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The challenge of treating corneal scarring through keratoplasties lies in the limited availability of donor tissue. Various studies have shown the therapeutic use of cultivated corneal stromal stem cells (CSSCs) to mitigate tissue inflammation and suppress fibrosis and scar tissue formation in preclinical corneal wound models. To develop CSSC therapy for clinical trials on patients with corneal scarring, it is necessary to generate clinical-grade CSSCs in compliant to Good Manufacturing Practice (GMP) regulations. This chapter elucidates human CSSC isolation, culture, and cryopreservation under GMP-compliant conditions. It underscores quality assessment encompassing morphological traits, expression of stemness markers, anti-inflammatory activity, and keratocyte differentiation potency.
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Técnicas de Cultivo de Célula , Diferenciación Celular , Sustancia Propia , Humanos , Técnicas de Cultivo de Célula/métodos , Sustancia Propia/citología , Separación Celular/métodos , Criopreservación/métodos , Células Madre/citología , Células Madre/metabolismo , Células Cultivadas , Biomarcadores , Células del Estroma/citologíaRESUMEN
Metabolomics is the study of low molecular weight biochemical molecules (typically <1500 Da) in a defined biological organism or system. In case of food systems, the term "food metabolomics" is often used. Food metabolomics has been widely explored and applied in various fields including food analysis, food intake, food traceability, and food safety. Food safety applications focusing on the identification of pathogen-specific biomarkers have been promising. This chapter describes a nontargeted metabolite profiling workflow using gas chromatography coupled with mass spectrometry (GC-MS) for characterizing three globally important foodborne pathogens, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica, from selective enrichment liquid culture media. The workflow involves a detailed description of food spiking experiments followed by procedures for the extraction of polar metabolites from media, the analysis of the extracts using GC-MS, and finally chemometric data analysis using univariate and multivariate statistical tools to identify potential pathogen-specific biomarkers.
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Biomarcadores , Microbiología de Alimentos , Cromatografía de Gases y Espectrometría de Masas , Listeria monocytogenes , Metabolómica , Metabolómica/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Biomarcadores/análisis , Microbiología de Alimentos/métodos , Listeria monocytogenes/metabolismo , Listeria monocytogenes/aislamiento & purificación , Salmonella enterica/metabolismo , Escherichia coli O157/metabolismo , Escherichia coli O157/aislamiento & purificación , Enfermedades Transmitidas por los Alimentos/microbiología , MetabolomaRESUMEN
BACKGROUND: Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions. METHODS: In this meta-analysis, we searched for urinary C-C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions. RESULTS: We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75-0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71-0.79),0.71 (95 % CI 0.67-0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83-0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup analysis and meta-regression of CCL14-related studies revealed that CCL14 is the most appropriate biomarker for predicting persistent stage 2-3 AKI, with heterogeneity stemming from sample size and AKI staging. CONCLUSION: This meta-analysis discovered CCL14 as the best biomarker to predict persistent AKI, specifically persistent stage 2-3 AKI.
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Lesión Renal Aguda , Biomarcadores , Humanos , Biomarcadores/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/sangre , Lesión Renal Aguda/orina , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangreRESUMEN
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.
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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/sangreRESUMEN
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.
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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 CohortesRESUMEN
BACKGROUND-AIM: Methylmalonic acid (MMA) is currently the best biomarker of functional vitamin B12 deficiency. However, for a correct interpretation of the patient's results it is necessary to know its biological variation (BV). No BV data are available for urine MMA values, as measured by mass spectrometry. Hence, the aim of this study was to estimate the within- and between-person coefficients of variation (CVw, CVg) for MMA in a healthy population, and the associated index of individuality (II), as well as to define quality specifications based on BV and the reference change value (RCV). METHODS: Random urine samples from 34 healthy volunteers were collected over four consecutive weeks. Samples were stored at -80 °C until analysis in a single analytical run. MMA excretion was quantified by tandem liquid chromatography coupled to mass spectrometry (HPLC-MS/MS). Results were normalized to urine creatinine. The coefficients of variation were estimated by CV-ANOVA. Confidence intervals (95 %) were calculated. Quality specifications were defined according to international recommendations. RESULTS: A total of 128 samples were included. The coefficients of variation were CVw = 35.7 % (26.1-45.3) and CVg = 67.7 % (58.3-77.0). The associated II was 0.5 and the RCV was 88.1 %. CONCLUSION: Considering the II obtained, MMA in urine has high individuality, therefore, RCV is better to evaluate serial clinical results. Our results will contribute to a better clinical interpretation of this biomarker and will represent a great aid when defining analytical performance specifications for this magnitude.
