GDF-15: a novel biomarker of heart failure predicts short-term and long-term heart-failure rehospitalization and short-term mortality in patients with acute heart failure syndrome.

BACKGROUND: Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Growth Differentiation Factor-15 (GDF-15) is a distant member of the transforming growth factor-ß. The increased expression of GDF-15 has been observed during heart failure (HF) and is associated with worse outcomes. However, the relationship between GDF-15 and AHF is not well understood with limited evidence among Thai patients. PURPOSE: Investigate the correlation between biomarker levels (measured upon admission and discharge) and short- and long-term adverse outcomes, encompassing all-cause mortality and heart-failure (HF) rehospitalization (at 30, 90, and 180 days, as well as throughout the entire follow-up duration) in individuals experiencing acute HF. METHODS: This is a prospective single-center investigation involving patients admitted for AHF. Biomarkers, including GDF-15, high-sensitivity troponin T (hsTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were assessed upon admission and discharge. Outcomes, including all-cause mortality and HF rehospitalization, were examined. Logarithmic transformations were applied to the biomarker variables for subsequent analysis. Univariate and multivariate analyses of cause-specific hazards were conducted using the Cox proportional hazards regression model, while subdistribution hazards were assessed using the Fine-Gray regression model to evaluate outcomes. RESULTS: A total of 84 patients were enrolled (mean age of 69 years, 52% females). The GDF-15 level significantly decreased during admission (median at the time of admission 6,346 pg/mL, median at the time of discharge 5,711 pg/mL; p < 0.01). All-cause mortality at 30 days and 180 days were 6.0% and 16.7%, respectively. HF rehospitalization at 30 days and 180 days were 15.5% and 28.6%, respectively. Univariate analysis showed that total orthoedema congestion score (p = 0.02) and admission GDF-15 level (p = 0.01) were associated with 30-day all-cause mortality, whereas hsTnT or NT-proBNP levels did not show significant associations. However, higher levels of NT-proBNP upon admission were associated with all-cause mortality when considering the entire follow-up period (p < 0.01). Both univariate and multivariate analyses demonstrated that lower discharge GDF-15 levels and a greater reduction in GDF-15 levels from admission to discharge were associated with a lower risk of 30-day rehospitalization. Similarly, univariate analysis revealed that a greater reduction in NT-proBNP levels from admission to discharge was associated with lower 30-day rehospitalization rates. At 180 days, a greater reduction in GDF-15 levels remained associated with lower hazards and incidence of rehospitalization. CONCLUSION: The significant decrease in Growth Differentiation Factor-15 (GDF-15) levels during hospitalization suggests its potential as a dynamic marker reflecting the course of AHF. Importantly, higher GDF-15 levels at admission were associated with an increased risk of 30-day all-cause mortality, highlighting its prognostic value in this patient population. Moreover, lower discharge GDF-15 levels, reductions in GDF-15 from admission to discharge, and decreases in NT-proBNP from admission to discharge were associated with a reduced risk of 30-day rehospitalization.

Biomarcadores sanguíneos, de orina y conductas autolesivas e intentos de suicidio repetidos en los adolescentes / Blood and urine biomarkers and repeated self-injurious behaviors and suicide attempts in adolescents

Hay evidencia parcial de que los niveles elevados de la β-endorfina sanguínea se asocian a la adicción suicida en los adultos, pero apenas hay datos sobre los adolescentes. La β-endorfina sanguínea, con un importante papel en los mecanismos de gestión de las adicciones, puede inducir euforia y felicidad, recompensar y reforzar el comportamiento suicida. Para probar si los grandes repetidores de intentos de suicidio (5 o más intentos de suicidio) y de conductas autolesivas (20 o más episodios de autolesiones) tienen unos niveles de biomarcadores más elevados, se selecciona una muestra de 43 pacientes de entre 12 y 17 años que acuden al Servicio de Urgencias Psiquiátricas en el Hospital Universitario Puerta de Hierro Majadahonda. Diez presentan 5 o más intentos de suicidio, 35 presentan 20 o más episodios autolesivos y 10 presentan ambas características, y la mayoría de los adolescentes cumplían criterios de adicción para autolesiones y suicidio. Los resultados sugieren que todos los pacientes que presentaban adicción al suicidio también presentaban adicción a la autolesión. Los niveles de ACTH, cortisol y β-endorfina sanguíneos y de cortisol en orina fueron muy elevados, pero no diferenciaban a los grandes repetidores del resto de adolescentes. (AU)

