RESUMEN
Early and rapid diagnostic of acute myocardial infarction (AMI) during its developing stage is crucial due to its high fatality rate. Heart-type fatty acid binding protein (h-FABP) is an ideal biomarker for the quantitative diagnosis of AMI, surpassing traditional markers such as myoglobin, creatine phosphokinase-MB, and troponin in terms of sensitivity, specificity, and prognostic value. To obtain diagnostic and prognostic information, a precise and fully quantitative measurement of h-FABP is essential, typically achieved through an immunosorbent assay like the enzyme-linked immunosorbent assay. Nevertheless, this method has several limitations, including extended detection time, complex assay procedures, the necessity for skilled technicians, and challenges in implementing automated detection. This research introduces a novel biosensor, utilizing aggregation-induced emission nanoparticles (AIENPs) and integrated with a digital microfluidic (DMF) workstation, designed for the sensitive, rapid, and automated detection of h-FABP in low-volume serum samples. AIENPs and magnetic beads in nanoscale were served as the capture particles and the fluorescent probe, which were linked covalently to anti-h-FABP antibodies respectively. The approach was based on a sandwich immunoassay and performed on a fully automated DMF workstation with assay time by 15 min. We demonstrated the determination of h-FABP in serum samples with detection limit of 0.14 ng/mL using this biosensor under optimal condition. Furthermore, excellent correlations (R2 = 0.9536, n = 50) were obtained between utilizing this biosensor and commercialized ELISA kits in clinical serum detecting. These results demonstrate that our flexible and reliable biosensor is suitable for direct integration into clinical diagnostics, and it is expected to be promising diagnostic tool for early detection and screening tests as well as prognosis evaluation for AMI patients.
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Técnicas Biosensibles , Proteína 3 de Unión a Ácidos Grasos , Infarto del Miocardio , Nanopartículas , Técnicas Biosensibles/instrumentación , Humanos , Proteína 3 de Unión a Ácidos Grasos/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/sangre , Nanopartículas/química , Límite de Detección , Biomarcadores/sangre , Proteínas de Unión a Ácidos Grasos/sangre , Proteínas de Unión a Ácidos Grasos/análisis , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Microfluídica/métodos , Diseño de Equipo , Anticuerpos Inmovilizados/química , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
The development of photoelectrochemical (PEC) biosensors plays a critical role in enabling timely intervention and personalized treatment for cardiac injury. Herein, a novel approach is presented for the fabrication of highly sensitive PEC biosensor employing Bi2O3/MgIn2S4 heterojunction for the ultrasensitive detection of heart fatty acid binding protein (H-FABP). The Bi2O3/MgIn2S4 heterojunction, synthesized through in-situ growth of MgIn2S4 on Bi2O3 nanoplates, offers superior attributes including a larger specific surface area and more homogeneous distribution, leading to enhanced sensing sensitivity. The well-matched valence and conduction bands of Bi2O3 and MgIn2S4 effectively suppress the recombination of photogenerated carriers and facilitate electron transfer, resulting in a significantly improved photocurrent signal response. And the presence of the secondary antibody marker (ZnSnO3) introduces steric hindrance that hinders electron transfer between ascorbic acid and the photoelectrode, leading to a reduction in photocurrent signal. Additionally, the competition between the ZnSnO3 marker and the Bi2O3/MgIn2S4 heterojunction material for the excitation light source further diminishes the photocurrent signal response. After rigorous repeatability and selectivity tests, the PEC biosensor exhibited excellent performance, and the linear detection range of the biosensor was determined to be 0.05 pg/mL to 100 ng/mL with a remarkable detection limit of 0.029 pg/mL (S/N = 3).
