION: Although limited, our data support the hypothesis that CNR1 variations may be associated with the pathogenesis of cognitive deficits of schizophrenia.


Asunto(s)
Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB2/genética , Esquizofrenia , Estudios de Casos y Controles , Cognición , Humanos , Pruebas Neuropsicológicas , Polimorfismo Genético , Esquizofrenia/genética
17.
Cells ; 11(5)2022 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-35269381

RESUMEN

Annexin-A1 (AnxA1) and its N-terminal derived peptide Ac2-26 regulate the inflammatory response in several experimental models of disorders. This study evaluated the effect of endogenous AnxA1 and its N-terminal peptide Acetyl 2-26 (Ac2-26) on allergic asthma triggered by house dust mite (HDM) extract in mice. ANXA1-/- and wildtype (WT) mice were exposed to intranasal instillation of HDM every other day for 3 weeks, with analyses performed 24 h following the last exposure. Intranasal administration of peptide Ac2-26 was performed 1 h before HDM, beginning 1 week after the initial antigen application. ANXA1-/- mice stimulated with HDM showed marked exacerbations of airway hyperreactivity (AHR), eosinophil accumulation, subepithelial fibrosis, and mucus hypersecretion, all parameters correlating with overexpression of cytokines (IL-4, IL-13, TNF-α, and TGF-ß) and chemokines (CCL11/eotaxin-1 and CCL2/MCP-1). Intranasal treatment with peptide Ac2-26 decreased eosinophil infiltration, peribronchiolar fibrosis, and mucus exacerbation caused by the allergen challenge. Ac2-26 also inhibited AHR and mediator production. Collectively, our findings show that the AnxA1-derived peptide Ac2-26 protects against several pathological changes associated with HDM allergic reaction, suggesting that this peptide or related AnxA1-mimetic Ac2-26 may represent promising therapeutic candidates for the treatment of allergic asthma.


Asunto(s)
Asma , Inflamación , Alérgenos , Animales , Asma/tratamiento farmacológico , Citocinas , Fibrosis , Inflamación/tratamiento farmacológico , Inflamación/patología , Ratones , Péptidos/farmacología , Péptidos/uso terapéutico
18.
J Psychiatr Res ; 149: 331-338, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34785039

RESUMEN

OBJECTIVES: To investigate the association between cytokine peripheral levels and the risk of cardiovascular disease in patients with schizophrenia and controls. METHODS: A sample of 40 patients and 40 control subjects participated in the study. Psychiatric diagnosis was established following structured clinical assessment. The Framingham Score was used to assess cardiovascular risk (CVR). Serum levels of the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were determined by cytometric bead array (CBA) technique, and the serum levels of IL-33, sST2, sTNFR1, sTNFR2, Leptin and Adiponectin by Enzyme-Linked Immunosorbent assay (ELISA). RESULTS: Patients with schizophrenia showed greater frequency of moderate CVR when compared with controls (p = 0.14). In addition, patients showed higher levels of sTNFR2 and Adiponectin compared to controls (p = 0.007 and p < 0.001, respectively). Adiponectin and sTNFR2 were associated with CVR only in patients (p = 0.0002 and p = 0.033, respectively). In multivariate analysis controlling for socio-demographic and clinical confounders, illness duration (r = 0.492; p < 0.002) and sTNFR2 (r = 0.665; p < 0.004) were independent predictors of CVR. CONCLUSION: Our results reinforce the concept that patients with schizophrenia are at greater risk to develop cardiovascular diseases, and suggest that the associated chronic low-grade inflammation might play a role in this process.


Asunto(s)
Enfermedades Cardiovasculares , Esquizofrenia , Adiponectina , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Citocinas , Ensayo de Inmunoadsorción Enzimática , Humanos , Inflamación , Receptores Tipo I de Factores de Necrosis Tumoral , Receptores Tipo II del Factor de Necrosis Tumoral , Factores de Riesgo , Esquizofrenia/complicaciones , Factor de Necrosis Tumoral alfa
19.
Pharmaceuticals (Basel) ; 15(11)2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36422543

RESUMEN

Pickering emulsions are systems composed of two immiscible fluids stabilized by organic or inorganic solid particles. These solid particles of certain dimensions (micro- or nano-particles), and desired wettability, have been shown to be an alternative to conventional emulsifiers. The use of biodegradable and biocompatible stabilizers of natural origin, such as clay minerals, presents a promising future for the development of Pickering emulsions and, with this, they deliver some advantages, especially in the area of biomedicine. In this review, the effects and characteristics of microparticles in the preparation and properties of Pickering emulsions are presented. The objective of this review is to provide a theoretical basis for a broader type of emulsion, in addition to reviewing the main aspects related to the mechanisms and applications to promote its stability. Through this review, we highlight the use of this type of emulsion and its excellent properties as permeability promoters of solid particles, providing ideal results for local drug delivery and use in Pickering emulsions.

20.
Polymers (Basel) ; 14(14)2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-35890687

RESUMEN

The industrial processing of fruits in the Amazon region, such as tucuma, generates a large amount of coproducts with great nutritional potential. In this work, phenolic compounds from tucuma coproduct almonds were extracted and microencapsulated by spray drying using maltodextrin as the encapsulating agent and verified its antioxidant activity. Phenolic compounds were determined by UV spectroscopy and identified by Ultraefficiency Liquid Chromatography. Antioxidant activity was measured by ABTS and DPPH assay. Thermogravimetric techniques, infrared spectroscopy, scanning electron microscopy, moisture content and water activity were applied to characterize the microparticle. The crude extract and microparticle had total polyphenols of 135.1 mg/g ± 0.078 and 130.5 mg/g ± 0.024, respectively. Caffeic and gallic acids were identified. The crude extract and the microparticle showed good antioxidant activity by ABTS and DPPH assay, justified by the presence of the phenolic compounds found. The microparticle showed spherical and heterogeneous structures and good encapsulation efficiency from the spray drying process using maltodextrin. The results show that the extract of the tucuma almond coproduct can be used as a phenolic compound-rich source and microencapsulated with possible application for functional food production.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA