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1.
Food Chem ; 462: 140961, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39208724

RESUMEN

The underlying toxicity mechanisms of microplastics on oysters have rarely been explored. To fill this gap, the present study investigated the metabolic profile and protein expression responses of oysters to microplastic stress through metabolomics and biochemical analyses. Oysters were exposed to microplastics for 21 days, and the results indicated that the microplastics induced oxidative stress, with a significant decrease in SOD activity in the 0.1 mg/L exposure group. Metabolomics revealed that exposure to microplastics disturbed many metabolic pathways, such as amino acid metabolism, lipid metabolism, biosynthesis of amino acids, aminoacyl-tRNA biosynthesis, and that different concentrations of microplastics induced diverse metabolomic profiles in oysters. Overall, the current study provides new reference data and insights for assessing food safety and consumer health risks caused by microplastic contamination.


Asunto(s)
Crassostrea , Microplásticos , Estrés Oxidativo , Poliestirenos , Contaminantes Químicos del Agua , Animales , Crassostrea/metabolismo , Crassostrea/efectos de los fármacos , Crassostrea/química , Microplásticos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Estrés Oxidativo/efectos de los fármacos , Poliestirenos/química , Poliestirenos/metabolismo , Metaboloma/efectos de los fármacos , Mariscos/análisis , Metabolómica , Contaminación de Alimentos/análisis
2.
Food Chem ; 462: 140943, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39217744

RESUMEN

Application of microbial-based biopreparations as a pre-harvest strategy offers a method to obtain sustainable agricultural practices and could be an important approach for advancing food science, promoting sustainability, and meeting global food market demands. The impact of a bacterial-fungal biopreparation mixture on soil-plant-microbe interactions, fruit chemical composition and yield of 7 raspberry clones was investigated by examining the structural and functional profiles of microbial communities within leaves, fruits, and soil. Biopreparation addition caused the enhancement of the microbiological utilization of specific compounds, such as d-mannitol, relevant in plant-pathogen interactions and overall plant health. The biopreparation treatment positively affected the nitrogen availability in soil (9-160%). The analysis of plant stress marker enzymes combined with the evaluation of fruit quality and chemical properties highlight changes inducted by the pre-harvest biopreparation application. Chemical analyses highlight biopreparations' role in soil and fruit quality improvement, promoting sustainable agriculture. This effect was dependent on tested clones, showing increase of soluble solid content in fruits, concentration of polyphenols or the sensory quality of the fruits. The results of the next-generation sequencing indicated increase in the effective number of bacterial species after biopreparation treatment. The network analysis showed stimulating effect of biopreparation on microbial communities by enhancing microbial interactions (increasing the number of network edges up to 260%) of and affecting the proportions of mutual relationships between both bacteria and fungi. These findings show the potential of microbial-based biopreparation in enhancing raspberry production whilst promoting sustainable practices and maintaining environmental homeostasis and giving inshght in holistic understanding of microbial-based approaches for advancing food science monitoring.


Asunto(s)
Bacterias , Frutas , Hongos , Rubus , Microbiología del Suelo , Suelo , Frutas/química , Frutas/microbiología , Frutas/metabolismo , Rubus/química , Rubus/microbiología , Rubus/metabolismo , Rubus/crecimiento & desarrollo , Suelo/química , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/crecimiento & desarrollo , Hongos/metabolismo , Hongos/crecimiento & desarrollo , Agricultura , Microbiota
3.
Clin Chim Acta ; 564: 119925, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39151672

RESUMEN

BACKGROUND: In pediatric cardiology, the fact that some new biomarkers have assay-specific normal values has to be considered for correct clinical decisions. The current study aimed to provide age-adjusted normative values for NT-proBNP and Galectin-3 using the Abbott immunoassay system from a prospective French pediatric cohort sera collection and to validate our data for NT-proBNP on a second retrospective cohort. METHODS: We analyzed 283 consecutive samples for NT-proBNP and 140 samples for Galectin-3 collected from apparently healthy children (0-18 years) with outpatient treatment at our institution (Hôpital Necker-Enfants malades, Paris, France) during 24 months. RESULTS: For NT-proBNP and Galectin-3, we establish four age partitions, respectively two (<2 years / >2 years) and establish upper reference values and their 90 % CI for each biomarker (Galectin-3 (ng/mL): 56 [44-70] / 26 [23-29]). We evaluated the diagnostic performance of our upper reference values of NT-proBNP on a retrospective cohort (n = 428) with positive predictive value of 0.92. CONCLUSIONS: Using Abbott immunoassay system, we report age-specific reference values for NT-proBNP and for the first time for Galectin-3 in a healthy French pediatric cohort. These data call for larger cohort studies to define more robustly percentiles and diagnostic performance for NT-proBNP.


Asunto(s)
Galectina 3 , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Humanos , Niño , Fragmentos de Péptidos/sangre , Adolescente , Preescolar , Lactante , Francia , Valores de Referencia , Péptido Natriurético Encefálico/sangre , Femenino , Galectina 3/sangre , Estudios de Cohortes , Masculino , Recién Nacido , Inmunoensayo/normas , Biomarcadores/sangre , Estudios Retrospectivos , Galectinas/sangre
4.
Noncoding RNA Res ; 10: 41-54, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39296638

RESUMEN

In the search for new biomarkers and therapeutic targets for infectious diseases, several molecules have been investigated. Small RNAs, known as microRNAs (miRs), are important regulators of gene expression, and have emerged as promising candidates for these purposes. MiRs are a class of small, endogenous non-coding RNAs that play critical roles in several human diseases, including host-pathogen interaction mechanisms. Recently, miRs signatures have been reported in different infectious diseases, opening new perspectives for molecular diagnosis and therapy. MiR profiles can discriminate between healthy individuals and patients, as well as distinguish different disease stages. Furthermore, the possibility of assessing miRs in biological fluids, such as serum and whole blood, renders these molecules feasible for the development of new non-invasive diagnostic and prognostic tools. In this manuscript, we will comprehensively describe miRs as biomarkers and therapeutic targets in infectious diseases and explore how they can contribute to the advance of existing and new tools. Additionally, we will discuss different miR analysis platforms to understand the obstacles and advances of this molecular approach and propose their potential clinical applications and contributions to public health.

5.
J Environ Sci (China) ; 147: 165-178, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003037

RESUMEN

In this study, two wheat-derived cadmium (Cd)-immobilizing endophytic Pseudomonas paralactis M14 and Priestia megaterium R27 were evaluated for their effects on wheat tissue Cd uptake under hydroponic conditions. Then, the impacts of the biochar (BC), M14+R27 (MR), and BC+MR treatments on wheat Cd uptake and the mechanisms involved were investigated at the jointing, heading, and mature stages of wheat plants under field-plot conditions. A hydroponic experiment showed that the MR treatment significantly decreased the above-ground tissue Cd content compared with the M14 or R27 treatment. The BC+MR treatment reduced the grain Cd content by 51.5%-67.7% and Cd translocation factor at the mature stage of wheat plants and increased the organic matter-bound Cd content by 31%-75% in the rhizosphere soils compared with the BC or MR treatment. Compared with the BC or MR treatment, the relative abundances of the biomarkers associated with Gemmatimonas, Altererythrobacter, Gammaproteobacteria, Xanthomonadaceae, Phenylobacterium, and Nocardioides in the BC+MR-treated rhizosphere microbiome decreased and negatively correlated with the organic matter-bound Cd contents. In the BC+MR-treated root interior microbiome, the relative abundance of the biomarker belonging to Exiguobacterium increased and negatively correlated with the Cd translocation factor, while the relative abundance of the biomarker belonging to Pseudonocardiaceae decreased and positively correlated with the Cd translocation factor. Our findings suggested that the BC+MR treatment reduced Cd availability and Cd transfer through affecting the abundances of these specific biomarkers in the rhizosphere soil and root interior microbiomes, leading to decreased wheat grain Cd uptake in the contaminated soil.