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Técnicas Biosensibles , Bismuto , Técnicas Electroquímicas , Técnicas Biosensibles/métodos , Bismuto/química , Técnicas Electroquímicas/métodos , Electrodos , Humanos , Procesos Fotoquímicos , Sulfuros/química , Límite de Detección , Proteínas de Unión a Ácidos Grasos/análisis , Indio/química , Compuestos de Zinc/química , Compuestos de Estaño/químicaRESUMEN
OBJECTIVE: Acute intestinal necrosis (AIN) is a disease with devastating high mortality. AIN due to obstructed arterial blood flow has a blurred clinical presentation. Timely diagnosis is paramount, and a blood-based biomarker is warranted to increase patient survival. We aimed to assess intestinal fatty acid binding protein (I-FABP) and endothelin-1 as diagnostic biomarkers for AIN. To our knowledge, this is the first study exploring endothelin-1 in AIN patients from a general surgical population. DESIGN: We conducted a single-centre nested case-control study comparing acutely admitted AIN patients to age- and sex-matched non-AIN patients during 2015-2016. I-FABP and endothelin-1 were analysed using an enzyme-linked immunosorbent assay. L-lactate levels were also measured in all patients. Cut-offs were estimated using receiver operator characteristic curves, and the diagnostic performance was estimated using the area under the receiver operator characteristic curve (AUC). RESULTS: We identified 43 AIN patients and included 225 matched control patients. Median levels of I-FABP, endothelin-1 and L-lactate were 3550 (IQR: 1746-9235) pg/ml, 3.91 (IQR: 3.33-5.19) pg/ml and 0.92 (IQR: 0.74-1.45) mM in AIN patients and 1731 (IQR: 1124-2848) pg/ml, 2.94 (IQR: 2.32-3.82) pg/ml and 0.85 (IQR: 0.64-1.21) mM in control patients, respectively. The diagnostic performances of endothelin-1 and of I-FABP + endothelin-1 combined were moderate. Endothelin-1 alone revealed an AUC of 0.74 (0.67; 0.82). The sensitivity and specificity of endothelin-1 were 0.81 and 0.64, respectively. CONCLUSION: I-FABP and endothelin-1 are promising biomarkers for AIN, with moderate diagnostic performance compared with the commonly used biomarker L-lactate. PREREGISTRATION: ClinicalTrials.gov: NCT05665946.
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Enfermedades Intestinales , Enfermedades Vasculares , Humanos , Estudios de Casos y Controles , Endotelina-1 , Proteínas de Unión a Ácidos Grasos/análisis , Biomarcadores , Necrosis , LactatosRESUMEN
INTRODUCTION: Delayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l-FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l-FABP and NGAL are specific markers for detection of liver and/or kidney injuries. PATIENTS AND METHODS: Traumatized patients with an age ≥18 years and an abdominal injury (AISabd≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury ("Abd") and 10 patients had an abdominal injury with hemorrhagic shock ("HS Abd"). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 ("noAbd") were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l-FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma. RESULTS: All patient groups had a median ISS≥25. In ER, median l-FABP levels were significantly higher in "HS Abd" group (1209.2 ng/ml [IQR=575.2-1780.3]) compared to "noAbd" group (36.4 ng/ml [IQR=14.8-88.5]), and to "Abd" group (41.4 ng/ml [IQR=18.0-235.5]), p<0.001. In matched-pair-analysis l-FABP levels in the group "Abd" were significantly higher (108.3 ng/ml [IQR=31.4-540.9]) compared to "noAbd" (26.4 ng/ml [IQR=15.5-88.8]), p = 0.0016. l-FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l-FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l-FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in "HS Abd" group (115.9 ng/ml [IQR=90.6-163.8]) compared to "noAbd" group (58.5 ng/ml [IQR=41.0-89.6],p<0.001) and "Abd" group (70.5 ng/ml [IQR=53.3-115.5], p<0.05). The group "Abd" showed significant higher median NGAL levels compared to "noAbd", p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock. CONCLUSION: L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l-FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same.
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Traumatismos Abdominales , Lesión Renal Aguda , Choque Hemorrágico , Humanos , Adolescente , Lipocalina 2/análisis , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/complicaciones , Lipocalinas , Proteínas de Fase Aguda/análisis , Biomarcadores , Traumatismos Abdominales/complicaciones , Traumatismos Abdominales/diagnóstico , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Proteínas de Unión a Ácidos Grasos/análisis , CreatininaRESUMEN
PURPOSE: Subjects with obesity may exhibit an increase in serum TSH concentrations. Several mechanisms have been proposed to explain this association, including the presence of a compensatory mechanism to counterbalance an accelerated turnover of thyroid hormones in subjects with obesity. This study aimed at evaluating whether the thyroids of subjects with obesity differs from those of normal-weight individuals regarding histology and gene expression profiling. METHODS: Ninety-eight patients were selected among those scheduled for thyroidectomy. At histology, thyroid tissue samples were investigated for the presence of adipocytes and/or lymphocyte infiltration. In a subset of patients, the expression at mRNA level of several genes involved in metabolic pathways and immune cell-related mechanisms was quantified by NanoString Technology. RESULTS: The presence of adipose cells was documented in thyroid specimens from 40% normal weight, 52.9% overweight and 73.5% patients with obesity. The number of infiltrating adipocytes was greater in specimens of patients with overweight or obesity compared to normal weight. The lymphocytes common antigen (CD45) and mast cell (MC) scores, and the number of CD3+ and CD8+ lymphocytes were higher in patients with overweight and obesity than in normal-weight subjects. Several genes involved in metabolic pathways were differently expressed in patients with overweight or obesity compared to normal weight, with upregulation of Leptin receptor and downregulation of Fatty Acid-Binding Protein 5. CONCLUSIONS: Increased BMI is associated with adipocyte and lymphocyte infiltration of the thyroid, not related to an autoimmune process, which might affect thyroid function in subjects with obesity. A differential gene expression profiling of metabolic and immune pathways in thyroid tissues of patients with obesity was also observed.
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Proteínas de Unión a Ácidos Grasos/análisis , Obesidad , Receptores de Leptina/análisis , Subgrupos de Linfocitos T , Glándula Tiroides , Hormonas Tiroideas/metabolismo , Adipocitos/inmunología , Adipocitos/patología , Índice de Masa Corporal , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Inmunidad Celular , Masculino , Redes y Vías Metabólicas , Persona de Mediana Edad , Obesidad/diagnóstico , Obesidad/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/patología , Glándula Tiroides/metabolismo , Glándula Tiroides/patologíaRESUMEN
BACKGROUND & AIMS: Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC. METHODS: A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison. RESULTS: Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis. CONCLUSIONS: Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC. LAY SUMMARY: Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis.
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Insuficiencia Hepática Crónica Agudizada/diagnóstico , Proteínas de Unión a Ácidos Grasos/análisis , Proteínas de Unión a Ácidos Grasos/orina , Insuficiencia Hepática Crónica Agudizada/sangre , Insuficiencia Hepática Crónica Agudizada/orina , Anciano , Biomarcadores/análisis , Biomarcadores/sangre , Biomarcadores/orina , Proteínas de Unión a Ácidos Grasos/sangre , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estadísticas no ParamétricasRESUMEN
OBJECTIVES: SARS-CoV-2 exhibits tropism for the gastrointestinal tract; however, lesions in enterocytes and their correlation with disease severity and patient prognosis are still unknown. METHODS: SARS-CoV-2 patients were enrolled in 5 medical centres in São Paulo, Brazil and their clinical characteristics and laboratory findings recorded. At admission, day 7 and day 14 of hospitalisation, plasma and urine samples were collected, and cytokine levels and intestinal fatty acid-binding protein (I-FABP) concentrations measured. RESULTS: COVID-19 patients displayed ≈48-, 74- and 125-fold increased urinary I-FABP levels at admission (n=283; P<0.001), day 7 (n=142; P<0.01) and day 14 (n=75; P<0.01) of hospitalisation. Critically ill patients and nonsurvivors showed higher I-FABP concentrations compared with patients with less severe illness. At admission, infected patients demonstrated enhanced production of plasma interferon (IFN)-γ and interleukin (IL)-6. The receiver operating characteristic curve suggested I-FABP as a biomarker for COVID-19 disease severity at admission (P<0.0001; Youden index=6.89; area under the curve=0.699). Patients with I-FABP ≥6.89 showed higher IL-6 and C-reactive protein levels (P<0.001) at admission and had a prolonged length of hospital stay. CONCLUSIONS: Our findings revealed damage to enterocytes in SARS-CoV-2 infection, which is associated with illness severity, poor prognosis and exacerbated inflammatory response.
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COVID-19 , Proteínas de Unión a Ácidos Grasos/análisis , Biomarcadores , Brasil , Proteína C-Reactiva , COVID-19/diagnóstico , Enterocitos/virología , Humanos , Interferón gamma , Interleucina-6 , Estudios ProspectivosRESUMEN
ABSTRACT: Osteoarthritis (OA) seriously affects human health and brings a heavy social burden. This study aimed to identify new biomarkers involved in OA. Differential expression analysis and gene set enrichment analysis were performed on the microarray data set of OA. Identify key genes from immune-related DEGs and verify their expression in the validation set. CIBERSORT was used to analyze the infiltration of immune cells. The correlation between key genes and immune cells were conducted. A total of 1779 DEGs were identified in GSE82107. Gene set enrichment analysis results of top 4 for hallmark revealed the enrichment of DEGs were associated with genes in "HALLMARK_TNFA_SIGNALING_VIA_NFKB", "HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION", "HALLMARK_INFLAMMATORY_RESPONSE" and "HALLMARK_HYPOXIA". A total of 108 immune-related DEGs were identified from the overlap between 2498 immune-related genes and 1779 DEGs. The expression of top 6 immune-related DEGs including ADIPOQ, FABP4, FOS, IGLC1, IGLV1-44 and leptin were measured in the validation set, the results shown that IGLC1 and IGLV1-44 might play a key role in the synovial membrane of OA. A total of 8 kinds of cells including B cells memory, Plasma cells, T cells CD4 memory resting, T cells gamma delta, natural killer cells activated, macrophages M0, Mast cells resting and Mast cells activated have significant differences in infiltration between the OA group and the control group. Besides, the expressions of IGLC1 and IGLV1-44 are highly correlated. Our results indicated that IGLC1 and IGLV1-44 may play the role of immune-related biomarkers in OA.
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Biomarcadores/análisis , Osteoartritis/fisiopatología , Adiponectina/análisis , Biología Computacional/instrumentación , Biología Computacional/métodos , Bases de Datos Genéticas/estadística & datos numéricos , Proteínas de Unión a Ácidos Grasos/análisis , Humanos , Osteoartritis/genética , Proteínas Proto-Oncogénicas c-fos/análisisRESUMEN
Lung cancer, the leading cause of cancer mortality worldwide has a poor prognosis. To develop a non-invasive method for early lung cancer detection, exhaled breath condensate (EBC) was explored in this study. EBC samples were collected from lung cancer patients (n= 10) and healthy controls (n= 10), and a proteomic study was performed to identify potential biomarkers. Data-dependent acquisition was used to build the spectral library, and a data-independent acquisition (DIA) approach was applied for quantification of EBC proteomics. A total of 1151 proteins were identified, and several proteins were significantly upregulated in the lung cancer group compared to the control group. The Gene Ontology analysis revealed that most of the proteins were located within several organelles in the cells and were involved in binding and catalytic activity, and the Kyoto Encyclopedia Genes and Genomes results revealed that the proteins were mainly related to organismal systems and human disease. And S100A11, ANXA1, ENO1, and FABP5 might play a vital role in the EBC proteome. In summary, we demonstrated that the DIA-based quantification method was efficient in performing proteomic analysis in individual EBC samples, and some of the proteins might be novel biomarkers for lung cancer.
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Neoplasias Pulmonares , Proteómica , Anexina A1/análisis , Biomarcadores/análisis , Biomarcadores de Tumor/análisis , Pruebas Respiratorias/métodos , Proteínas de Unión al ADN/análisis , Espiración , Proteínas de Unión a Ácidos Grasos/análisis , Humanos , Neoplasias Pulmonares/diagnóstico , Fosfopiruvato Hidratasa/análisis , Proyectos Piloto , Proteoma/metabolismo , Proteómica/métodos , Proteínas S100/análisis , Proteínas Supresoras de Tumor/análisisRESUMEN
The intestinal barrier plays a crucial role in the absorption of nutrients and in preventing the entry of pathogenic microorganisms and toxic molecules. Several studies have shown a compromised intestinal barrier associated with low-grade inflammation in the small intestinal mucosa in celiac disease, inflammatory bowel disease, and irritable bowel syndrome (IBS), particularly in IBS with diarrhea (IBS-D). In light of these new data, IBS is no longer considered a functional disease but rather a heterogeneous syndrome that has yet to be carefully studied. Therefore, investigating the integrity and function of the intestinal barrier is now essential to improving knowledge of the pathophysiology of IBS-D and to improving the management of IBS-D patients. However, the study of the intestinal barrier must clarify some still unsolved methodological aspects and propose standardised assays before becoming a useful diagnostic tool. In this framework, this review will discuss data about the tests that noninvasively evaluate the integrity and functionality of the human intestinal barrier, paying particular attention to patients with IBS-D, in both clinical and research situations.
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Biomarcadores/análisis , Diarrea/fisiopatología , Síndrome del Colon Irritable/fisiopatología , Amina Oxidasa (conteniendo Cobre)/análisis , Diarrea/diagnóstico , Disbiosis/diagnóstico , Disbiosis/etiología , Proteínas de Unión a Ácidos Grasos/análisis , Microbioma Gastrointestinal , Humanos , Absorción Intestinal , Síndrome del Colon Irritable/diagnósticoRESUMEN
BACKGROUND: Some studies have investigated the diagnostic value of intestinal fatty acid binding protein (I-FABP) for acute intestinal ischemia (II), but the results were not always consistent. Therefore, we performed a systematic review and meta-analysis to determine the diagnostic accuracy of I-FABP for II. METHODS: Publications included in the PubMed and EMBASE before April 7, 2019 were retrieved to identify studies investigating the diagnostic accuracy of I-FABP for II. The Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the quality of eligible studies. Diagnostic accuracy of I-FABP in all eligible studies was pooled by a bivariate model. Summary receiver operating characteristic (ROC) curves (AUC) were constructed to calculate the overall diagnostic accuracy of I-FABP. RESULTS: A total of 10 studies with 1,265 (219 IIs and 1,046 controls) subjects were included in this systematic review and meta-analysis. The major design weaknesses of included studies were patient selection bias. The overall diagnostic sensitivity, specificity, and AUC of I-FABP were 0.75 (95% CI: 0.68 - 0.82), 0.85 (95% CI: 0.74 - 0.92), and 0.82 (95% CI: 0.79 - 0.86), respectively. In patients with acute abdominal pain, the sensitivity, specificity, and AUC of I-FABP were 0.71 (95% CI: 0.59 - 0.81), 0.89 (95% CI: 0.69 - 0.97) and 0.80 (95% CI: 0.76 - 0.83), respectively. CONCLUSIONS: I-FABP has moderate diagnostic accuracy for II. Due the patient selection bias of available studies, further studies with rigorous design are needed to evaluate the diagnostic accuracy of I-FABP for II.
