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1.
Acta otorrinolaringol. esp ; 75(2): 94-101, Mar-Abr. 2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-231381

RESUMO

Introducción: El PIV (pan-immune-inflammation value), un índice que resulta del cociente (neutrófilos×monocitos×plaquetas) / linfocitos, ha sido propuesto como un biomarcador con capacidad pronóstica en diferentes modelos tumorales. El objetivo del presente estudio es analizar la capacidad pronóstica del PIV en pacientes con carcinoma escamoso de cabeza y cuello. Pacientes y métodos: Estudio retrospectivo de 1.187 pacientes con carcinoma escamoso de cabeza y cuello tratados en nuestro centro durante el periodo 2000-2017. Se obtuvo el valor del PIV a partir de un análisis realizado en un intervalo inferior a las 3 semanas previas al inicio del tratamiento. Resultados: El valor del PIV se relacionó de forma significativa con el consumo de tóxicos (p=0,001), la localización del tumor (0,0001), la extensión tumoral (0,0001), y el grado histológico (0,016). Mediante un análisis de partición recursiva se definieron 4 categorías en función del valor del PIV: categoría i: PIV<136,3 (n=118; 9,9%), categoría ii: PIV 136,3-451,1 (n=594, 50,0%); categoría iii: PIV 451,1-1.141,2 (n=357; 30,1%); categoría iv: PIV>1.141,2 (n=118; 9,9%). Se pudo observar una reducción ordenada y significativa de la supervivencia específica a medida que se incrementaba la categoría en el valor del PIV. Esta disminución en la supervivencia se produjo de forma independiente al tipo de tratamiento, la extensión del tumor, o la localización del tumor primario. La categoría en el valor del PIV se relacionó de forma significativa con la supervivencia específica en un estudio multivariable. Conclusiones: El PIV es un biomarcador con capacidad pronóstica en los pacientes con carcinoma escamoso de cabeza y cuello.(AU)


Introduction: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils×monocytes×platelets) / lymphocytes, has been proposed as a prognostic biomarker in different tumor models. The aim of this study is to analyze the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma. Patients and methods: Retrospective study of 1,187 patients with head and neck squamous cell carcinoma treated at our center between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. Results: PIV value was significantly associated with toxic consumption (0.001), tumor location (0.0001), tumor extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category i: PIV<136.3 (n=118, 9.9%), category ii: PIV 136.3-451.1 (n=594, 50.0%), category iii: PIV 451.1-1,141.2 (n=357, 30.1%), and category iv: PIV>1,141.2 (n=118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumor extension, or location of the primary tumor. The PIV category was an independent prognostic factor of disease-specific survival in a multivariable study. Conclusions: PIV is a prognostic biomarker in patients with head and neck squamous cell carcinoma.(AU)


Assuntos
Humanos , Masculino , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço , Prognóstico , Biomarcadores , Contagem de Plaquetas , Linfócitos , Neutrófilos , Monócitos , Estudos Retrospectivos , Neoplasias/diagnóstico , Estudos de Coortes , Otolaringologia , Hipofaringe , Boca , Orofaringe
2.
Nefrología (Madrid) ; 44(2): 217-123, Mar-Abr. 2024. tab, graf
Artigo em Inglês | IBECS | ID: ibc-231571