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Ácido Metilmalónico , Humanos , Ácido Metilmalónico/orina , Masculino , Adulto , Femenino , España , Espectrometría de Masas en Tándem , Persona de Mediana Edad , Adulto Joven , Voluntarios Sanos , Cromatografía Líquida de Alta Presión , Biomarcadores/orinaRESUMEN
Long-term and excessive use of tetracycline hydrochloride (TC) can lead to its accumulation in the environment, which can cause water contamination, bacterial resistance, and food safety problems. 2,6-Pyridine dicarboxylic acid (DPA) is a major biomarker of Bacillus anthracis spores, and its rapid and sensitive detection is of great significance for disease prevention and counter-terrorism. A bifunctional ratiometric fluorescent nanoprobe has been fabricated to detect DPA and TC. 3,5-dicarboxyphenylboronic acid (BOP) was intercalated into layered europium hydroxide (LEuH) by the ion-exchange method and exfoliated into nanosheets as a fluorescent nanoprobe (PNP). DPA and TC could significantly enhance the red fluorescence of Eu3+ through the antenna effect under different excitation wavelengths, while the fluorescence of BOP can be used as a reference based on the constant emission intensity, realizing ratiometric detection. A low limit of detection (LOD) for the target (DPA: 9.7 nM, TC: 21.9 nM) can be achieved. In addition, visual detection of DPA and TC was realized using color recognition software based on the obvious color changes. This is the first ratiometric fluorescent nanoprobe based on layered rare-earth hydroxide (LRH) for the detection of DPA and TC simultaneously, which opens new ideas in the design of multifunctional probes.
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Bacillus anthracis , Biomarcadores , Colorantes Fluorescentes , Espectrometría de Fluorescencia , Esporas Bacterianas , Tetraciclina , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Bacillus anthracis/aislamiento & purificación , Biomarcadores/análisis , Tetraciclina/análisis , Límite de Detección , Ácidos Picolínicos/análisis , Carbunco/diagnósticoRESUMEN
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.
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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/sangreRESUMEN
BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.
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Angiotensina I , Fragmentos de Péptidos , Fibrosis Pulmonar , Humanos , Angiotensina I/sangre , Masculino , Femenino , Fibrosis Pulmonar/sangre , Fibrosis Pulmonar/diagnóstico , Fragmentos de Péptidos/sangre , Persona de Mediana Edad , Anciano , Estudios Longitudinales , Biomarcadores/sangre , COVID-19/sangre , COVID-19/complicaciones , COVID-19/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/sangreRESUMEN
Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.
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Arsénico , Exposición a Riesgos Ambientales , Estrés Oxidativo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , 8-Hidroxi-2'-Desoxicoguanosina , Arsénico/toxicidad , Biomarcadores/orina , China , Estudios Transversales , Daño del ADN , Pueblos del Este de Asia , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Estudios Longitudinales , Estrés Oxidativo/efectos de los fármacosRESUMEN
The prevalence of chronic kidney disease (CKD) continues to rise globally, paralleled by an increase in associated morbidity and mortality, as well as significant implications for patient quality of life and national economies. Chronic kidney disease often progresses unrecognized by patients and physicians, despite diagnosis relying on two simple laboratory measures: estimated glomerular filtration rate (eGFR) and urine analysis. GFR measurement has been grounded in renal physiology, specifically the concept of clearance, with creatinine identified as a suitable endogenous marker for estimating creatinine clearance (CrCl). On this foundation, various equations have been developed to calculate CrCl or estimated GFR (eGFR) using four variables that incorporate creatinine and certain demographic information, such as sex and age. However, creatinine measurement requires standardization to minimize assay variability across laboratories. Moreover, the accuracy of these equations remains contentious in certain patient subgroups. For these reasons, additional mathematical models have been devised to enhance CrCl estimation, for example, when urine collection is impractical, in elderly or debilitated patients, and in individuals with trauma, diabetes, or obesity. Presently, eGFR in adults can be immediately measured and reported using creatinine-based equations traceable through isotope dilution mass spectrometry. In conclusion, leveraging insights from renal physiology, eGFR can be employed clinically for early diagnosis and treatment of CKD, as well as a public health tool to estimate its prevalence.