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Proteínas de Unión a Ácidos Grasos/análisis , Pruebas Hematológicas , Enfermedades Intestinales , Mucosa Intestinal , Isquemia , Diagnóstico Precoz , Pruebas Hematológicas/métodos , Pruebas Hematológicas/normas , Humanos , Enfermedades Intestinales/sangre , Enfermedades Intestinales/diagnóstico , Mucosa Intestinal/irrigación sanguínea , Mucosa Intestinal/metabolismo , Isquemia/sangre , Isquemia/diagnóstico , Reproducibilidad de los ResultadosRESUMEN
Recently emerged liposomal photoelectrochemical (PEC) bioanalysis has brought new opportunities for biosensor development. This work presents the new concept of liposome-assisted enzymatic modulation of plasmonic photoelectrochemistry for PEC bioanalysis, which was exemplified by an Au nanoclusters (NCs)-sensitized nanoporous TiO2 nanotubes (Au NC@TiO2 NT) photoelectrode and an alkaline phosphatase (ALP)-loaded liposomal immunoassay of heart-type fatty acid binding protein in a 96-well plate. After sandwich immunorecognition and subsequent lysis treatment, enzymatically generated ascorbic acid by the released ALP was directed to reduce Au3+ into Au nanoparticles using the Au NCs as seeds, leading to the in situ change of the photoelectrochemistry of the electrode and corresponding reduction of the photocurrent. The depressed signal could be correlated with the target concentration with good analytical performance in terms of sensitivity and selectivity. This work features the liposome-assisted enzymatic modulation of plasmonic photoelectrochemistry, which provides a new protocol for general PEC bioanalysis development.
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Fosfatasa Alcalina/química , Proteínas de Unión a Ácidos Grasos/análisis , Oro/química , Inmunoensayo , Titanio/química , Fosfatasa Alcalina/metabolismo , Técnicas Biosensibles , Técnicas Electroquímicas , Electrodos , Humanos , Liposomas/química , Tamaño de la Partícula , Procesos Fotoquímicos , Propiedades de SuperficieRESUMEN
BACKGROUND: Necrotizing enterocolitis (NEC) is a neonatal disease with its pathogenesis still not well understood, although it is hypothesized to be related to decreased perfusion of the intestinal wall. The current study aimed to evaluate the plasma lactate levels and assess the validity of plasma and urinary intestinal fatty acid binding protein (I-FABPp and I-FABPu/Cru respectively) in NEC. METHODS: The study included 55 neonates with variable Bell's stages who were comparable with 23 matched controls. Colorimetric assays of plasma lactate and ELISA assays of I-FABP in both serum and urine of the included neonates have been performed. RESULTS: There were significantly higher median levels of I-FABPp, I-FABPu and lactate among cases (2.84 ng/ml, 1.74 ng/g creat. and 32.34 mg/dl, respectively) compared with controls (0.16 ng/ml, 0.60 ng/g creat. and 15.33 mg/dl, respectively) with p Ë 0.05 for all. I-FABPp at cut-off point >3.24 ng/ml showed 90% sensitivity, 72% specificity, PPV = 52.6%, NPP = 94.7%, while for I-FABPu (at cut-off point > 2.93 ng/g creat.) those values were 90%, 92%, 81.8% and 95.8% respectively, in discriminating stage IIIA from stage II with p = 0.001. In predicting surgical NEC, I-FABPp at the cut-off point of 6.95 ng/ml revealed 75% sensitivity, 100% specificity, PPV = 100%, NPP = 95%, while for I-FABPu (cut-off point>4.13 ng/g creat.) they were 100%, 76.19%, 44.4 %and 100%, p = 0.04. CONCLUSION: s: In addition to clinical judgment, sonographic data and plasma lactate, I-FABPp was shown to be a specific marker for early identification of surgical NEC, while I-FABPu could be more useful for differentiating Bell's stage II from stage III.