RESUMO

Background and aim: In Fabry disease (FD), primary factors such as glycosphingolipid deposition that initiate kidney damage and secondary factors that advance kidney damage to fibrosis are different. Periostin is a molecule of proven importance in renal inflammation and fibrosis. It was previously shown that periostin plays an essential role in the process leading to renal fibrosis and its expression is increased in many kidney diseases. In the present study, we aimed to reveal the relationship between periostin and Fabry nephropathy. Material-method: This cross-sectional study included 18 FD patients (10 males, 8 females) with enzyme replacement therapy (ERT) indications and 22 healthy control patients of similar age and gender. At the time of diagnosis, plasma alpha-galactosidase A (α-gal-A) and globotriaosylsphingosine (lyso-Gb3), proteinuria, and kidney function tests of all FD patients before ERT were scanned from the hospital system. Periostin was studied from serum samples collected and stored before ERT. Parameters related to serum periostin levels in Fabry disease were investigated. Results: In FD patients, serum periostin was negatively correlated with age of first symptom and GFR; and positively correlated with proteinuria and lyso-Gb3. In regression analysis, we found that serum periostin was the only independent determinant of proteinuria in patients with Fabry disease. The serum periostin levels were significantly lower in patients with low proteinuria, and the serum periostin levels were correlated with proteinuria. Discussion: Periostin may be a valuable marker of Fabry nephropathy and proteinuria. Periostin seems to be one of the molecules that may have an important role in the management of the fibrotic process in Fabry nephropathy. We think that the role of periostin among these mechanisms is worth investigating... (AU)


Antecedente y objetivo: En la enfermedad de Fabry (EF), son diferentes los factores primarios tales como el depósito de glicoesfingolípidos que inicia el daño renal, y los factores secundarios que progresan de daño renal a fibrosis. Periostina es una molécula de importancia probada en la inflamación renal y la fibrosis. Se ha demostrado previamente que periostina juega un papel esencial en el proceso que causa la fibrosis renal, y que su expresión se incrementa en muchas enfermedades renales. En el presente estudio, nuestro objetivo fue revelar la relación entre la periostina y la nefropatía de Fabry. Material y método: Este estudio transversal incluyó 18 pacientes con EF (10 varones y 8 mujeres) con indicación de terapia enzimática (ERT) y 22 controles sanos con edad y sexo similares. En el momento del diagnóstico se escanearon del sistema hospitalario las pruebas de alfa-galactosidasa A (α-gal-A) plasmática y globotriaosilsfingosina (lyso-Gb3), proteinuria y función renal de todos los pacientes con EF antes de la ERT. Se analizó el nivel de periostina en las muestras séricas recogidas y almacenadas antes de realizar la ERT. Se investigaron los parámetros relacionados con los niveles séricos de periostina en la enfermedad de Fabry. Resultados: En los pacientes con EF, el nivel de periostina sérica se correlacionó negativamente con la edad del primer síntoma y la GFR, y positivamente con proteinuria y lyso-Gb3. En el análisis de regresión, encontramos que el nivel de periostina sérico fue el único determinante independiente de proteinuria en los pacientes con EF. Los niveles séricos de periostina fueron significativamente menores en los pacientes con baja proteinuria, correlacionándose los niveles séricos de periostina con proteinuria. Discusión: La periostina puede ser un marcador valioso de nefropatìa de Fabry y proteinuria.... (AU)


Assuntos
Humanos , Doença de Fabry , Proteinúria , Fibrose , Nefropatias , Terapia Enzimática , alfa-Galactosidase , Biomarcadores , Rim/lesões , Estudos Transversais
3.
Front Immunol ; 15: 1285813, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426091

RESUMO

Background: Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. Methods: To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Results: Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Conclusion: Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.


Assuntos
Doença da Artéria Coronariana , Placa Aterosclerótica , Humanos , Biomarcadores , Angiografia Coronária , Osteopontina/genética , Placa Aterosclerótica/patologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-38432772

RESUMO

In this report we provide a summary of the presentations and discussion of the latest knowledge regarding the buccal micronucleus (MN) cytome assay. This information was presented at the HUMN workshop held in Malaga, Spain, in connection with the 2023 European, Environmental Mutagenesis and Genomics conference. The presentations covered the most salient topics relevant to the buccal MN cytome assay including (i) the biology of the buccal mucosa, (ii) its application in human studies relating to DNA damage caused by environmental exposure to genotoxins, (iii) the association of buccal MN with cancer and a wide range of reproductive, metabolic, immunological, neurodegenerative and other age-related diseases, (iv) the impact of nutrition and lifestyle on buccal MN cytome assay biomarkers; (v) its potential for application to studies of DNA damage in children and obesity, and (vi) the growing prospects of enhancing the clinical utility by automated scoring of the buccal MN cytome assay biomarkers by image recognition software developed using artificial intelligence. The most important knowledge gap is the need of prospective studies to test whether the buccal MN cytome assay biomarkers predict health and disease.