There is partial evidence that elevated levels of blood β-endorphin are associated with suicidal addiction in adults, but hardly any data on adolescents. Blood β-endorphin, with an important role in addiction management mechanisms, can induce euphoria and happiness, reward and reinforce suicidal behavior. To test whether high repeaters of suicide attempts (5 or more suicide attempts) and self-injurious behaviors (20 or more episodes of self-injury) have higher biomarker levels, a sample of 43 patients aged 12-17 years attending the Psychiatric Emergency Department at the Hospital Universitario Puerta de Hierro Majadahonda is recruited. Ten present 5 or more suicide attempts, 35 present 20 or more self-injurious episodes and 10 present both characteristics, and most of the adolescents meet addiction criteria for self-injury and suicide. The results suggest that all patients with addiction to suicide also had addiction to self-injury. Blood ACTH, cortisol and β-endorphin and urine cortisol levels were very elevated, but did not differentiate heavy repeaters from the rest of the adolescents. (AU)

Development of fatty acid metabolism score based on gene signature for predicting prognosis and immunotherapy response in colon cancer

Purpose Metabolic reprogramming is a novel hallmark and therapeutic target of cancer. Our study aimed to establish fatty acid metabolism-associated scores based on gene signature and investigated its effects on immunotherapy in colon cancer. Methods Gene expression and clinical information were collected from Gene Expression Omnibus (GEO) database to identify a gene signature by non-negative matrix factorization (NMF) clustering and Cox regression analysis. Subsequently, we constructed the fatty acid metabolism score (FA-score) model by principal component analysis (PCA) and explored its relativity of prognosis and the response to immunotherapy in colon cancer. Finally, the Cancer Genome Atlas (TCGA) database was introduced and in vitro study was performed for verification. Results The FA-score-high group had a higher level of fatty acid metabolism and was associated with worse patient overall survival. Significantly, FA-score correlated closely with the biomarkers of immunotherapy, and the FA-score-high group had a poorer therapeutic efficacy of immune checkpoint blockade. In vitro experiments demonstrated that ACSL5 may be a critical metabolic regulatory target. Conclusions Our study provided a comprehensive analysis of the heterogeneity of fatty acid metabolism in colon cancer. We highlighted the potential clinical utility of fatty acid metabolism-related genes to be biomarkers of colon cancer prognosis and targets to improve the effect of immunotherapy (AU)

Genome-wide characterization of circulating metabolic biomarkers.

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.

How we use angiopoietin-2 in the diagnosis and management of vascular anomalies.

The diagnosis of vascular anomalies remains challenging due to significant clinical heterogeneity and uncertain etiology. Evaluation using biopsy and/or genetic testing for somatic variants is invasive, expensive, and prone to sampling error. There is great need for noninvasive and easily measured blood laboratory biomarkers that can aid not only in diagnosis, but also management of treatments for vascular anomalies. Angiopoietin-2, a circulating blood angiogenic factor, is highly elevated in patients with kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon and kaposiform lymphangiomatosis. Here, we describe our clinical experience using serum angiopoietin-2 as a biomarker for diagnosis and monitoring response to treatment.

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis.

Introduction: We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. Methods: We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. Results: There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Conclusion: Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.

Utilidad de la región medial de la pro-adrenomodulina para la detección de bacteriemia verdadera en pacientes mayores atendidos en urgencias por sospecha de infección / Utility of the medial region of pro-adrenomodulin for the detection of true bacteremia in elderly patients treated in the emergency department for suspected infection