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Enterocolitis Necrotizante/diagnóstico , Proteínas de Unión a Ácidos Grasos/análisis , Ácido Láctico/sangre , Biomarcadores/análisis , Enterocolitis Necrotizante/metabolismo , Enterocolitis Necrotizante/cirugía , Proteínas de Unión a Ácidos Grasos/sangre , Proteínas de Unión a Ácidos Grasos/orina , Femenino , Humanos , Recién Nacido , Masculino , UltrasonografíaRESUMEN
Microfluidic technologies offer new platforms for biosensing in various clinical and point-of-care (POC) applications. Currently, at the clinical settings, the gold standard diagnostic platforms for multiplexed sensing are multi-step, time consuming, requiring expensive and bulky instruments with a constant need of electricity which makes them unsuitable for resource-limited or POC settings. These technologies are often limited by logistics, costly assays and regular maintenance. Although there have been several attempts to miniaturize these diagnostic platforms, they stand short of batch fabrication and they are dependent on complementary components such as syringe pumps. Here, we demonstrated the development and clinical testing of a disposable, multiplexed sensing device (ToMMx), which is a portable, high-throughput and user-friendly microfluidic platform. It was built with inexpensive plastic materials and operated manually without requiring electrical power and extensive training. We validated this platform in a small cohort of 50 clinical samples from patients with cardiovascular diseases and healthy controls. The platform is rapid and gives quantifiable results with high sensitivity, as low as 5.29 pg/mL, from only a small sample volume (4 µL). ToMMx platform was compared side-by-side with commercial ELISA kits where the total assay time is reduced 15-fold, from 5 h to 20 min. This technology platform is broadly applicable to various diseases with well-known biomarkers in diagnostics and monitoring, especially with potential future impact at the POC settings.
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Técnicas Biosensibles/instrumentación , Dispositivos Laboratorio en un Chip , Sistemas de Atención de Punto , Biomarcadores/análisis , Enfermedades Cardiovasculares/diagnóstico , Diseño de Equipo , Proteínas de Unión a Ácidos Grasos/análisis , Humanos , Técnicas Analíticas Microfluídicas/instrumentación , Péptido Natriurético Encefálico/análisis , Fragmentos de Péptidos/análisis , Troponina I/análisisRESUMEN
Background: Hemorrhagic shock can lead to intestinal damage with subsequent hyperinflammation and multiple organ dysfunction syndrome (MODS). The intestinal fatty acid-binding protein (I-FABP) is solely expressed in the intestine and is released extracellulary after tissue damage. This study evaluates the validity of I-FABP as an early biomarker to detect hemorrhagic shock and abdominal injury. Patients and methods: Severely injured patients with an Injury Severity Score (ISS) ≥ 16 points and an age ≥ 18 years, admitted from January 2010 to December 2016, were included. Overall, 26 patients retrospectively presented with hemorrhagic shock to the emergency room (ER): 8 patients without abdominal injury ("HS noAbd") and 18 patients with abdominal injury ("HS Abd"). Furthermore, 16 severely injured patients without hemorrhagic shock and without abdominal injury ("noHS noAbd") were retrospectively selected as controls. Plasma I-FABP levels were measured at admission to the ER and up to 3 days posttraumatic (d1-d3). Results: Median I-FABP levels were significantly higher in the "HS Abd" group compared with the "HS noAbd" group (28,637.0 pg/ml [IQR = 6372.4-55,550.0] vs. 7292.3 pg/ml [IQR = 1282.5-11,159.5], p < 0.05). Furthermore, I-FABP levels of both hemorrhagic shock groups were significantly higher compared with the "noHS noAbd" group (844.4 pg/ml [IQR = 530.0-1432.9], p < 0.05). The time course of I-FABP levels showed a peak on the day of admission with a subsequent decline in the post-traumatic course. Furthermore, significant correlations between I-FABP levels and clinical parameters of hemorrhagic shock, such as hemoglobin, lactate value, systolic blood pressure (SBP), and shock index, were found.The optimal cut-off level of I-FABP for detection of hemorrhagic shock was 1761.9 pg/ml with a sensitivity of 85% and a specificity of 81%. Conclusion: This study confirmed our previous observation that I-FABP might be used as a suitable early biomarker for the detection of abdominal injuries in general. In addition, I-FABP may also be a useful and a promising parameter in the diagnosis of hemorrhagic shock, because of reflecting low intestinal perfusion.