Assuntos
Inteligência Artificial , Dano ao DNA , Criança , Humanos , Estudos Prospectivos , Exposição Ambiental , Biomarcadores
5.
Artigo em Chinês | MEDLINE | ID: mdl-38433697

RESUMO

Allergic rhinitis(AR) is a chronic inflammation of nasal mucosa mediated by IgE, which prevalence is increasing year by year. Allergen immunotherapy(AIT) has been proved to be effective in the treatment of AR. Patients can usually achieve satisfactory clinical remission after the standard course of treatment. At present, sIgE/tIgE is mainly used to evaluate the severity of allergy in patients with AR before immunotherapy, but there is no recognized biomarker for evaluating the efficacy of AIT. Based on the mechanism that immune cells participate in the formation of immune tolerance during AIT, this paper reviews the latest progress of immune cell markers in allergic rhinitis for the evaluation of the efficacy of AIT in recent years, in order to provide a more comprehensive evaluation basis for AR patients during immunotherapy.


Assuntos
Rinite Alérgica , Humanos , Rinite Alérgica/terapia , Dessensibilização Imunológica , Mucosa Nasal , Inflamação , Biomarcadores
6.
Front Immunol ; 15: 1327035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433830

RESUMO

Despite the numerous advantages of allogeneic hematopoietic stem cell transplants (allo-HSCT), there exists a notable association with risks, particularly during the preconditioning period and predominantly post-intervention, exemplified by the occurrence of graft-versus-host disease (GVHD). Risk stratification prior to symptom manifestation, along with precise diagnosis and prognosis, relies heavily on clinical features. A critical imperative is the development of tools capable of early identification and effective management of patients undergoing allo-HSCT. A promising avenue in this pursuit is the utilization of proteomics-based biomarkers obtained from non-invasive biospecimens. This review comprehensively outlines the application of proteomics and proteomics-based biomarkers in GVHD patients. It delves into both single protein markers and protein panels, offering insights into their relevance in acute and chronic GVHD. Furthermore, the review provides a detailed examination of the site-specific involvement of GVHD. In summary, this article explores the potential of proteomics as a tool for timely and accurate intervention in the context of GVHD following allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Biomarcadores , Condicionamento Psicológico , Proteômica
7.
Int J Nanomedicine ; 19: 1923-1949, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435755

RESUMO

Exosomes, small extracellular vesicles derived from cells, are known to carry important bioactive molecules such as proteins, nucleic acids, and lipids. These bioactive components play crucial roles in cell signaling, immune response, and tumor metastasis, making exosomes potential diagnostic biomarkers for various diseases. However, current methods for detecting tumor exosomes face scientific challenges including low sensitivity, poor specificity, complicated procedures, and high costs. It is essential to surmount these obstacles to enhance the precision and dependability of diagnostics that rely on exosomes. Merging DNA signal amplification techniques with the signal boosting capabilities of nanomaterials presents an encouraging strategy to overcome these constraints and improve exosome detection. This article highlights the use of DNA signal amplification technology and nanomaterials' signal enhancement effect to improve the detection of exosomes. This review seeks to offer valuable perspectives for the enhancement of amplification methods applied in practical cancer diagnosis and prognosis by providing an overview of how these novel technologies are utilized in exosome-based diagnostic procedures.


Assuntos
Exossomos , Vesículas Extracelulares , Neoplasias , Humanos , Neoplasias/diagnóstico , Biomarcadores , DNA
8.
PeerJ ; 12: e16957, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435987