Asunto(s)
Cadmio , Carbón Orgánico , Microbiología del Suelo , Contaminantes del Suelo , Triticum , Triticum/metabolismo , Triticum/microbiología , Cadmio/metabolismo , Contaminantes del Suelo/metabolismo , Endófitos/fisiología , Rizosfera , Suelo/química , Biodegradación Ambiental , Microbiota/efectos de los fármacos
6.
Methods Mol Biol ; 2852: 47-64, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39235736

RESUMEN

Electrochemical approaches, along with miniaturization of electrodes, are increasingly being employed to detect and quantify nucleic acid biomarkers. Miniaturization of the electrodes is achieved through the use of screen-printed electrodes (SPEs), which consist of one to a few dozen sets of electrodes, or by utilizing printed circuit boards. Electrode materials used in SPEs include glassy carbon (Chiang H-C, Wang Y, Zhang Q, Levon K, Biosensors (Basel) 9:2-11, 2019), platinum, carbon, and graphene (Cheng FF, He TT, Miao HT, Shi JJ, Jiang LP, Zhu JJ, ACS Appl Mater Interfaces 7:2979-2985, 2015). There are numerous modifications to the electrode surfaces as well (Cheng FF, He TT, Miao HT, Shi JJ, Jiang LP, Zhu JJ, ACS Appl Mater Interfaces 7:2979-2985, 2015). These approaches offer distinct advantages, primarily due to their demonstrated superior limit of detection without amplification. Using the SPEs and potentiostats, we can detect cells, proteins, DNA, and RNA concentrations in the nanomolar (nM) to attomolar (aM) range. The focus of this chapter is to describe the basic approach adopted for the use of SPEs for nucleic acid measurement.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Electrodos , Grafito , Grafito/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Ácidos Nucleicos/análisis , Humanos , ADN/análisis
7.
Clin Chim Acta ; 564: 119937, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39173701

RESUMEN

BACKGROUND: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. OBJECTIVE: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. METHODS: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. RESULTS: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. CONCLUSION: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.


Asunto(s)
Enfermedades Cardiovasculares , Glicopéptidos , Fallo Renal Crónico , Diálisis Renal , Humanos , Glicopéptidos/sangre , Diálisis Renal/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/diagnóstico , Fallo Renal Crónico/terapia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Anciano , Biomarcadores/sangre
8.
Clin Chim Acta ; 564: 119941, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39181294

RESUMEN

BACKGROUND: In Alzheimer's disease (AD) diagnosis, a cerebrospinal fluid (CSF) biomarker panel is commonly interpreted with binary cutoff values. However, these values are not generic and do not reflect the disease continuum. We explored the use of interval-specific likelihood ratios (LRs) and probability-based models for AD using a CSF biomarker panel. METHODS: CSF biomarker (Aß1-42, tTau and pTau181) data for both a clinical discovery cohort of 241 patients (measured with INNOTEST) and a clinical validation cohort of 129 patients (measured with EUROIMMUN), both including AD and non-AD dementia/cognitive complaints were retrospectively retrieved in a single-center study. Interval-specific LRs for AD were calculated and validated for univariate and combined (Aß1-42/tTau and pTau181) biomarkers, and a continuous bivariate probability-based model for AD, plotting Aß1-42/tTau versus pTau181 was constructed and validated. RESULTS: LR for AD increased as individual CSF biomarker values deviated from normal. Interval-specific LRs of a combined biomarker model showed that once one biomarker became abnormal, LRs increased even further when another biomarker largely deviated from normal, as replicated in the validation cohort. A bivariate probability-based model predicted AD with a validated accuracy of 88% on a continuous scale. CONCLUSIONS: Interval-specific LRs in a combined biomarker model and prediction of AD using a continuous bivariate biomarker probability-based model, offer a more meaningful interpretation of CSF AD biomarkers on a (semi-)continuous scale with respect to the post-test probability of AD across different assays and cohorts.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Probabilidad , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Humanos , Biomarcadores/líquido cefalorraquídeo , Femenino , Masculino , Anciano , Péptidos beta-Amiloides/líquido cefalorraquídeo , Funciones de Verosimilitud , Persona de Mediana Edad , Proteínas tau/líquido cefalorraquídeo , Estudios Retrospectivos , Fragmentos de Péptidos/líquido cefalorraquídeo , Estudios de Cohortes
9.
Open Forum Infect Dis ; 11(9): ofae469, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39233711