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Creatinina , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica , Humanos , Creatinina/orina , Creatinina/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Reproducibilidad de los Resultados , Biomarcadores/orina , AdultoRESUMEN
BACKGROUND: Diabetic retinopathy (DR), a chronic and progressive microvascular complication of diabetes mellitus, substantially threatens vision and is a leading cause of blindness among working-age individuals worldwide. Traditional diagnostic methods, such as ophthalmoscopy and fluorescein angiography are nonquantitative, invasive, and time consuming. Analysis of protein biomarkers in tear fluid offers noninvasive insights into ocular and systemic health, aiding in early DR detection. This study introduces a surface acoustic wave (SAW) microchip that rapidly enhances fluorescence in bead-based immunoassays for the sensitive and noninvasive DR detection from human tear samples. RESULTS: The device facilitated particle mixing for immunoassay formation and particle concentration in the droplet, resulting in an enhanced immunofluorescence signal. This detachable SAW microchip allows the disposal of the cover glass after every use, thereby improving the reusability of the interdigital transducer and minimizing potential cross-contamination. A preliminary clinical test was conducted on a cohort of 10 volunteers, including DR patients and healthy individuals. The results demonstrated strong agreement with ELISA studies, validating the high accuracy rate of the SAW microchip. SIGNIFICANCE: This comprehensive study offers significant insights into the potential application of a novel SAW microchip for the early detection of DR in individuals with diabetes. By utilizing protein biomarkers found in tear fluid, the device facilitates noninvasive, rapid, and sensitive detection, potentially revolutionizing DR diagnostics and improving patient outcomes through timely intervention and management of this vision-threatening condition.
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Retinopatía Diabética , Lágrimas , Humanos , Lágrimas/química , Retinopatía Diabética/diagnóstico , Inmunoensayo/métodos , Sonido , Técnicas Biosensibles/instrumentación , Biomarcadores/análisis , Propiedades de SuperficieRESUMEN
Background: Systemic immune-inflammation index (SII) is a novel comprehensive inflammatory marker. Inflammation is associated with impaired lung function. We aimed to explore the possible relationship between SII and lung function to examine the potential of SII in predicting lung function decline. Methods: A cross-sectional survey was conducted using the data of the NHANES from 2007 to 2012. Multiple linear regression models were used to analyze the linear relationship between SII and pulmonary functions. Sensitivity analyses, subgroup analyses, and interaction tests were used to examine the robustness of this relationship across populations. Fitted smooth curves and threshold effect analysis were used to describe the nonlinear relationships. Results: A total of 10,125 patients were included in this study. After adjusting for all covariates, multiple linear regression model analysis showed that high Log2-SII level was significantly associated with decreased FVC(ß, -23.4061; 95% CI, -42.2805- -4.5317), FEV1(ß, -46.7730; 95% CI, -63.3371- -30.2089), FEV1%(ß, -0.7923; 95% CI, -1.1635- -0.4211), FEV1/FVC(ß, -0.6366; 95% CI, -0.8328- -0.4404) and PEF(ß, -121.4468; 95% CI,-164.1939- -78.6998). The negative correlation between Log2-SII and pulmonary function indexes remained stable in trend test and stratified analysis. Inverted U-shaped relationships between Log2-SII and FVC, FEV1, FEV1%, and PEF were observed, while a negative linear correlation existed between FEV1/FVC and Log2-SII. The cutoff values of the nonlinear relationship between Log2-SII and FVC, FEV1, FEV1%, PEF were 8.3736, 8.0688, 8.3745, and 8.5255, respectively. When SII exceeded the critical value, the lung function decreased significantly. Conclusion: This study found a close correlation between SII and pulmonary function indicators. This study investigated the SII threshold when lung functions began to decline in the overall population. SII may become a promising serological indicator for predicting lung function decline. However, prospective studies were needed further to establish the causal relationship between these two factors.