RESUMO

Background: Telomeres are non-coding DNA repeats at the chromosome ends and their shortening is considered one of the major causes of aging. However, they also serve as a biomarker of environmental exposures and their length and attrition is affected by various stressors. In this study, we examined the average telomere length in Astyanax mexicanus, a species that has both surface-dwelling and cave-adapted populations. The cave morph descended from surface ancestors and adapted to a markedly different environment characterized by specific biotic and abiotic stressors, many of which are known to affect telomere length. Our objective was to explore whether telomere length differs between the two morphs and whether it serves as a biological marker of aging or correlates with the diverse environments the morphs are exposed to. Methods: We compared telomere length and shortening between laboratory-reared Pachón cavefish and Rio Choy surface fish of A. mexicanus across different tissues and ages. Results: Astyanax mexicanus surface fish exhibited longer average telomere length compared to cavefish. In addition, we did not observe telomere attrition in either cave or surface form as a result of aging in adults up to 9 years old, suggesting that efficient mechanisms prevent telomere-mediated senescence in laboratory stocks of this species, at least within this time frame. Our results suggest that telomere length in Astyanax may be considered a biomarker of environmental exposures. Cavefish may have evolved shorter and energetically less costly telomeres due to the absence of potential stressors known to affect surface species, such as predator pressure and ultra-violet radiation. This study provides the first insights into telomere dynamics in Astyanax morphs and suggests that shorter telomeres may have evolved as an adaptation to caves.


Assuntos
Cavernas , Telômero , Animais , Telômero/genética , Envelhecimento/genética , Exposição Ambiental , Biomarcadores
9.
PeerJ ; 12: e17017, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38436014

RESUMO

Background: The neurotoxic effects of lead in children can have long-lasting and profound impacts on the developing nervous system. This study aimed to identify a reliable and easily accessible biomarker to monitor neurological impairment in lead-poisoned children. Methods: We analyzed hematological data from 356 lead-poisoned children, comparing them with age and gender-matched healthy controls. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were employed to identify and evaluate potential biomarkers for neurological damage. Results: Significant changes in erythrocyte parameters were observed in lead-poisoned children. Upon further analysis, increased mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width-standard deviation (RDW-SD) interaction values were found to be significantly associated with neurological impairment. The MCHC*RDW-SD interaction model demonstrated an AUC of 0.76, indicating its effectiveness in reflecting neurological damage. Additionally, the MCHC*RDW-SD Interaction value showed weak or no correlation with other erythrocyte parameters, suggesting its independence as an indicator. Conclusion: Our findings propose the increased MCHC*RDW-SD interaction value as a robust and independent biomarker for detecting neurological impairment in lead-poisoned children. This underscores the potential of utilizing specific erythrocyte parameters for screening the neurotoxic effects of lead exposure in pediatric populations.


Assuntos
Intoxicação por Chumbo , Síndromes Neurotóxicas , Criança , Humanos , Índices de Eritrócitos , Intoxicação por Chumbo/diagnóstico , Curva ROC , Biomarcadores
10.
Eur Rev Med Pharmacol Sci ; 28(4): 1524-1540, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436186

RESUMO

The prevalence of both atrial fibrillation (AF) and diabetes is increasing day by day and commonly co-exist with a longer duration of diabetes and poor control, putting the individual at higher risk of AF. This review article presented some traditional and novel biomarkers related to AF in patients with diabetes mellitus. The literature review employed several databases, including Google Scholar, PubMed, and Science Direct. The investigation was finished on October 30, 2023. Many terms are utilized, including "AF", "Biomarkers", "Diabetes Mellitus", and "Pathogenesis". There are numerous biomarkers of diabetes, but this review article reports only leptin, adiponectin, glycated hemoglobin, ceramide, ferritin, fibrinogen, hematological indices, interleukin-18, thrombospondin 1, acylcarnitine, plasminogen activator inhibitor-1 and triglycerides and high-density lipoprotein cholesterol, since those biomarkers play a significant role in the pathogenesis of AF. However, no data was found, including fructosamine, glycated albumin, 1,5 anhydroglucitol, fetuin-A, α-hydroxybutyrate, mannose-binding lectin serine peptidase, transferrin, IL-1 receptor antagonist in AF. Understanding the interplay between diabetes and AF through the measurement of relevant biomarkers can contribute to better risk assessment, early detection, and the development of targeted therapeutic strategies for individuals at risk or already affected by these conditions.


