Plasma Markers Research Articles

Subcortical tau burden correlates with regional brain atrophy and plasma markers in four-repeat tauopathy parkinsonism

Background 18F-florzolotau positron emission tomography (PET) assists in the in vivo diagnosis of progressive supranuclear palsy (PSP). Objective We aimed to investigate the relationship between 18F-florzolotau uptake and clinical severity, structural volume changes, and plasma markers in four-repeat tauopathies. Methods A total of 80 participants were recruited: 35 with PSP (11 with PSP-Richardson syndrome and 24 with PSP non-Richardson syndrome), 9 with corticobasal syndrome (CBS), 10 with Alzheimer's disease (AD), 8 with Parkinson's disease, and 18 controls. All participants underwent 18F-florzolotau PET, brain magnetic resonance imaging (MRI), and plasma biomarker investigation (total and phosphorylated tau [pTau181], neurofilament light chain, and glial fibrillary acidic protein [GFAP]). Results 18F-Florzolotau uptake was significantly higher in the subcortical regions of the pallidum, subthalamic nucleus (STN), midbrain, red nucleus, and raphe nucleus in PSP patients compared to the other groups (all p < 0.01). Subcortical tau tracer retention assisted in distinguishing PSP and CBS from controls (AUC = 0.836, p < 0.001). Tau tracer retention could differentiate PSP and CBS from AD in cortical ( p < 0.001) and subcortical regions ( p = 0.028). The motor severity of PSP positively correlated with tau burden in STN ( p = 0.044) and substantia nigra ( p = 0.035). Tau tracer uptake was associated with cortical volume changes in CBS ( p = 0.031), PSP non-Richardson syndrome ( p = 0.003), and AD ( p = 0.044). Cortical tau retention correlated with plasma levels of GFAP ( p = 0.001) and pTau181 ( p = 0.036). Conclusions Subcortical 18F-Florzolotau uptake assist the diagnosis of 4R tauopathy parkinsonism. Additionally, regional tau burden contributes to structural brain volume changes and correlates with plasma levels of GFAP and pTau181.

Dietary Bovine Lactoferrin Reduces the Deleterious Effects of Lipopolysaccharide Injection on Mice Intestine.

Injection of lipopolysaccharides (LPS) in experimental models induces a systemic inflammatory response that is associated with deleterious effects on intestinal morphology and physiology. In this study, we have studied in female mice the effects of dietary supplementation with bovine lactoferrin (bLF) given before intraperitoneal injection of LPS on jejunum and colon. The first study evaluated the efficiency of different bLF and LPS concentrations to determine the optimal experimental conditions. For the second study mice were fed with 1% bLF before the LPS challenge (3 mg/kg body weight). Plasmatic markers of inflammation, intestinal morphology, permeability, and expression of genes related to epithelial differentiation, epithelial barrier function and intestinal inflammation in both small intestine and colon were evaluated. bLF ingestion before the LPS challenge reduced the TNF-α circulating concentration, compared to control animals. This decrease in plasma TNF-α was correlated with improved intestinal permeability. The morphology of jejunal epithelium, which was affected by LPS challenge, was partly maintained by bLF. Measurement of the expression of genes encoding proteins involved in epithelial differentiation, intestinal inflammation, and epithelial barrier function suggests an overall protective effect of bLF against the adverse effects of LPS in the jejunum. In the colon, the effects of bLF ingestion on the subsequent LPS challenge, although protective, remain different when compared with those observed on jejunum. Taken together, our data indicate that bLF dietary supplementation does have a protective effect on the deleterious intestinal alterations induced by LPS systemic inflammation.

Effects of long-term almond consumption on markers for vascular function and cardiometabolic risk in men and women with prediabetes: results of a randomized, controlled cross-over trial.