RESUMEN

Background: Fostemsavir, a first-in-class attachment inhibitor that binds to the viral envelope protein gp120, is approved for heavily treatment-experienced persons with HIV-1 with limited treatment options. We explored changes in immunologic and coagulopathy parameters in the BRIGHTE study: a phase 3 trial that evaluated fostemsavir plus optimized background therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1. Methods: CD4+ T-cell count, CD4+/CD8+ ratio, soluble CD14, soluble CD163, and D-dimer levels were measured through 96 weeks in participants with 1 or 2 fully active antiretroviral agents available at screening. No formal statistical analyses were performed. Results: Among 272 participants, increases were observed from baseline to week 96 in CD4+ T-cell count (mean increase, +205 cells/mm3) and CD4+/CD8+ ratio (mean increase, +0.24). The proportion of observed participants with a CD4+/CD8+ ratio ≥0.45 increased from 9% (25/272) at baseline to 40% (85/213) at week 96. From baseline to week 96, we also observed trends toward decreases in the following (mean [SD] change): soluble CD14, -738.2 (981.8) µg/L; soluble CD163, -138.0 (193.4) µg/L; and D-dimer, -0.099 (0.521) mg/L fibrinogen-equivalent units. Decreases in biomarkers were generally observed among subgroups by baseline disease characteristics, virologic response, and CD4+ T-cell count. Conclusions: These data suggest that heavily treatment-experienced persons with multidrug-resistant HIV-1 treated with fostemsavir + optimized background therapy may have improvements in immune parameters, including markers of monocyte activation and coagulopathy. Clinical Trials Registration: NCT02362503 (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT02362503).

10.
MethodsX ; 13: 102897, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39233753

RESUMEN

We present a review of the latest framework achievements in geoarchaeological sciences applied to microstratigraphic and biomolecular studies of prehistoric archaeological contexts, highlighting the importance of musealized archaeological stratigraphies. We assess how today's scientific and technological accomplishments can be tailored for archaeological human ecology studies with analytical ensembles that provide unprecedented results. Sampling and processing workflows originating from resin consolidation and thin section micromorphology of undisturbed blocks of archaeological soils and sediments, guarantee subsampling accuracy at the micrometre scale granting access to individual components otherwise impossible to target: the achievable information yield makes even the smallest soil samples potential sources of pioneering discoveries. Yet, archaeological excavations are still the primary mode of retrieving new soil samples. We argue that, when dealing with archaeological sites that were excavated and partially musealised in the past, the exploration of related museum collections should be prioritized as perspective source of new study samples. Analysing old and potentially very informative samples, with an approach that we define as "Green Archaeology", may represent a source of well-structured primary data as well as a means for planning new excavations, delivering novel discoveries while safeguarding site integrity and promoting Third Mission valorisation of sites and heritage dormant collections.

11.
Front Pediatr ; 12: 1432113, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39233870

RESUMEN

Background: Gestational diabetes mellitus (GDM) significantly affects the fetal metabolic environment, elevating risks of neonatal hypoglycemia and macrosomia. Metabolomics offers promising avenues for early prediction and diagnosis of GDM and associated adverse offspring outcomes. Methods: This study analyzed serum samples from pregnant women diagnosed with GDM at 24 to 28 weeks of gestation using untargeted metabolomics. We monitored the health outcomes of their offspring to explore the correlation between initial serum metabolite profiles and subsequent health outcomes, to uncover the predictive markers for hypoglycemia and macrosomia in these offspring. Results: Out of 200 participants, 154 had normal newborns, 33 had offspring with hypoglycemia, and 19 had offspring with macrosomia. From 448 identified metabolites, 66 showed significant differences in cases of hypoglycemia, and 45 in macrosomia. A panel of serum metabolite biomarkers achieved Area Under the Curve (AUC) values of 0.8712 for predicting hypoglycemia and 0.9434 for macrosomia. Conclusion: The study delineated metabolic disruptions in GDM during 24-28 weeks of gestation and pinpointed biomarkers capable of forecasting adverse neonatal outcomes. These findings could inform GDM management strategies and minimize the incidence of such outcomes.