Assuntos
Fibrilação Atrial , Diabetes Mellitus , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Adiponectina , Biomarcadores , Ceramidas
11.
Front Immunol ; 15: 1326026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426107

RESUMO

Background: For IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis. Methods: The study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells. Results: miRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis. Conclusion: Urinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.


Assuntos
Glomerulonefrite por IGA , MicroRNAs , Humanos , Glomerulonefrite por IGA/patologia , Biomarcadores/urina , Fibrose , MicroRNAs/metabolismo , Atrofia , Colágeno , Luciferases
12.
Methods Mol Biol ; 2785: 3-14, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427184

RESUMO

As our knowledge about the biology of Alzheimer's disease (AD) expands and we recognize the significance of early intervention for effective treatment, there is a shift in focus toward detecting the disease at an early stage. AD is characterized by the accumulation of misfolded amyloid-ß (Aß) and phosphorylated tau proteins in the brain, leading to the formation of senile plaques and neurofibrillary tangles. While a definitive diagnosis of AD can only be confirmed through autopsy by examining these pathological features, there are now reliable methods available for diagnosing the disease in living individuals. These methods involve analyzing cerebrospinal fluid and using positron emission tomography to accurately assess the presence of Aß and tau proteins. While these diagnostic markers have shown high accuracy in memory-clinic populations, they do have limitations such as the requirement for invasive lumbar puncture or exposure to ionizing radiation. Additionally, they are not easily accessible outside of specialized healthcare settings. Blood-based biomarkers of the core pathological features of AD are being developed, showing promise for less invasive, scalable identification of AD cases in the community. The advantages for the healthcare systems of this development are obvious, but the diagnostic performance of blood-based biomarkers in broader, non-selected populations outside of retrospective analyses and research cohorts still requires further investigation, including the combination with more effective neuropsychological assessments such as digital cognitive test solutions.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Estudos Retrospectivos , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano
13.
Methods Mol Biol ; 2785: 67-73, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427188

RESUMO

The therapeutic management of patients with Alzheimer's disease (AD) has been hindered by poor diagnostic accuracy. As such, there is an unmet clinical need for tools that can detect and diagnose the disease in its early stages. Compared with cerebrospinal fluid (CSF)-based biomarkers or positron emission tomography (PET), the use of reliable blood-based biomarkers could offer an accessible and minimally invasive method of streamlining diagnosis in the clinical setting. However, the influence of pre-analytical processing and sample handling parameters on the accurate measurement of protein biomarkers is well established, especially for AD CSF-based biomarkers. In this chapter, we provide recommendations for an optimal sample handling protocol for the analysis of blood-based biomarkers specifically for amyloid pathology in AD.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons/métodos , Biomarcadores/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano
14.
Methods Mol Biol ; 2785: 221-260, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427197

RESUMO

Recent research has revealed the potential of lipidomics and metabolomics in identifying new biomarkers and mechanistic insights for neurodegenerative disorders. To contribute to this promising area, we present a detailed protocol for conducting an integrated lipidomic and metabolomic profiling of brain tissue and biofluid samples. In this method, a single-phase methanol extraction is employed for extracting both nonpolar and highly polar lipids and metabolites from each biological sample. The extracted samples are then subjected to liquid chromatography-mass spectrometry-based assays to provide relative or semiquantitative measurements for hundreds of selected lipids and metabolites per sample. This high-throughput approach enables the generation of new hypotheses regarding the mechanistic and functional significance of lipid and metabolite alterations in neurodegenerative disorders while also facilitating the discovery of new biomarkers to support drug development.