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Traumatismos Abdominales/sangre , Biomarcadores/análisis , Proteínas de Unión a Ácidos Grasos/análisis , Choque Hemorrágico/sangre , Traumatismos Abdominales/diagnóstico , Traumatismos Abdominales/fisiopatología , Adulto , Biomarcadores/sangre , Proteínas de Unión a Ácidos Grasos/sangre , Femenino , Alemania , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica , Proyectos Piloto , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/fisiopatología , Heridas y Lesiones/sangre , Heridas y Lesiones/complicacionesRESUMEN
OBJECTIVE: To explore the relationship between FABP4 and FABP6 expression and the pathogenesis of colorectal cancer (CRC) and their potential as biomarkers in the diagnosis of CRC. METHODS: In total, 100 CRC patients and 100 controls were enrolled. The serum levels of FABP4 and FABP6 were detected by enzyme-linked immunosorbent assay (ELISA) before and 2 weeks after radical resection of CRC. The protein expressions of FABP4 and FABP6 were observed in colorectal tumor tissues and adjacent tissues by immunohistochemistry and western blot, respectively. The diagnostic performance of FABP4 and FABP6 in patients with CRC was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The serum levels of FABP4 and FABP6 in patients with CRC were higher than the levels in the controls before surgery (P < 0.001), and significantly decreased at 2 weeks after operation (P < 0.001). Immunohistochemistry showed that FABP4 and FABP6 were mainly distributed in the cytoplasm of human colorectal tumor tissues, and only a small amount distributed in adjacent tissues. Western blot revealed that the protein expressions of FABP4 and FABP6 were significantly higher in tumor tissues than in adjacent tissues (P < 0.001, P = 0.002, respectively). Tumors with high and low FABP4 and FABP6 expression have no significant correlation in tumor size, tumor site, distant organ and lymph node metastasis, histologic grade, lymphatic permeation, neurological invasion, vascular invasion, and Duke's and TNM classification. Multivariate logistic regression analysis showed that FABP4 and FABP6 were independent risk factors for CRC (adjusted odds ratio 1.916; 95%CI 1.340-2.492; P < 0.001; adjusted odds ratio 2.162; 95%CI 1.046, 1.078); P < 0.001, respectively). In discriminating CRC from the normal control, the optimal sensitivity of FABP4 and FABP6 were 93.20% (95%CI 87.8-96.7) and 83.70% (95%CI 76.7-89.3), respectively, while the optimal specificity of FABP4 and FABP6 were 48.8% (95%CI 39.8-57.9) and 58.4% (95%CI 49.2-67.1), respectively. When combined detection of serum carcinoembryonic (CEA) and FABP4 and FABP6, the optimal sensitivity and specificity were 61.33% (95%CI 53.0-69.2) and 79.82% (95%CI 71.3-86.8), respectively. CONCLUSION: Increased expression of FABP4 and FABP6 not only were strong risk factors for the development of CRC but could also represent a potential biomarker for CRC diagnosis in Chinese patients. Combined detection of CEA with FABP4 and FABP6 could improve the diagnostic efficacy of CRC.
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Neoplasias Colorrectales/etiología , Proteínas de Unión a Ácidos Grasos/análisis , Hormonas Gastrointestinales/análisis , Adulto , Anciano , Antígeno Carcinoembrionario/análisis , Neoplasias Colorrectales/química , Neoplasias Colorrectales/patología , Femenino , Humanos , Inmunohistoquímica , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE OF REVIEW: Fatty acid-binding proteins (FABPs) are a family of small, abundant proteins with highly tissue-specific expression patterns whose different functions remain incompletely understood. The purpose of this review is to summarize recent findings regarding FABP functions and mechanisms of action, including their potential utilization as serum markers of tissue-specific metabolic diseases. RECENT FINDINGS: FABPs are important not only in their tissues of origin but also appear to influence the metabolism and function of tissues distal to their sites of expression. This may be secondary to metabolic changes in their primary tissues, and/or a result of FABP secretion from these tissues leading to effects on distal sites. Their levels in the circulation are increasingly explored as potential biomarkers for tissue-specific disease prognosis and progression. SUMMARY: The nine fatty acid-binding members of the FABP family have unique tissue-specific functions and important secondary effects on tissues in which they are not expressed. For many of the FABPs, circulating levels may be indicative of disease processes related to their primary tissues, and may influence physiological function in distal tissues.
