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1.
Cell ; 185(5): 881-895.e20, 2022 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-35216672

RESUMEN

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.


Asunto(s)
COVID-19/complicaciones , COVID-19/diagnóstico , Convalecencia , Inmunidad Adaptativa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Biomarcadores/metabolismo , Proteínas Sanguíneas/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , COVID-19/inmunología , COVID-19/patología , COVID-19/virología , Progresión de la Enfermedad , Femenino , Humanos , Inmunidad Innata/genética , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , Transcriptoma , Adulto Joven , Síndrome Post Agudo de COVID-19
2.
Int J Mol Sci ; 23(1)2021 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-35008723

RESUMEN

Type 2 diabetes (T2D) is a deficiency in how the body regulates glucose. Uncontrolled T2D will result in chronic high blood sugar levels, eventually resulting in T2D complications. These complications, such as kidney, eye, and nerve damage, are even harder to treat. Identifying individuals at high risk of developing T2D and its complications is essential for early prevention and treatment. Numerous studies have been done to identify biomarkers for T2D diagnosis and prognosis. This review focuses on recent T2D biomarker studies based on circulating nucleic acids using different omics technologies: genomics, transcriptomics, and epigenomics. Omics studies have profiled biomarker candidates from blood, urine, and other non-invasive samples. Despite methodological differences, several candidate biomarkers were reported for the risk and diagnosis of T2D, the prognosis of T2D complications, and pharmacodynamics of T2D treatments. Future studies should be done to validate the findings in larger samples and blood-based biomarkers in non-invasive samples to support the realization of precision medicine for T2D.


Asunto(s)
Biomarcadores/sangre , Ácidos Nucleicos Libres de Células/sangre , Diabetes Mellitus Tipo 2/sangre , Animales , Biomarcadores/orina , Ácidos Nucleicos Libres de Células/orina , Metilación de ADN/genética , Diabetes Mellitus Tipo 2/orina , Epigenómica , Humanos , Transcriptoma/genética
3.
Vaccine X ; 14: 100354, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37519778

RESUMEN

Introduction: Hepatitis B remains a global problem with no effective treatment. Here, a mucosal vaccine candidate was developed with HBsAg and HBcAg, to provide both prophylactic and therapeutic protection against hepatitis B. The antigens were presented using the P particle of human norovirus (HuNov). As a result, the chimeric HBV - HuNoV P particle can act as a dual vaccine for hepatitis B and HuNoV. Methods: The vaccine candidate was expressed and purified from Escherichia coli BL21 (DE3) cells. HBV-HuNoV chimeric P particles were successfully expressed and isolated, with sizes of approximately 25.64 nm. Then, the HBV-HuNoV chimeric P particles were evaluated for safety and immunogenicity in mice and gnotobiotic (Gn) pigs. After three doses (5 µg/dose in mice and 200 µg/dose in Gn pigs) of intranasal immunization, humoral and cellular immune responses, as well as toxicity, were evaluated. Results: The vaccine candidate induced strong HBV-HuNoV specific IFN-γ producing T-cell responses in the ileum, spleen, and blood of Gn pigs. Serum IgG and IgA antibodies against HBV-HuNoV chimeric P particles also increased significantly in Gn pigs. Increased HBsAg- and HuNoV-specific serum IgG responses were observed in mice and Gn pigs, although not statistically significant. The vaccine candidate did not show any toxicity in mice. Conclusions: In summary, the chimeric HBV-HuNoV P particle vaccine given intranasally was safe and induced strong cellular and humoral immune responses in Gn pig. Modifications to the vaccine structure and dosage need to be evaluated in future studies to further enhance immunogenicity and induce more balanced humoral and cellular responses.

4.
Obesity (Silver Spring) ; 30(2): 435-446, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35088558

RESUMEN

OBJECTIVE: This study aimed to evaluate microRNAs (miRNAs) as predictive biomarkers for type 2 diabetes (T2D) remission 12 months after sleeve gastrectomy (SG). METHODS: A total of 179 serum miRNAs were profiled, and 26 clinical variables were collected from 46 patients. Two patients were later excluded because of hemolysis, and six patients with unclear remission status were set aside to evaluate the prediction models. The remaining 38 patients were included for model building. Variable selection was done using different approaches, including Least Absolute Shrinkage and Selection Operator (LASSO). Prediction models were then developed using LASSO and assessed in the validation set. RESULTS: A total of 26 out of 38 patients achieved T2D remission 12 months after SG. The prediction model with only clinical variables misclassified two patients, which were correctly classified using miRNAs. Two miRNA-only models achieved an accuracy of one but performed poorly for the validation set. The best miRNA model was a mixed model (accuracy: 0.974) containing four miRNAs (hsa-miR-32-5p, hsa-miR-382-5p, hsa-miR-1-3p, and hsa-miR-21-5p) and four clinical variables (T2D medication, sex, age, and fasting blood glucose). These miRNAs are involved in pathways related to obesity and insulin resistance. CONCLUSIONS: This study suggests that four serum miRNAs might be predictive biomarkers for T2D remission 12 months after SG, but further validation studies are needed.


Asunto(s)
Diabetes Mellitus Tipo 2 , MicroARNs , Biomarcadores , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirugía , Gastrectomía , Humanos , MicroARNs/metabolismo , Proyectos Piloto
5.
Nutrients ; 14(1)2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-35011090

RESUMEN

Obesity rates among children are growing rapidly worldwide, placing massive pressure on healthcare systems. Untargeted metabolomics can expand our understanding of the pathogenesis of obesity and elucidate mechanisms related to its symptoms. However, the metabolic signatures of obesity in children have not been thoroughly investigated. Herein, we explored metabolites associated with obesity development in childhood. Untargeted metabolomic profiling was performed on fasting serum samples from 27 obese Caucasian children and adolescents and 15 sex- and age-matched normal-weight children. Three metabolomic assays were combined and yielded 726 unique identified metabolites: gas chromatography-mass spectrometry (GC-MS), hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC-MS/MS), and lipidomics. Univariate and multivariate analyses showed clear discrimination between the untargeted metabolomes of obese and normal-weight children, with 162 significantly differentially expressed metabolites between groups. Children with obesity had higher concentrations of branch-chained amino acids and various lipid metabolites, including phosphatidylcholines, cholesteryl esters, triglycerides. Thus, an early manifestation of obesity pathogenesis and its metabolic consequences in the serum metabolome are correlated with altered lipid metabolism. Obesity metabolite patterns in the adult population were very similar to the metabolic signature of childhood obesity. Identified metabolites could be potential biomarkers and used to study obesity pathomechanisms.


Asunto(s)
Biomarcadores/sangre , Metabolómica/métodos , Obesidad Infantil/sangre , Adolescente , Aminoácidos de Cadena Ramificada/sangre , Índice de Masa Corporal , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lípidos/sangre , Masculino , Fosfatidilcolinas/sangre , Polonia , Espectrometría de Masas en Tándem
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