Assuntos
Lipidômica , Doenças Neurodegenerativas , Humanos , Cromatografia Líquida/métodos , Lipídeos , Metabolômica/métodos , Biomarcadores/metabolismo , Encéfalo/metabolismo
15.
Methods Mol Biol ; 2785: 143-162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427193

RESUMO

Among others, the existence of pathophysiological biomarkers such as cerebrospinal fluid (CSF) Aß-42, t-tau, and p-tau preceding the onset of Alzheimer's disease (AD) symptomatology has shifted the conceptualization of AD as a continuum. In addition, magnetic resonance imaging (MRI) enables the study of structural and functional cross-sectional correlates and longitudinal changes in vivo, and therefore, the combination of CSF data and imaging analyses emerges as a synergistic approach to understand the structural correlates related with specific AD-related biomarkers. In this chapter, we describe the methods used in neuroimaging that will allow researchers to combine data on CSF metabolites with imaging analyses.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Estudos Transversais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/líquido cefalorraquidiano , Imageamento por Ressonância Magnética/métodos , Neuroimagem , Biomarcadores/líquido cefalorraquidiano
16.
Methods Mol Biol ; 2785: 115-142, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427192

RESUMO

MRS is a noninvasive technique to measure different metabolites in the brain. Changes in the levels of certain metabolites can be used as surrogate markers for Alzheimer's disease. They can potentially be used for diagnosis, prediction of prognosis, or even assessing response to treatment.There are different techniques for MRS acquisitions including STimulated Echo Acquisition Mode (STEAM) and Point Resolved Spectroscopy (PRESS). In terms of localization, single or multi-voxel methods can be used. Based on current data: 1. NAA, marker of neuronal integrity and viability, reduces in AD with longitudinal changes over the time as the disease progresses. There are data claiming that reduction of NAA is associated with tau accumulation, early neurodegenerative processes, and cognitive decline. Therefore, it can be used as a stage biomarker for AD to assess the severity of the disease. With advancement of disease modifying therapies, there is a potential role for NAA in the future to be used as a marker of response to treatment. 2. mI, marker of glial cell proliferation and activation, is associated with AB pathology and has early changes in the course of the disease. The NAA/mI ratio can be predictive of AD development with high specificity and can be utilized in the clinical setting to stratify cases for further evaluation with PET for potential treatments. 3. The changes in the level of other metabolites such as Chol, Glu, Gln, and GABA are controversial because of the lack of standardization of MRS techniques, current technical limitations, and possible region specific changes. 4. Ultrahigh field MRS and more advanced techniques can overcome many of these limitations and enable us to measure more metabolites with higher accuracy. 5. Standardization of MRS techniques, validation of metabolites' changes against PET using PET-guided technique, and longitudinal follow-ups to investigate the temporal changes of the metabolites in relation to other biomarkers and cognition will be crucial to confirm the utility of MRS as a potential noninvasive biomarker for AD.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Espectroscopia de Ressonância Magnética , Encéfalo/metabolismo , Cognição , Biomarcadores/metabolismo
17.
Methods Mol Biol ; 2785: 299-309, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427201

RESUMO

Digital biomarkers are of growing interest in the field of Alzheimer's Disease (AD) research. Digital biomarker data arising from digital health tools holds various potential benefits: more objective and more accurate assessment of patients' symptoms and remote collection of signals in real-world scenarios but also multimodal variance for prediction models of individual disease progression. Speech can be collected at minimal patient burden and provides rich data for assessing multiple aspects of AD pathology including cognition. However, the operations around collecting, preparing, and validly interpreting speech data within the context of clinical research on AD remains complex and sometimes challenging. Through a dedicated pipeline of speech collection tools, preprocessing steps and algorithms, precise qualification and quantification of an AD patient's pathology can be achieved from their speech. The aim of this chapter is to describe the methods that are needed to create speech collection scenarios that result in valuable speech-based digital biomarkers for clinical research.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Fala , Biomarcadores , Cognição , Progressão da Doença
18.
Methods Mol Biol ; 2785: 195-218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427196