The aim of this study was to investigate the long-term effects of almond consumption on peripheral vascular function, ambulant blood pressure profiles (ABP), and serum/plasma markers reflecting endothelial dysfunction and inflammation in participants with overweight/obesity and prediabetes. Thirty-four participants completed this single-blinded, randomized, cross-over trial with 5-month intervention and control periods, separated by a 2-month wash-out. During the intervention period, participants consumed 50g of whole almonds daily. At the end of each intervention period, peripheral vascular function was assessed by measuring the carotid-to-femoral and carotid-to-radial pulse wave velocities (PWVc-f and PWVc-r, respectively) and retinal microvascular calibers. Serum/plasma concentrations of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNFα), serum amyloid A protein (SAA) and high-sensitivity C-reactive protein (hs-CRP) and 24-hour ABP were also analyzed. Almond consumption did not significantly affect arterial stiffness (PWVc-f and PWVc-r), while central retinal venular equivalent (CRVE) was minimally increased by 2μm (P = 0.019). Central retinal arteriolar equivalent (CRAE), the arteriolar-to-venular ratio (AVR), and endothelial and inflammatory serum/plasma markers showed no significant changes after almond consumption. Almond consumption reduced systolic blood pressure (SBP; -3 mmHg 24-hour P = 0.035, -4 mmHg daytime P = 0.046, and - 4 mmHg during nighttime P = 0.029), SBP variability during 24-hour, daytime, and nighttime (P = 0.005, P = 0.019, and P = 0.003, respectively), and diastolic blood pressure variability during nighttime (P ≤ 0.001). Almond consumption did not affect arterial stiffness, retinal microvasculature calibers, or serum and plasma markers for endothelial dysfunction and inflammation in participants with prediabetics, while BP and BP variability were improved. This clinical trial was registered in February 2018 as NCT03419702.

A triad of gut dysbiosis, dysregulated immunity, and ‘leaky’ gut characterize HCMV associated neonatal cholestasis

BackgroundGut microbiome dysbiosis and related immune dysfunction have been associated with the pathogenesis of Human Cytomegalovirus (HCMV) infection in infants with neonatal cholestasis (NC) as previously reported by us. However, the interaction of a perturbed microbiome, HCMV infection, and dysregulated immunity leading to exacerbation of disease severity has not been investigated so far. In this study, we examined the association of gut microbiome, host inflammatory and homeostatic markers that are likely to govern increased pathogenesis of NC in HCMV infected IgM positive infants (N = 15) compared to IgM negative (N = 15) individuals. Stool samples of HCMV infected infants and age-matched healthy controls (N = 10) were assessed for gut bacteria-derived metabolites like short-chain fatty acids (SCFAs), Lipopolysaccharide (LPS), cytokines and markers of gut barrier integrity. Data were correlated with previously determined gut microbiome composition and frequency of immune cell subsets. Finally, validation of clinical potential was undertaken by principal component analysis (PCA) of integrated data to delineate the spectrum of clinical pathology. ResultsSignificantly lower levels of SCFAs and elevated fecal levels of soluble inflammatory mediators were observed in IgM positive HCMV infected infants. Further, increased plasma LPS levels and markers of gut permeability, suggestive of microbial translocation due to a ‘leaky gut’ were observed in HCMV infected IgM positive group. PCA of integrated data revealed clearly disparate profiles representative of IgM positive, IgM negative, and uninfected healthy states. ConclusionOur results suggest the utility of an integrated approach involving dysregulated microbiome-immune axis for gaining a better understanding of pathogenesis associated with HCMV infection in NC.Graphical

Associations Between Plasma Levels of NLRP3 Protein, Interleukin-1 Beta and Features of Acute ST-Elevation Myocardial Infarction.

Phenotyping inflammation in ST-elevation myocardial infarction (STEMI) is a challenge for modern cardiology. NLRP3 inflammasome is a proven predictor of adverse outcomes in cardiovascular disease, but its specificity in stratifying inflammatory activity in patients with myocardial infarction (MI) has not been demonstrated. The aim of this paper is to describe the levels of NLRP3 protein and IL-1β concentrations and their changes in dynamics and associations with clinical, laboratory and instrumental characteristics of patients with STEMI. A total of 45 patients with STEMI were enrolled. Concentrations of NLRP3 and IL-1β were evaluated in arterial and venous EDTA blood from the infarct-related coronary and peripheral arteries and veins on days 1, 3 and 7 after MI. The concentrations of markers were higher on the first day after MI with a maximum decrease on the third day. The levels of both markers in venous plasma correlated with those in arterial blood, allowing their routine determination in venous plasma on the first day after MI. IL-1β levels correlated directly with the wall motion index and inversely with left ventricular ejection fraction and stroke volume, which characterize the potential contribution to adverse myocardial remodeling. There were two multidirectional trends in changes in NLRP3 and IL-1β levels during hospitalization. Initially higher levels with a gradual decrease by day 7 were associated with a longer duration of myocardial ischemia and higher plasma troponin I levels. Further evaluation of the long-term outcomes of MI will allow identifying inflammatory factors that input to the development of secondary major adverse cardiac events and will provide a new step in the understanding of inflammatory phenotyping.