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Proteínas de Unión a Ácidos Grasos , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Proteínas de Unión a Ácidos Grasos/análisis , Proteínas de Unión a Ácidos Grasos/metabolismo , Proteínas de Unión a Ácidos Grasos/fisiología , Ácidos Grasos/metabolismo , Humanos , Ratones , Neoplasias/diagnóstico , Neoplasias/metabolismo , Obesidad/diagnóstico , Obesidad/metabolismo , Especificidad de ÓrganosRESUMEN
Acute mesenteric ischemia (AMI) is one of the most severe diagnostic and therapeutic vital emergencies. This affection is characterized by the insufficient blood supply to the gastrointestinal tract, related to an occlusive or non-occlusive mechanism, resulting in an ischemic and inflammatory injury that may progress to necrosis of the intestinal wall. The clinical picture is nonspecific, dominated by acute abdominal pain. At present, no early biological marker is commonly used in clinical practice for diagnostic purposes. The purpose of this review was to review the markers that have been evaluated in this condition. Among the biological blood markers which have shown a diagnostic interest in the IMA, there are notably the two stereoisomers of lactate (D and L), D-dimers, and alpha glutathione transferase. More specific markers include the intestinal fatty acid binding protein or I-FABP, which is a marker of enterocyte necrosis, citrulline, a marker of enterocyte mass, or Smooth muscle protein 22 (SM22) marker for muscle damage. The early diagnosis of intestinal ischemia remains a challenge. It is likely that in the future IMA's biomarker research will be better customized and adapted to the physiopathological mechanism. More global approaches (proteomics, metabolomics) should also make it possible to identify new biomarkers.
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Biomarcadores/sangre , Técnicas de Laboratorio Clínico/métodos , Isquemia Mesentérica/diagnóstico , Enfermedad Aguda , Biomarcadores/análisis , Citrulina/análisis , Citrulina/sangre , Técnicas de Laboratorio Clínico/tendencias , Diagnóstico Precoz , Proteínas de Unión a Ácidos Grasos/análisis , Proteínas de Unión a Ácidos Grasos/sangre , Glutatión Transferasa/análisis , Glutatión Transferasa/sangre , Humanos , Mediadores de Inflamación/análisis , Mediadores de Inflamación/sangre , Isoenzimas/análisis , Isoenzimas/sangre , Isquemia Mesentérica/sangre , Proteínas de Microfilamentos/análisis , Proteínas de Microfilamentos/sangre , Proteínas Musculares/análisis , Proteínas Musculares/sangre , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIM: Fatty acid-binding protein-4 (FABP4) is an adipokine associated with obesity and signs of the metabolic syndrome. We aimed to investigate at birth in term neonates with normal and abnormal intrauterine growth concentrations of FABP4 and associate them with various perinatal parameters. METHODS: Serum cord blood FABP4 levels were prospectively determined by ELISA in 80 singleton term appropriate-for-gestational-age (AGA), intrauterine growth-restricted (IUGR) and large-for-gestational-age (LGA) neonates. RESULTS: Compared to the AGA group, cord blood FABP4 levels were increased in the IUGR and LGA groups. Additionally, they were higher in early-term than full-term neonates. A significant U-shaped correlation was recorded between serum FABP4 levels and birthweight. A significant negative correlation between cord blood FABP4 and gestational age in the whole study population was noted. CONCLUSION: Cord blood FABP4 levels were significantly higher at the extremes of foetal growth at term and negatively correlated with gestational age, being increased in early-term versus full-term neonates. Further longitudinal studies with larger sample sizes are required to elucidate FABP4 implication in foetal growth and its association with future adverse cardiometabolic outcomes in the offspring.
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Peso al Nacer , Proteínas de Unión a Ácidos Grasos/análisis , Sangre Fetal/química , Femenino , Desarrollo Fetal , Edad Gestacional , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Regulación hacia ArribaRESUMEN
Hepatorenal syndrome (HRS) is a form of kidney function impairment that characteristically occurs in cirrhosis. Recent changes in terminology have led to acute HRS being referred to as acute kidney injury (AKI)-HRS and chronic HRS as chronic kidney disease (CKD)-HRS. AKI-HRS is characterized by a severe impairment of kidney function owing to vasoconstriction of the renal arteries in the absence of substantial abnormalities in kidney histology. Pathogenetic mechanisms involve disturbances in circulatory function due to a marked splanchnic arterial vasodilation, which triggers the activation of vasoconstrictor factors. An intense systemic inflammatory reaction that is characteristic of advanced cirrhosis may also be involved. The main triggering factors of AKI-HRS are bacterial infections, particularly spontaneous bacterial peritonitis. The diagnosis of AKI-HRS is a challenge because of a lack of specific diagnostic tools and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The prognosis of patients with AKI-HRS is poor, with a median survival of ≤3 months. The ideal treatment for AKI-HRS is liver transplantation in patients without contraindications. Medical therapy consists of vasoconstrictor drugs to counteract splanchnic arterial vasodilation together with volume expansion with albumin. Effective measures to prevent AKI-HRS include early identification and treatment of bacterial infections and the administration of albumin in patients with spontaneous bacterial peritonitis.