RESUMO

The recent progress in the development of in vivo biomarkers is rapidly changing how neurodegenerative diseases are conceptualized and diagnosed and how clinical trials are designed today. Alzheimer's disease (AD) - the most common neurodegenerative disorder - is characterized by a complex neuropathology involving the deposition of extracellular amyloid-ß (Aß) plaques and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau proteins, accompanied by the activation of glial cells, i.e., astrocytes and microglia, and neuroinflammatory response, leading to neurodegeneration and cognitive dysfunction. An increasing diversity of positron emission tomography (PET) imaging radiotracers is available to selectively target the different pathophysiological processes of AD. Along with the success of Aß PET and the more recent tau PET imaging, there is a great interest to develop PET tracers to image glial reactivity and neuroinflammation. While most research to date has focused on imaging microgliosis, there is an upsurge of interest in imaging reactive astrocytes in the AD continuum. There is increasing evidence that reactive astrocytes are morphologically and functionally heterogeneous, with different subtypes that express different markers and display various homeostatic or detrimental roles across disease stages. Therefore, multiple biomarkers are desirable to unravel the complex phenomenon of reactive astrocytosis. In the field of in vivo PET imaging in AD, the research concerning reactive astrocytes has predominantly focused on targeting monoamine oxidase B (MAO-B), most often using either 11C-deuterium-L-deprenyl (11C-DED) or 18F-SMBT-1 PET tracers. Additionally, imidazoline2 binding (I2BS) sites have been imaged using 11C-BU99008 PET. Recent studies in our group using 11C-DED PET imaging suggest that astrocytosis may be present from the early stages of disease development in AD. This chapter provides a detailed description of the practical approach used for the analysis of 11C-DED PET imaging data in a multitracer PET paradigm including 11C-Pittsburgh compound B (11C-PiB) and 18F-fluorodeoxyglucose (18F-FDG). The multitracer PET approach allows investigating the comparative regional and temporal patterns of in vivo brain astrocytosis, fibrillar Aß deposition, glucose metabolism, and brain structural changes. It may also contribute to understanding the potential role of novel plasma biomarkers of reactive astrocytes, in particular the glial fibrillary acidic protein (GFAP), at different stages of disease progression. This chapter attempts to stimulate further research in the field, including the development of novel PET tracers that may allow visualizing different aspects of the complex astrocytic and microglial response in neurodegenerative diseases. Progress in the field will contribute to the incorporation of PET imaging of glial reactivity and neuroinflammation as biomarkers with clinical application and motivate further investigation on glial cells as therapeutic targets in AD and other neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Gliose , Humanos , Gliose/metabolismo , Doenças Neuroinflamatórias , Doença de Alzheimer/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Fluordesoxiglucose F18/metabolismo , Inflamação/metabolismo , Placa Amiloide/metabolismo , Biomarcadores/metabolismo
19.
Methods Mol Biol ; 2785: 311-320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427202

RESUMO

Cognitive testing is an essential part of clinical diagnostics and clinical trials in Alzheimer's disease. Digital cognitive tests hold a great opportunity to provide more versatile and cost-efficient patient pathways through flexible testing including at home. In this work, we describe a web-based cognitive test, cCOG, that can be used in screening, differential diagnosis, and monitoring the progression of neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Disfunção Cognitiva/diagnóstico , Doença de Alzheimer/diagnóstico , Diagnóstico Diferencial , Cognição , Internet , Biomarcadores , Progressão da Doença
20.
Methods Mol Biol ; 2785: 321-344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427203

RESUMO

Biological validation of preliminary findings is a key prerequisite in biomarker discovery. In recent years, the development of advanced large-scale sequencing technologies combined with high-throughput computational analysis methods led to the extraction of considerable amount of data from healthy and diseased tissues. Stored in large open-access repositories, these data can be accessed and interrogated by researchers aiming at understanding the biological rationale behind their results. These so called in silico analyses, in opposite to in vitro analyses, have gained increasing importance in recent years, becoming a major component of research projects and publications. However, making sense of the large amount of data available can be challenging and may lead to a misinterpretation of the data. To reduce the dimensionality of this data, recent years have seen the development of statistical m\ethods and advanced graph analytics which help researchers summarize the available data and draw appropriate conclusions. In this chapter we will describe three in silico methods to investigate the biological underpinnings of a panel of seven blood-based biomarkers of Alzheimer's disease.


Assuntos
Doença de Alzheimer , Pesquisa Biomédica , Humanos , Doença de Alzheimer/diagnóstico , Biomarcadores , Nível de Saúde , Simulação por Computador
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