Introducción. La predicción de bacteriemia en urgencias es importante para la toma de decisiones iniciales. La población mayor un reto diagnóstico. El objetivo fue evaluar la capacidad de la región medial de la pro-adrenomodulina (MR-proADM) para identificar bacteriemia verdadera (BV) en pacientes mayores atendidos en tres servicios de urgencias. Metodología. Estudio observacional incluyendo pacientes ≥75 años atendidos por sospecha de infección en los que se extrajo un hemocultivo (HC). Se recogieron variables sociodemográficas, comorbilidad, hemodinámicas, analíticas y biomarcadores [MR-proADM, procalcitonina (PCT), proteína C reactiva (PCR) y lactato]. La variable de resultado fue un verdadero positivo en el hemocultivo. Resultados. Se incluyeron 109 pacientes con edad media de 83 (DE 5,5) años. En 22 pacientes (20,2%) se obtuvo un diagnóstico final de BV. Las variables independientes para predecirla fueron PCT (OR13,9; IC95%: 2,702-71,703; p=0,002), MR-proADM (OR4,081; IC95%: 1,026-16,225; p=0,046) y temperatura (OR 2,171; IC95%: 1,109-4,248; p=0,024). Considerando el punto de corte con mayor rendimiento diagnóstico para el MR-proADM (2,13 mg/dl), se obtuvo una sensibilidad (Se) de 73%, una especificidad (E) de 71%, un valor predictivo positivo (VPP) de 39%, un valor predictivo negativo (VPN) de 91%, un coeficiente de verosimilitud positivo (LHR+) de 2,53 y un coeficiente de verosimilitud negativo (LHR-) de 0,38; para PCT (0,76 mg/dl) se obtuvo una Se de 90%, E de 65%, VPP de 40%, VPN de 96%, LHR+ 2,64 y un LHR– de 0,14. Al combinar ambos, se observó una Se de 69%, E de 84%, VPP de 52%, VPN de 91%, LHR+ de 4,24 y un LHR- de 0,38. Conclusión. Niveles elevados de PCT y MR-proADM se asocian a un riesgo incrementado de BV y la combinación de ambos mejora la capacidad para identificar estos pacientes. (AU)

Background. The prediction of bacteremia in the emergency department (ER) is important for initial decision-making. The elderly population is a diagnosis challenge. The objective was to evaluate the accuracy of mid regional pro-adrenomedullin (MR-proADM) to identify true bacteremia (BV) in elderly patients attended in 3 hospital emergency departments. Methods. Observational study including patients ≥75 years of age or older attended in the ER for suspected infection in whom a blood culture (BC) was extracted. Sociodemographic, comorbidity, hemodynamic and analytical variables, biomarkers [MR-proADM, procalcitonin (PCT), C-reactive protein (CRP) and lactate] and final diagnosis were collected. The primary outcome was a true positive on a blood culture. Results. A total of 109 patients with a mean age of 83 (SD: 5.5) years were included. A final diagnosis of BV was obtained in 22 patients (20.2%). The independent variables to predict it were PCT (OR: 13.9; CI95%: 2.702-71.703; p=0.002), MR-proADM (OR: 4.081; CI95%: 1.026-16.225; p=0.046) and temperature (OR: 2.171; CI95%: 1.109-4.248; p=0.024). Considering the cut-off point for MR-proADM (2.13 mg/dl), a sensitivity (Se) of 73%, specificity (E) of 71%, a positive predictive value (PPV) of 39%, a negative predictive value (NPV) of 91%, a positive likelihood ratio (LHR+) of 2.53 and a negative likelihood ratio (LHR-) of 0.38; for PCT (0.76 mg/dl) a Se of 90%, E of 65%, PPV of 40%, NPV of 96%, LHR+ 2,64 and a LHR- of 0.14 were obtained. When combining both, a Se of 69%, E of 84%, PPV of 52%, NPV of 91%, LHR+ of 4.24 and LHR- of 0.38 were observed. Conclusions. Elevated levels of PCT and MR-proADM were independently associated with an increased risk of BV and the combination of both improves the accuracy to identify these patients. (AU)

Brain-Derived neurotrophic factor and inflammatory biomarkers are unaffected by acute and chronic intermittent hypoxic-hyperoxic exposure in geriatric patients: a randomized controlled trial.