12.
Cureus ; 16(8): e66205, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39233932

RESUMEN

Gallbladder carcinoma (GBC) presents a significant clinical challenge due to its aggressive nature and often asymptomatic progression, resulting in late-stage diagnoses and a poor prognosis. Early detection and accurate staging are pivotal for improving patient outcomes, highlighting the critical role of advanced imaging techniques in oncological practice. Magnetic resonance spectroscopy (MRS) has emerged as a valuable non-invasive tool capable of assessing biochemical changes within tissues, including alterations in choline metabolism-a biomarker indicative of cell membrane turnover and proliferation. This review explores the application of MRS in evaluating choline levels in gallbladder carcinoma, synthesizing current literature to elucidate its potential in clinical settings. By analyzing studies investigating the correlation between choline levels detected via MRS and tumor characteristics, this review underscores MRS's role in enhancing diagnostic precision and guiding therapeutic decision-making. Moreover, it discusses the challenges and limitations associated with MRS in clinical practice alongside future research and technological advancement directions. Ultimately, integrating MRS into the diagnostic armamentarium for gallbladder carcinoma promises to improve early detection and treatment outcomes. This review provides insights into the evolving landscape of MRS in oncology, emphasizing its contribution to personalized medicine approaches aimed at optimizing patient care and management strategies for GBC.

13.
Natl J Maxillofac Surg ; 15(2): 177-182, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234125

RESUMEN

To review the literature on the effect of mandibular advancement therapy (MAT) on inflammatory biomarkers in obstructive sleep apnea (OSA). The present systematic review addresses the following focus question: What is the effect of MAT on inflammatory biomarkers in OSA? Electronic and manual literature searches were conducted on databases: PubMed/MEDLINE, Web of Science, and Cochrane Library for studies published until September 2021 to collect information about the effect of mandibular advancement therapy, a non-continuous positive airway pressure alternative measurement of OSA. A systematic literature review was performed following the PRISMA guidelines to identify studies evaluating the effect of MAT in patients suffering from OSA. Randomized clinical trials were included, and case reports, retrospective studies, literature reviews, in-vitro studies, observational studies, authors' opinions, letters to the editor, and engineering articles were excluded. Fifty-nine articles published before September 2021 were identified. Fifty-four articles met the inclusion criteria. After assessing inclusion criteria, three clinical trials were included with 148 patients suffering from OSA and treated with mandibular advancement therapy. The follow-up period ranged from two to three months, with the average follow-up being 1.66 months. The mean age of the patients was observed to be 53.11 ± 2.65 years. The mean Epworth Sleepiness Scale observed in patients in all three clinical trials was 9.75 ± 0.89. MAT in patients with moderate or severe OSA reduced apnea-hypopnea index but has less effect on inflammatory and metabolic biomarkers.

14.
Front Immunol ; 15: 1438838, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234237

RESUMEN

Background: The purpose of this study is to investigate the causal effect and potential mechanisms between telomere length and abdominal aortic aneurysm (AAA). Methods: Summary statistics of telomere length and AAA were derived from IEU open genome-wide association studies and FinnGen R9, respectively. Bi-directional Mendelian randomization (MR) analysis was conducted to reveal the causal relationship between AAA and telomere length. Three transcriptome datasets were retrieved from the Gene Expression Omnibus database and telomere related genes was down-loaded from TelNet. The overlapping genes of AAA related differentially expressed genes (DEGs), module genes, and telomere related genes were used for further investigation. Telomere related diagnostic biomarkers of AAA were selected with machine learning algorisms and validated in datasets and murine AAA model. The correlation between biomarkers and immune infiltration landscape was established. Results: Telomere length was found to have a suggestive negative associations with AAA [IVW, OR 95%CI = 0.558 (0.317-0.701), P < 0.0001], while AAA showed no suggestive effect on telomere length [IVW, OR 95%CI = 0.997 (0.990-1.004), P = 0.4061]. A total of 40 genes was considered as telomere related DEGs of AAA. PLCH2, PRKCQ, and SMG1 were selected as biomarkers after multiple algorithms and validation. Immune infiltration analysis and single cell mRNA analysis revealed that PLCH2 and PRKCQ were mainly expressed on T cells, while SMG1 predominantly expressed on T cells, B cells, and monocytes. Murine AAA model experiments further validated the elevated expression of biomarkers. Conclusion: We found a suggestive effect of telomere length on AAA and revealed the potential biomarkers and immune mechanism of telomere length on AAA. This may shed new light for diagnosis and therapeutics on AAA.