Proteomic Insights Into Gingival Crevicular Extracellular Vesicles in Periodontitis and Gestational Diabetes: An Exploratory Study.

To characterize the gingival crevicular fluid (GCF) and plasma extracellular vesicles (EVs) and explore their proteomic cargo in healthy pregnant women compared to those with gestational diabetes mellitus (GDM) and periodontitis. One-hundred and four pregnant women were recruited at 24-30 gestation weeks. GDM was diagnosed by an oral glucose tolerance test. GCF and plasma samples were obtained to isolate EVs and characterized by nanoparticle tracking, immunoassays, electron microscopy and mass spectrometry. Of the recruits,17.3% women were healthy, 50% had periodontitis and 32.7% had both GDM and periodontitis. Probing depth, clinical attachment loss and bleeding on probing were more severe in GDM and periodontitis pregnancies (p < 0.0001). Additionally, this group showed an increase concentration of total, small and large GCF-EVs (p = 0.0015, p = 0.0011 and p = 0.0008, respectively), with decreased expression of CD9, CD81 and CD81/CD63 ratio (p = 0.0461, p = 0.0164 and p = 0.0005, respectively). No differences were observed in plasmatic EVs concentration or markers expression. Proteomic analysis of GCF-EVs showed peptides of both host and bacterial origin. Gene ontology analysis revealed that proteins of GCF-EVs participate in immune inflammatory responses, glucose metabolism and insulin response mechanisms. GCF-EVs were increased in both GDM and periodontitis, and their proteomic cargo suggest their involvement in immune inflammatory response, glucose metabolism and insulin pathways during pregnancy.

Probiotics' supplementation alleviates disease severity and improves postural balance by repairing intestinal leak in patients suffering from osteoarthritis: a double-blinded clinical trial.

Increased intestinal leakiness and associated systemic inflammation are potential contributors to osteoarthritis (OA) and postural imbalance in the geriatric population. To date, no successful treatment to correct postural imbalance in OA is known. We aimed to explore the effects of a multistrain probiotic upon postural imbalance in OA-affected patients. In this randomised, double-blind trial with a placebo group, 147 patients suffering from knee OA (age span = 64-75 years) were divided into placebo (n 75) and probiotics (n 72) study groups. Vivomix 112 billion, multistrain probiotic was given once a day for 12 weeks. The outcomes of study variables were determined first at baseline and later after 12 weeks of intervention. These were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee flexion range of motion (ROM), pain intensity by visual analogue scale, handgrip strength (HGS), gait speed and balance control assessed in standing, semi-tandem and tandem stances. We determined plasma zonulin to determine intestinal leak along with c-reactive protein and 8-isoprostanes levels. A total of 136 OA patients taking placebo (n 71) and probiotics (n 65) were analysed. The probiotics group exhibited a reduction in pain intensity, disease severity and WOMAC scores along with improvement in balance scores, HGS and walking speed (P < 0·05 for all), no change in ROM, resting pain and 8-isoprostanes levels. The correlation analysis revealed a robust association of balance scores with plasma markers of intestinal leakiness and inflammation in probiotics but not in the placebo group. Probiotics reduce postural imbalance in OA patients partly due to a reduction in intestinal leakiness.

Ginger Extract Improves Cognitive Dysfunction via Modulation of Gut Microbiota-Derived Short-Chain Fatty Acids in D-Galactose/Ovariectomy-Induced Alzheimer-Like Disease.