BACKGROUND: Animal and human studies have shown that exposure to hypoxia can increase brain-derived neurotrophic factor (BDNF) protein transcription and reduce systematic inflammatory cytokine response. Therefore, the aim of this study was to investigate the acute and chronic effects of intermittent hypoxic-hyperoxic exposure (IHHE) prior to aerobic exercise on BDNF, interleukin-6 (IL-6), and C-reactive protein (CRP) blood levels in geriatric patients. PATIENTS AND METHODS: Twenty-five geriatric patients (83.1 ± 5.0 yrs, 71.1 ± 10.0 kg, 1.8 ± 0.9 m) participated in a placebo-controlled, single-blinded trial and were randomly assigned to either an intervention (IG) or control group (CG) performing an aerobic cycling training (17 sessions, 20 min·session-1, 3 sessions·week-1). Prior to aerobic cycling exercise, the IG was additionally exposed to IHHE for 30 min, whereas the CG received continuous normoxic air. Blood samples were taken immediately before (pre-exercise) and 10 min (post-exercise) after the first session as well as 48 h (post-training) after the last session to determine serum (BDNFS) and plasma BDNF (BDNFP), IL-6, and CRP levels. Intervention effects were analyzed using a 2 x 2 analysis of covariance with repeated measures. Results were interpreted based on effect sizes with a medium effect considered as meaningful (ηp2 ≥ 0.06, d ≥ 0.5). RESULTS: CRP was moderately higher (d = 0.51) in the CG compared to the IG at baseline. IHHE had no acute effect on BDNFS (ηp2 = 0.01), BDNFP (ηp2 < 0.01), BDNF serum/plasma-ratio (ηp2 < 0.01), IL-6 (ηp2 < 0.01), or CRP (ηp2 = 0.04). After the 6-week intervention, an interaction was found for BDNF serum/plasma-ratio (ηp2 = 0.06) but not for BDNFS (ηp2 = 0.04), BDNFP (ηp2 < 0.01), IL-6 (ηp2 < 0.01), or CRP (ηp2 < 0.01). BDNF serum/plasma-ratio increased from pre-exercise to post-training (d = 0.67) in the CG compared to the IG (d = 0.51). A main effect of time was found for BDNFP (ηp2 = 0.09) but not for BDNFS (ηp2 = 0.02). Within-group post-hoc analyses revealed a training-related reduction in BDNFP in the IG and CG by 46.1% (d = 0.73) and 24.7% (d = 0.57), respectively. CONCLUSION: The addition of 30 min IHHE prior to 20 min aerobic cycling seems not to be effective to increase BDNFS and BDNFP or to reduce IL-6 and CRP levels in geriatric patients after a 6-week intervention.The study was retrospectively registered at drks.de (DRKS-ID: DRKS00025130).

Plasma biomarkers of Alzheimer's disease and related dementias in American Indians: The Strong Heart Study.

INTRODUCTION: Identification of Alzheimer's disease (AD) needs inexpensive, noninvasive biomarkers, with validation in all populations. METHODS: We collected plasma markers in older American Indian individuals: phosphorylated-tau181 (pTau181); amyloid-beta (Aß) 40,42; glial fibrillary acidic protein (GFAP); and neurofilament light chain (NfL). Plasma markers were analyzed for discriminant properties with cognitive status and etiology using receiver operating characteristic (ROC) analysis. RESULTS: PTau181, GFAP, NfL plasma values were significantly associated with cognition, but Aß were not. Discriminant performance was moderate for individual markers, with pTau181, GFAP, NfL performing best, but an empirically selected panel of markers (age, sex, education, pTau181, GFAP, NfL, Aß4240 ratio) had excellent discriminant performance (AUC > 0.8). DISCUSSION: In American Indian individuals, pTau181 and Aß values suggested more common pathology than in majority populations. Aß was less informative than in other populations; however, all four markers were needed for a best-performing dementia diagnostic model. These data validate utility of AD plasma markers, while suggesting population-specific diagnostic characteristics.