Asunto(s)
Aneurisma de la Aorta Abdominal , Estudio de Asociación del Genoma Completo , Homeostasis del Telómero , Telómero , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/inmunología , Animales , Ratones , Humanos , Telómero/genética , Análisis de la Aleatorización Mendeliana , Biomarcadores , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Transcriptoma , Predisposición Genética a la Enfermedad
15.
Front Immunol ; 15: 1351584, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234243

RESUMEN

Over the last decade, a new paradigm for cancer therapies has emerged which leverages the immune system to act against the tumor. The novel mechanism of action of these immunotherapies has also introduced new challenges to drug development. Biomarkers play a key role in several areas of early clinical development of immunotherapies including the demonstration of mechanism of action, dose finding and dose optimization, mitigation and prevention of adverse reactions, and patient enrichment and indication prioritization. We discuss statistical principles and methods for establishing the prognostic, predictive aspect of a (set of) biomarker and for linking the change in biomarkers to clinical efficacy in the context of early development studies. The methods discussed are meant to avoid bias and produce robust and reproducible conclusions. This review is targeted to drug developers and data scientists interested in the strategic usage and analysis of biomarkers in the context of immunotherapies.


Asunto(s)
Biomarcadores de Tumor , Inmunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Inmunoterapia/métodos , Desarrollo de Medicamentos , Animales
16.
Front Immunol ; 15: 1421036, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234258

RESUMEN

Extracellular vesicles (EVs) are heterogeneous, phospholipid membrane enclosed particles that are secreted by healthy and cancerous cells. EVs are present in diverse biological fluids and have been associated with the severity of diseases, which indicates their potential as biomarkers for diagnosis, prognosis and as therapeutic targets. This study investigated the phenotypic characteristics of EVs derived from peripheral blood (PB) and bone marrow (BM) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) during different treatment stages. PB and BM plasma were collected from 20 B-ALL patients at three time points during induction therapy, referred to as: diagnosis baseline (D0), day 15 of induction therapy (D15) and the end of the induction therapy (D35). In addition, PB samples were collected from 10 healthy children at a single time point. The EVs were measured using CytoFLEX S flow cytometer. Calibration beads were employed to ensure accurate size analysis. The following, fluorescent-labeled specific cellular markers were used to label the EVs: Annexin V (phosphatidylserine), CD235a (erythrocyte), CD41a (platelet), CD51 (endothelial cell), CD45 (leukocyte), CD66b (neutrophil), CD14 (monocyte), CD3 (T lymphocyte), CD19, CD34 and CD10 (B lymphoblast/leukemic blast). Our results demonstrate that B-ALL patients had a marked production of EV-CD51/61+, EV-CD10+, EV-CD19+ and EV-CD10+CD19+ (double-positive) with a decrease in EV-CD41a+ on D0. However, the kinetics and signature of production during induction therapy revealed a clear decline in EV-CD10+ and EV-CD19+, with an increase of EV-CD41a+ on D35. Furthermore, B-ALL patients showed a complex biological network, exhibiting distinct profiles on D0 and D35. Interestingly, fold change and ROC curve analysis demonstrated that EV-CD10+CD19+ were associated with B-ALL patients, exhibited excellent clinical performance and standing out as a potential diagnostic biomarker. In conclusion, our data indicate that EVs represent a promising field of investigation in B-ALL, offering the possibility of identifying potential biomarkers and therapeutic targets.


Asunto(s)
Médula Ósea , Vesículas Extracelulares , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Niño , Vesículas Extracelulares/metabolismo , Femenino , Masculino , Preescolar , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Médula Ósea/metabolismo , Adolescente , Prueba de Estudio Conceptual , Biomarcadores de Tumor , Lactante
17.
Med Pharm Rep ; 97(3): 298-307, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39234458