Alzheimer's disease (AD) is the most common form of dementia with complex causes and limited treatment options. Recent research has suggested a connection between the progression of AD and the activity of gut microbiota. Ginger, a plant known for its anti-inflammatory, antioxidant, and neuroprotective properties, has gained attention as a potential treatment for alleviating AD symptoms. In this study, we induced an AD model in female rats through ovariectomy and D-galactose injection and then investigated the protective effects of oral administration of ginger ethanolic extract. We assessed changes in short-chain fatty acids (SCFAs), learning and memory abilities, neuroinflammatory markers in plasma, and the hippocampus, as well as histological changes in the intestine and hippocampus in sham-operated, diseased, and treatment groups. Oral administration of ginger ethanolic extract improved gut microbiota activity, increased SCFA levels, and enhanced the expression of tight junction proteins. Additionally, ginger extract reduced the concentrations of TNF-α and IL-1β in both plasma and the hippocampus. Furthermore, it significantly reduced cell death and amyloid plaque deposition in the hippocampal tissue. These physiological changes resulted in improved performance in learning and memory tasks in rats treated with ginger compared with the disease group. These findings provide compelling evidence for the beneficial effects of ginger on the gut-brain axis, leading to improvements in learning and memory through the reduction of neuroinflammation.

Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy

IntroductionGrowth differentiation factor 15 (GDF15) is a cytokine of the TGFβ family. Here, we analyzed GDF15 levels in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who participated in OCOG-ALMERA (NCT02115464), a phase II randomized clinical trial, that investigated metformin in combination with standard of care concurrent chemoradiotherapy (cCRT). OCOG-ALMERA was not able to demonstrate benefit in the metformin arm. Therefore, biomarker studies are needed to better define stratification parameters for future trials.MethodsPatients were randomized to treatment with platinum-based chemotherapy and concurrent chest radiotherapy (60–66 Gy), with or without metformin (2000 mg/d). The trial collected tumor volume parameters, survival outcomes, and patient blood plasma at baseline, during (weeks 1 and 6) and 6 months after cCRT. Plasma GDF15 levels were assayed with the ELISA method. Statistical analyses explored associations between GDF15, survival outcomes, and radiotherapy tumor volumes.ResultsBaseline plasma levels of GDF15 were elevated in study patients, they increased during cCRT (p < 0.001), and the addition of metformin was associated with a further increase (week 6, p = 0.033). Baseline GDF15 levels correlated with the radiotherapy gross target volume (GTV, p < 0.01), while week 1 of radiotherapy levels correlated with radiotherapy planned target volume (PTV, p < 0.006). In multivariate analysis, baseline plasma GDF15 was prognostic for poor relapse-free (RFS) and overall survival (OS) (p = 0.005 and p = 0.002, respectively).ConclusionsGDF15 is a plasma marker that responds to the treatment of unresected LA-NSCLC with cCRT and metformin. GDF15 levels correspond with tumor volume and increased GDF15 levels predict for poor RFS and OS. These results require validation in larger clinical trial datasets.

Immunology of Schizophrenia: A Modern View on Inflammatory Hypotheses of the Disease

Background: the immunological direction has always been a significant part of biological studies of schizophrenia and in different years has been based on the relevant fundamental ideas about the functions of the immune system and neuroimmune relationships. Objective: to conduct a brief historical analysis of immune hypotheses of schizophrenia, reflecting the vector of research of fundamental immunology, and also to present the results of our own research, confirming the key role of chronic inflammation in the pathogenesis of schizophrenia and the possibility of using immunological indicators for diagnosis and prognosis of the course of the disease. Materials and Method: using the keywords “schizophrenia”, “immune hypotheses of schizophrenia”, “neuroinflammation”, “neuroimmune relationships” we analyzed publications from PubMed/MEDLINE, RSCI databases and other sources of the last decades in comparison with the results of clinical and biological studies of schizophrenia at the Mental Health Research Centre (MHRC). Conclusion: based on the analysis of publications, it is shown that the development of scientfic ideas about the relationship between the immune system and schizophrenia has led to the understanding of the key role of chronic inflammation in the pathogenesis of this disease. Based on comparative studies of a number of immune markers related to cytokine system, acute phase proteins, proteolytic enzymes, etc., a laboratory test system “Neuroimmuno-test”, which includes complex determination of iflammatory and autoimmune markers in blood plasma, was created at the MHRC. It is shown that the level of immune system activation correlates with the features of psychopathological symptoms of patients. Identification of the immune profiles of patients is important to differentiate disease subtypes for the purpose of diagnosis and personalized therapy.