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Mediadores de Inflamación , Inflamación , Pulmón , Encuestas Nutricionales , Valor Predictivo de las Pruebas , Humanos , Masculino , Estudios Transversales , Femenino , Persona de Mediana Edad , Pulmón/fisiopatología , Pulmón/inmunología , Volumen Espiratorio Forzado , Estados Unidos/epidemiología , Adulto , Capacidad Vital , Inflamación/fisiopatología , Inflamación/inmunología , Inflamación/diagnóstico , Inflamación/sangre , Mediadores de Inflamación/sangre , Anciano , Biomarcadores/sangre , Factores de Riesgo , Modelos LinealesRESUMEN
Objective: Currently, distinct use of clinical data, routine laboratory indicators or the detection of diabetic autoantibodies in the diagnosis and management of diabetes mellitus is limited. Hence, this study was aimed to screen the indicators, and to establish and validate a multifactorial logistic regression model nomogram for the non-invasive differential prediction of type 1 diabetes mellitus. Methods: Clinical data, routine laboratory indicators, and diabetes autoantibody profiles of diabetic patients admitted between September 2018 and December 2022 were retrospectively analyzed. Logistic regression was used to select the independent influencing factors, and a prediction nomogram based on the multiple logistic regression model was constructed using these independent factors. Moreover, the predictive accuracy and clinical application value of the nomogram were evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). Results: A total of 522 diabetic patients were included in this study. These patients were randomized into training and validation sets in a 7:3 ratio. The predictors screened included age, prealbumin (PA), high-density lipoprotein cholesterol (HDL-C), islet cells autoantibodies (ICA), islets antigen 2 autoantibodies (IA-2A), glutamic acid decarboxylase antibody (GADA), and C-peptide levels. Based on these factors, a multivariate model nomogram was constructed, which had an Area Under Curve (AUC) of 0.966 and 0.961 for the training set and validation set, respectively. Subsequently, the calibration curves demonstrated a strong accuracy of the graph; the DCA and CIC results indicated that the graph could be used as a non-invasive valid predictive tool for the differential diagnosis of type 1 diabetes mellitus, clinically. Conclusion: The established prediction model combining patient's age, PA, HDL-C, ICA, IA-2A, GADA, and C-peptide can assist in differential diagnosis of type 1 diabetes mellitus and type 2 diabetes mellitus and provides a basis for the clinical as well as therapeutic management of the disease.
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Autoanticuerpos , Diabetes Mellitus Tipo 1 , Valor Predictivo de las Pruebas , Humanos , Autoanticuerpos/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Nomogramas , Glutamato Descarboxilasa/inmunología , Adulto Joven , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/inmunología , Curva ROC , Biomarcadores/sangre , Adolescente , AncianoRESUMEN
Background: The correlation between various insulin resistance surrogates and frailty remains under investigation in the scientific community. Methods: Data from NHANES (1999-2018) were used. We utilized weighted binary logistic regression, trend tests, RCS analysis, and subgroup analysis to comprehensively assess the link between METS-IR, HOMA-IR, and TyG, and frailty risk. Results: The results revealed a significant positive association between high levels of METS-IR, HOMA-IR, and TyG with the risk of frailty in all models. Notably, in model 4, the highest quintile of METS-IR showed the strongest link (OR: 2.960, 95% CI: 2.219-3.949), with HOMA-IR (OR: 2.522, 95% CI: 1.927-3.301) following closely behind. Trend tests revealed a positive trend between METS-IR, HOMA-IR, and TyG with the risk of frailty (P for trend < 0.05). RCS analysis showed a linear relationship between METS-IR and the risk of frailty (P for nonlinearity > 0.05). In contrast, HOMA-IR and TyG exhibited a U-shaped nonlinear relationship (P for nonlinearity < 0.05). Conclusion: The research identified a linear association between METS-IR and frailty risk, whereas HOMA-IR and TyG displayed a U-shaped, nonlinear relationship pattern with the risk of frailty. Among the varying levels examined, the linkage between METS-IR and frailty was most pronounced in the top quintile.