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome / Anticuerpos contra las células parietales como biomarcadores potenciales de enfermedad pulmonar intersticial relacionada con el síndrome de Sjögren primario

Background ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. Methods Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. Results A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). Conclusion APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS (AU)

Antecedentes La enfermedad pulmonar intersticial (EPI) es una manifestación común del síndrome de Sjögren primario (SSp) y está relacionada con un mayor riesgo de muerte. Los anticuerpos anticélulas parietales (AACP) están fuertemente expresados por células epiteliales alveolares proliferantes en los pulmones fibróticos y están relacionados con la disminución acelerada de la función pulmonar en la gibrosis pulmonar idiopática. En este estudio, pretendemos evaluar la aplicación clínica de la AACP en pacientes con EPI con SSp. Método Se revisaron los datos clínicos, de laboratorio, de función pulmonar e imágenes de los pacientes con SSp y se utilizó la ESSDAI para evaluar la actividad de la enfermedad en general. Se registraron 5 características principales de imagen pulmonar de la EPI y 2 radiólogos ciegos experimentados realizaron una puntuación semicuantitativa de HRCT de forma independiente. Comparamos las características clínicas de los pacientes con y sin EPI con SSp y realizamos un análisis de regresión logística de los factores de riesgo de EPI en SSp. Resultados Un total de 74 pacientes con SSp y 40 controles sanos fueron incluidos en el estudio. La EPI es más común en el grupo positivo de AACP que en el grupo negativo de APCA. El nivel cuantitativo de AACP, está positivamente relacionado con la puntuación de imagen. El análisis multifactorial encontró que la larga duración, el aumento de los niveles de AACP y el aumento de los niveles de KL-6 fueron factores de riesgo independientes para la EPI en pacientes con SSp. El área bajo la curva ROC de AACP es de 0,6618 y la concentración umbral fue de 153,82 ng/ml (sensibilidad 45,24% y especificidad 87,50%). Conclusiones Los niveles de AACP son un factor de riesgo independiente y pueden ser biomarcadores potenciales de EPI en pacientes con SSp (AU)

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.

Persistently High Procalcitonin and C-Reactive Protein Are Good Predictors of Infection in Acute Necrotizing Pancreatitis: A Systematic Review and Meta-Analysis.

Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic therapy can save patients' lives. We systematically searched three databases on 27 October 2022. In the eligible studies, the presence of infection in necrotizing pancreatitis was confirmed via a reference test, which involved either the identification of gas within the necrotic collection through computed tomography imaging or the examination of collected samples, which yielded positive results in Gram staining or culture. Laboratory biomarkers compared between sterile necrotizing pancreatitis and INP were used as the index test, and our outcome measures included sensitivity, specificity, the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval (CI): 0.62-0.76), for procalcitonin (PCT), it was 0.69 (CI: 0.60-0.78), and for white blood cell count, it was 0.61 (CI: 0.47-0.75). After the first 72 h, the pooled AUC of CRP showed an elevated level of 0.88 (CI: 0.75-1.00), and for PCT, it was 0.86 (CI: 0.60-1.11). The predictive value of CRP and PCT for infection is poor within 72 h after hospital admission but seems good after the first 72 h. Based on these results, infection is likely in case of persistently high CRP and PCT, and antibiotic initiation may be recommended.

Circulating Monocyte Chemoattractant Protein-1 (MCP-1) in Patients with Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that leads to the destruction of the intrahepatic bile ducts. While the inflammatory process can be mediated by monocyte chemotactic protein-1 (MCP-1), the importance of circulating MCP-1 as a biomarker is unclear. Our aim was to assess the diagnostic significance of the serum concentrations of MCP-1 in PBC patients. We compared circulating MCP-1 with biochemical, immunological and histological parameters. Serum samples were collected from 120 PBC patients, 60 pathologic controls and 30 healthy donors. MCP-1 levels were determined by using commercial enzyme-linked immunosorbent assay (ELISA). Elevated serum MCP-1 levels were detected in 66% of PBC patients with a specificity of 97%. Significantly higher levels of MCP-1 protein were found in the sera of patients with PBC than in the group of healthy individuals-410.2 pg/mL vs. 176.0 pg/mL, p < 0.01). Patients with higher concentrations of alkaline phosphatase also had higher levels of MCP-1 (r = 0.4, p < 0.01). In accordance with Ludwig's classification, a positive correlation of serum MCP-1 concentration with the degree of fibrosis was observed, OR = 6.1, p = 0.0003. We compared the MCP-1 with procollagen type III, hyaluronic acid (HA), FIB-4 index, APRI and collagen type IV when predicting the advance of liver fibrosis. Circulating MCP-1 is better correlated with liver fibrosis and is also associated with the occurrence of specific antimitochondrial autoantibodies and specific anti-nuclear autoantibodies-anti-gp210. MPC-1 can be considered to be a tool for diagnosing the degree of fibrosis in PBC, and combinations of MCP-1 and other specific biomarkers could support the diagnosis of PBC.