RESUMEN

Background and aim: Lung cancer remains one of the most threatening malignancies, ranking as the second most diagnosed cancer, and it continues to be the leading cause of cancer-related deaths worldwide. Challenges persist with late diagnosis and the high mutational burden characteristic of lung cancer. Methods: Our study focuses on identifying the mutational spectrum of a cohort of advanced-stage non-small cell lung cancer (NSCLC) patients using a minimally invasive method through blood collection. To analyze the mutational landscape of these patients, we employed plasma DNA for the next-generation sequencing (NGS) cancer panel Ion Torrent, which contains 50 of the most mutated genes in lung cancer. All protocols for extraction, quality and quantity control, and library preparation follow the manufacturer's rules. Bioinformatics analysis was performed to select pathogenic mutations versus non-pathogenic-benign ones. Results: This approach is particularly valuable for patients in advanced stages (III and IV, n=10) of lung adenocarcinoma and lung squamous cell carcinoma, who lack surgical options and limited therapeutic avenues. The comprehensive sequencing analysis revealed that nine of the ten lung cancer patients carried a TP53 mutation. Also, several other mutations exist in various cases, showing heterogeneous profiling. Conclusions: Our findings demonstrate the potential of liquid biopsies in providing crucial genetic insights that can guide personalized treatment strategies, improving the management and outcomes for patients with advanced lung cancer.

18.
Front Mol Biosci ; 11: 1448946, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234569

RESUMEN

Background: Cytokine network disturbances in primary Sjögren's syndrome (pSS) have been reported in many studies. However, their functions in patients with primary Sjögren's syndrome and interstitial lung disease (pSS-ILD) is controversial. In this study, we aim to investigate the associations of immunological characteristics and cytokine profiles with pSS-ILD pathogenesis and explore their predictive values for pSS progression. Methods: A total of 256 patients initially diagnosed with pSS at Henan Provincial People's Hospital were enrolled. After excluding the patients previously diagnosed with various serious acute and chronic respiratory system diseases and cases with other connective tissue diseases or congenital heart diseases, 94 pSS patients were included for further analysis, including 40 patients with ILD (pSS-ILD) and 54 patients without ILD (pSS-N-ILD). For comparison, 41 age- and sex-matched healthy individuals were included as normal controls. Their clinical symptoms and serological data including cyclic citrullinated peptide (CCP) antibody (anti-CCP), antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB, C-reactive protein, IgG, IgM, IgA, C3, C4, and 10 cytokines and chemokines were obtained. Wilcoxon test, chi-square test, Spearman correlation analysis, and logistics regression analysis were performed. Results: Higher positive rates of anti-SSB and higher incidence of dry cough, dyspnea, and arthrosis symptoms were shown in pSS-ILD patients than in the pSS-N-ILD cases. Anti-CCP antibodies and cytokines (IL-1ß, TNFα, IL-6, IL-5, IL-12p70, and IL-17) were higher, while C3 was lower in pSS-ILD patients than in pSS-N-ILD cases. Significant negative correlations of IgG with C3 and C4 and positive correlations of IL-12p70 and IL-17 with IL-6 were only shown in pSS-ILD patients. The anti-CCP antibody was positively correlated with IL-5 in pSS-ILD patients, but not in pSS-N-ILD cases. Multi-variable logistics regression analysis revealed the combination of anti-CCP, IL-17, IL-12p70, and IL-5 was effective in predicting the status of pSS-ILD in the pSS cases. Conclusion: There were significant differences in serum marker levels between pSS-ILD and pSS-N-ILD cases. The combination of anti-CCP, IL-17, IL-12p70, and IL-5 might be a potential risk predictor for pSS-ILD occurrence. The cytokines might be involved in the development and progression of pSS-ILD. These results would provide new therapeutic targets for pSS-ILD treatment.

19.
Periodontol 2000 ; 95(1): 7-9, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39235922

RESUMEN

Chronic inflammatory periodontal disease and its related condition, peri-implant disease, are highly prevalent globally and require accurate and speedy diagnosis. The focus of this volume dedicated to diagnostics is to cover modern enhancements in accuracy, simplicity and speed. An international assortment of experts has been tasked with reviewing defined areas of current best practice as well innovation in the field of periodontitis and peri-implantitis diagnostics. Periodontitis and peri-implantitis are irreversible, chronic, cumulative conditions propagated by bacteria and host factors, which involve soft and hard tissue changes, and these changes are measured in the diagnostic process. Clinically relevant modifications to the healthy state are detected using clinical, radiological and laboratory or point of care testing, and these testing approaches are critically reviewed at length in this state-of-the-art resume of periodontal diagnostics.


Asunto(s)
Periimplantitis , Humanos , Implantes Dentales , Periimplantitis/diagnóstico , Periimplantitis/microbiología , Periodoncia/instrumentación , Periodontitis/diagnóstico , Periodontitis/microbiología
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