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Fragilidad , Resistencia a la Insulina , Encuestas Nutricionales , Humanos , Fragilidad/epidemiología , Fragilidad/sangre , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Anciano , Adulto , Biomarcadores/sangre , Síndrome Metabólico/epidemiología , Glucemia/análisis , Glucemia/metabolismo , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Liver derangement underlies the development of metabolic syndrome in perimenopause. Previously, we have observed that durva swaras (DS) improved metabolic-associated fatty liver disease (MAFLD) and abnormal liver enzymes (aspartate aminotransferase and alanine aminotransferase) along with other complications of menopause in ovariectomized rats. We aimed to decipher the hepatoprotective mechanisms of DS in acetaminophen (APAP)-induced liver injury model, which is analogous to the pathophysiology of MAFLD. MATERIALS AND METHODS: Male Swiss albino mice were distributed into three groups at random. Group I (Control) was administered with vehicle (distilled water) for 7 days. Group II (APAP) received vehicle for the first 6 days and APAP (350 mg/kg - single dose) on the 7th day. Group III (APAP + D) received test compound DS (quality complied) at a dose of 133 mg/kg for 6 days and APAP (350 mg/kg - single dose) on the 7th day. Subsequently, blood and liver tissues were subjected to biochemical, ultrastructural, and gene expression analysis. RESULTS: DS pretreatment protected the liver from APAP-induced disruption of sinusoids and necrosis. DS prevented the elevation of liver enzymes - AST and ALT induced by APAP. Importantly, DS inhibited the APAP-elicited increase in messenger ribonucleic acid levels of hepatic nuclear factor-kappa beta (NF-κB) and pro-inflammatory cytokines, namely interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha. Moreover, DS activated gene expression of nuclear factor erythroid 2-related factor 2 and liver-X-receptor-alpha (LXR-α) to combat the liver damage. CONCLUSION: DS hinders APAP-induced liver damage by activating LXR-α and inhibiting the NF-κB-associated pro-inflammatory cytokine gene expression. These observations confirm the protective role of DS in metabolic dysfunction-associated liver conditions.
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Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Masculino , Ratones , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Acetaminofén/toxicidad , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Modelos Animales de Enfermedad , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Biomarcadores/sangre , Alanina Transaminasa/sangre , FN-kappa B/metabolismo , Citocinas/metabolismo , Aspartato Aminotransferasas/sangre , Inflamación/tratamiento farmacológicoRESUMEN
Blood biomarkers are minimally invasive, are available at a relatively low cost, and are easily accessible; therefore, they are expected to play a pivotal role in the diagnosis of dementia. Measurement of the amyloid-ß ratio and phosphorylated tau in plasma has shown high potential for accurate detection of brain pathology in patients with Alzheimer's disease. Studies have investigated blood biomarkers that reflect neurodegeneration and neuroinflammation in patients with dementia. Challenges associated with blood biomarker use include the lack of robustness of the test and the role of confounders that potentially prevent their immediate clinical application. Further real-world studies are warranted to validate the usefulness of blood biomarkers in dementia management. Appropriate recommendations for the use of blood biomarkers for dementia have been published for physicians and investigators, both in Japan and overseas. Considering the versatility of blood biomarkers, they should be cautiously introduced for clinical use.
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Enfermedad de Alzheimer , Biomarcadores , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/sangre , Humanos , Biomarcadores/sangre , Péptidos beta-Amiloides/sangre , Proteínas tau/sangreRESUMEN
The community population based studies on the relationship between obstructive sleep apnea and liver injury are limited. The study aimed to clarify the association between sleep apnea (SA) and liver injury by using the data in The National Health and Nutrition Examination Survey. SA was assessed by the sleep questionnaire and liver injury was evaluated by liver function test, hepatic steatosis index, and fibrosis-4. Weighted multivariable linear regression was performed to examine the association between SA and liver injury. Subgroup analyses and sensitivity analysis were also conducted. A total of 19,362 eligible participants were included in the study. After adjusting for confounders, the presence of SA was significantly associated with increased levels of lnALT, lnAST/alanine aminotransferase, lnGGT, and lnHSI (all P valuesâ <â .05), but not with lnFIB-4 (Pâ >â .05). There is a dose-response relationship between the severity of SA and increased levels of lnALT, lnGGT, and decreased levels of lnAST/alanine aminotransferase (test for trend, all P valuesâ <â .05). Subgroup analyses revealed that the positive association between SA and liver function, liver steatosis showed a tendency to exist in nonobese, younger, non-Hispanic Black, and male populations. Sensitive analysis showed the relationship between SA and liver injury was stable. Self-reported SA was independently associated with elevated liver enzymes and liver steatosis among US population. The association was more pronounced among nonobese, younger, non-Hispanic Black, and male populations.