The relationship between alterations in plasma metabolites and treatment responses in antipsychotic-naïve female patients with schizophrenia.

This study aimed to explore the relationship between alterations in plasma metabolites and treatment responses amongst antipsychotic-naïve female patients with schizophrenia. A total of 38 antipsychotic-naïve female schizophrenia patients (ANS) and 19 healthy female controls (HC) were recruited. Plasma samples were obtained from all participants, and targeted metabolomics were measured with FIA-MS/MS and LC-MS/MS. The positive and negative syndrome scale (PANSS) was used to assess the severity of psychotic symptoms before and after eight weeks of treatment. Receiver operator characteristics (ROC) curves were used to predict diagnostic and therapeutic responses. A total of 186 metabolites passed quality control procedures and were used in statistical analysis to identify potential biomarkers. Before treatment, the ANS patients had lower levels of γ -Aminobutyric Acid (GABA) and higher levels of Cholesteryl esters (CE) (20:3), Cholic Acid (CA) and Glycocholic Acid (GCA) compared to the HCs. These four differential metabonomic markers were synthesised into a combinatorial biomarker panel. This panel significantly distinguished ANS from HC. Moreover, this biomarker panel was able to effectively predict therapeutic responses. Our results suggest that plasma CE (20:3), CA, GCA, and GABA levels may be useful for diagnosing and predicting antipsychotic efficacy amongst female schizophrenia patients.

Beneficial effects of coconut oil (Cocos nucifera) on hematobiochemicl and histopathological markers in CCL4-intoxicated rabbits / Efeitos benéficos do óleo de coco (Cocos nucifera) em marcadores hematobioquímicos e histopatológicos em coelhos intoxicados com CCL4

The study was designed to investigate the effect of Coconut Oil on the levels of some liver and hematological parameters in carbon tetrachloride intoxicated rabbits. Also the antioxidant capacity of Coconut Oil for various concentrations was assessed on the basis of percent scavenging of (DPPH) free radical. Experimental animals were divided into five groups, eight rabbits in each group. These were: group A (Normal control), group B (Toxic control), group C (Standard control), group D (Treated with Coconut Oil 50 mL/kg body weight after CCl4 intoxication), group E (Treated with Coconut Oil 200 mL/kg body weight after CCl4 intoxication). The effects observed were compared with a standard hepatoprotective drug silymarine (50 mL/kg body weight). The Coconut Oil (200 mL/kg body weight) significantly (P<0.05) reduced the elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) when compared to a toxic control rabbits. The results of extract treated rabbits were similar to silymarine administered rabbits group. Treatment with Coconut Oil root and silymarine caused no significant changes in RBC, Platelets, (Hb), (MCH) concentration and (HCT) values. However, significant (P<0.05) increase was observed in the total WBC count. The present study suggested that Coconut Oil can be used as an herbal alternative (need further exploration i.e to detect its bioactive compound and its efficacy) for hepatoprotective activit.

O estudo foi desenhado para investigar o efeito do óleo de coco nos níveis de alguns parâmetros hepáticos e hematológicos em coelhos intoxicados com tetracloreto de carbono. Também a capacidade antioxidante do óleo de coco para várias concentrações foi avaliada com base na porcentagem de eliminação de radicais livres (DPPH). Os animais experimentais foram divididos em cinco grupos, oito coelhos em cada grupo. Estes foram: grupo A (controle normal), grupo B (controle tóxico), grupo C (controle padrão), grupo D (tratado com óleo de coco 50 mL/kg de peso corporal após intoxicação por CCl4), grupo E (tratado com óleo de coco 200 mL/kg de peso corporal após intoxicação por CCl4). Os efeitos observados foram comparados com um fármaco hepatoprotetor padrão silimarina (50 mL/kg de peso corporal). O óleo de coco (200 mL/kg de peso corporal) reduziu significativamente (P<0,05) os níveis séricos elevados de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP), quando comparado a um coelho controle tóxico. Os resultados dos coelhos tratados com extrato foram semelhantes aos do grupo de coelhos administrados com silimarina. O tratamento com raiz de óleo de coco e silimarina não causou alterações significativas nos valores de RBC, Plaquetas, (Hb), (MCH) e (HCT). No entanto, observou-se aumento significativo (P<0,05) na contagem total de leucócitos. O presente estudo sugeriu que o óleo de coco pode ser usado como uma alternativa fitoterápica (precisa de mais exploração, ou seja, para detectar seu composto bioativo e sua eficácia) para atividade hepatoprotetora.