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Biomarcadores , Encuestas Nutricionales , Autoinforme , Humanos , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Adulto , Síndromes de la Apnea del Sueño/sangre , Síndromes de la Apnea del Sueño/epidemiología , Alanina Transaminasa/sangre , Pruebas de Función Hepática/métodos , Estados Unidos/epidemiología , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Estudios Transversales , Hígado/lesionesRESUMEN
OBJECTIVES: This study investigated whether kidney transplant donors experience increased arterial stiffness compared with the general population and how arterial stiffness changes over time. MATERIALS AND METHODS: Our study included 59 kidney transplant donors and 27 healthy volunteers. All subjects underwent cardio-ankle vascular index measurements. We studied fibroblast growth factor23, klotho, monocyte chemoattractant protein-1, N-terminal pro-B-type natriuretic peptide, indoxyl sulfate, and p-cresyl sulfate levels. RESULTS: Cardio-ankle vascular index level was higher in donors 6 to 11 years after donation (8.02 ± 0.24 m/s) than in donors 2 to 6 years after donation (7.02 ± 0.27 m/s) and healthy volunteers (6.65 ± 0.22 m/s). Cardioankle vascular index level was positively correlated with age (r = 0.382, P < .001) and levels of triglyceride (r = 0.213, P = .049), blood urea nitrogen (r = 0.263, P = .014), creatinine (r = 0.354, P = .001), calcium (r = 0.228, P = .035), indoxyl sulfate (r = 0.219, P = .042), p-cresyl sulfate (r = 0.676, P ≤ .001), and monocyte chemoattractant protein-1 (r = 0.451, P ≤ .001) and negatively correlated with estimated glomerular filtration rate (r = -0.383, P < .001). Multiple linear regression analysis revealed that age (P = .026, B = 0.244), mean arterial blood pressure (P < .001, B = 0.446), blood urea nitrogen (P = .006, B = 0.302), creatinine (P = .032, B = 0.236), estimated glomerular filtration rate (P = .003, B = -0.323), fibroblast growth factor-23 (P = .007, B = 0.294), N-terminal pro-B-type natriuretic peptide (P = .005, B = 0.304), and monocyte chemoattractant protein-1 (P ≤ .001, B = 0.434) independently predicted cardio-ankle vascular index levels. CONCLUSIONS: Even without additional risk factors, kidney donors should be followed closely for arterial stiffness and cardiovascular disease, especially in the long-term (>5 years) after kidney transplant.
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Biomarcadores , Índice Vascular Cardio-Tobillo , Mediadores de Inflamación , Trasplante de Riñón , Valor Predictivo de las Pruebas , Calcificación Vascular , Rigidez Vascular , Humanos , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Trasplante de Riñón/efectos adversos , Adulto , Estudios de Casos y Controles , Calcificación Vascular/sangre , Calcificación Vascular/fisiopatología , Calcificación Vascular/etiología , Calcificación Vascular/diagnóstico , Factores de Tiempo , Mediadores de Inflamación/sangre , Factores de Riesgo , Factores de Crecimiento de Fibroblastos/sangre , Factor-23 de Crecimiento de Fibroblastos , Quimiocina CCL2/sangre , Uremia/sangre , Uremia/diagnóstico , Uremia/fisiopatología , Indicán/sangre , Resultado del Tratamiento , Donadores VivosRESUMEN
Vitamin D plays a role in inflammatory skin conditions and can improve them. Hidradenitis suppurativa (HS) is an autoinflammatory chronic skin disease in which most patients exhibit a hypovitaminosis D. However, it is uncertain whether vitamin D supplementation could relieve the severity of HS. A systematic literature search of PubMed and Web of Science was conducted on 4 September 2023. Studies that investigated vitamin D and its potential implications for the severity of HS were included. In contrast, studies that focused on the prevalence of vitamin D deficiency were excluded, as well as studies on syndromic HS. Seven studies with a total of 575 patients were included in the qualitative synthesis, of which 3 utilized a cross-sectional design, 2 were pilot studies, 1 a controlled cohort study, and 1 a prospective case-control study. In all included studies, HS patients were vitamin D deficient. There was evidence indicating that serum vitamin D levels negatively correlated with the severity of the disease, and at least suggestive evidence that vitamin D supplementation could have a positive impact on the course of HS. To better understand these correlations, conducting a randomized controlled trial study on vitamin D and its effects on HS severity is imperative.