Maternal serum fatty acid binding protein-4 level is upregulated in fetal growth restriction with abnormal Doppler flow patterns.

PURPOSE: This study aimed to determine fatty acid binding protein-4 (FABP-4) concentrations in maternal serum of fetal growth restriction (FGR) pregnancies and controls of normal pregnancies. Furthermore, we hypothesized that the alterations in FABP-4 levels might correlate with FGR severity. METHODS: We performed this prospective case-control study with 83 pregnant women. The study groups included 26 FGR pregnancies without abnormal fetal Doppler flow patterns and 25 pregnancies complicated with FGR accompanied by abnormal fetal Doppler flow patterns. RESULTS: The median serum FABP-4 concentrations were significantly higher in the FGR cases with abnormal Doppler flow pattern group (2.09 ng/mL) than in the FGR cases without abnormal Doppler flow pattern group (1.62 ng/mL) and the control group (1.20 ng/mL, p < 0.001). A significant negative correlation was observed between maternal serum FABP-4 levels and time to birth from blood sample collection (r = -0.356 and p = 0.001), gestational week at birth (r = -0.386 and p < 0.001), and birth weight (r = -0.394 and p < 0.001). A 1.35 ng/mL cut-off value of serum FABP-4 level could be used to discriminate FGR cases with a 78.4% sensitivity and 60.6% specificity. The optimal cut-off value of FABP-4 levels as an indicator for the diagnosis of FGR with abnormal Doppler flow pattern was estimated to be 1.76 ng/mL, which yielded a sensitivity of 84.0% and a specificity of 75.8%. CONCLUSION: FABP-4 is a crucial biomarker in the diagnosis and determining the severity of pregnancies with restricted fetal growth. We consider that FABP-4 is a powerful, reliable, and unique biomarker to diagnose FGR pregnancies.

YKL-40 as a biomarker in various inflammatory diseases: A review.

YKL-40 or Chitinase-3-Like Protein 1 (CHI3L1) is a highly conserved glycoprotein that binds heparin and chitin in a non-enzymatic manner. It is a member of the chitinase protein family 18, subfamily A, and unlike true chitinases, YKL-40 is a chitinase-like protein without enzymatic activity for chitin. Although its accurate function is yet unknown, the pattern of its expression in the normal and disease states suggests its possible engagement in apoptosis, inflammation and remodeling or degradation of the extracellular matrix. During an inflammatory response, YKL-40 is involved in a complicated interaction between host and bacteria, both promoting and attenuating immune response and potentially being served as an autoantigen in a vicious circle of autoimmunity. Based on its pathophysiology and mechanism of action, the aim of this review was to summarize research on the growing role of YKL-40 as a persuasive biomarker for inflammatory diseases' early diagnosis, prediction and follow-up (e.g., cardiovascular, gastrointestinal, endocrinological, immunological, musculoskeletal, neurological, respiratory, urinary, infectious) with detailed structural and functional background of YKL-40.

Organ aging signatures in the plasma proteome track health and disease.

Animal studies show aging varies between individuals as well as between organs within an individual1-4, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan. We discovered nearly 20% of the population show strongly accelerated age in one organ and 1.7% are multi-organ agers. Accelerated organ aging confers 20-50% higher mortality risk, and organ-specific diseases relate to faster aging of those organs. We find individuals with accelerated heart aging have a 250% increased heart failure risk and accelerated brain and vascular aging predict Alzheimer's disease (AD) progression independently from and as strongly as plasma pTau-181 (ref. 5), the current best blood-based biomarker for AD. Our models link vascular calcification, extracellular matrix alterations and synaptic protein shedding to early cognitive decline. We introduce a simple and interpretable method to study organ aging using plasma proteomics data, predicting diseases and aging effects.