Added value of inflammatory plasma biomarkers to pathologic biomarkers in predicting preclinical Alzheimer's disease.

Plasma biomarkers have recently emerged for the diagnosis, assessment, and disease monitoring of Alzheimer's disease (AD), but have yet to be fully validated in preclinical AD. In addition to AD pathologic plasma biomarkers (amyloid-β (Aβ) and phosphorylated tau (p-tau) species), a proteomic panel can discriminate between symptomatic AD and cognitively unimpaired older adults in a dementia clinic population. Examine the added value of a plasma proteomic panel, validated in symptomatic AD, over standard AD pathologic plasma biomarkers and demographic and genetic (apolipoprotein (APOE) ɛ4 status) risk factors in detecting preclinical AD. 125 cognitively unimpaired older adults (mean age = 66 years) who completed Aβ PET and plasma draw were analyzed using multiple regression with Aβ PET status (positive versus negative) as the outcome to determine the best fit for predicting preclinical AD. Model 1 included age, education, and gender. Model 2 and 3 added predictors APOE ɛ4 status (carrier versus non-carrier) and AD pathologic blood biomarkers (Aβ42/40 ratio, p-tau181), respectively. Random forest modeling established the 5 proteomic markers from the proteomic panel that best predicted Aβ PET status, and these markers were added in Model 4. The best model for predicting Aβ PET status included age, years of education, APOE ɛ4 status, Aβ42/40 ratio, and p-tau181. Adding the top 5 proteomic markers did not significantly improve the model. Proteomic markers in plasma did not add predictive value to standard AD pathologic plasma biomarkers in predicting preclinical AD in this sample.

Identification of Chronic Pancreatitis Associated microRNAs and Genes for the Diagnosis of Pancreatic Cancer.

The timely identification of both malignant and nonmalignant pancreatic lesions has the potential to significantly enhance prognosis and implement risk management strategies across various levels. microRNAs (miRs) and their corresponding targets play a crucial role in the development of pancreatic lesions and can serve as valuable diagnostic and therapeutic targets. The objective of our study was to investigate potential diagnostic markers that can effectively differentiate between malignant and nonmalignant pancreatic lesions. Gene Expression Omnibus (GEO) database with GSE24279 dataset was utilized to screen differentially expressed miRNAs (DEMs). We utilized the TargetScanHuman database to predict the target genes associated with hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p. Furthermore, a cohort comprising healthy individuals (n = 52), chronic pancreatitis (CP; n = 34), and pancreatic adenocarcinoma (PAAD; n = 53) patients was recruited to ascertain the levels of plasma markers. We identified 3 miRNAs (hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p) and 2 proteins (PCDH1 and AMN) as potential diagnostic markers for distinguishing between CP and PAAD. The area under the curve (AUC) values for all markers exceeded .800. Notably, a combination of plasma PCDH1 and AMN demonstrated excellent diagnostic performance (AUC = .921; 95% CI: .866-.977; sensitivity = .792; specificity = .941) in discriminating between CP and PAAD. In addition, the model of hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p yielded an AUC of .928, sensitivity of .830, and specificity of .912, respectively. Plasma levels of miRNAs (hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p) and their corresponding targets (PCDH1 and AMN) hold promise as potential biomarkers for predicting PAAD in patients with CP.

Impact of sample processing delays on plasma markers of inflammation, chemotaxis, cell death, and blood coagulation.

Biosampling studies in critically ill patients traditionally involve bedside collection of samples followed by local processing (ie. centrifugation, aliquotting, and freezing) and storage. However, community hospitals, which care for the majority of Canadian patients, often lack the infrastructure for local processing and storage of specimens. A potential solution is a "simplified" biosampling protocol whereby blood samples are collected at the bedside and then shipped to a central site for processing and storage. One potential limitation of this approach is that delayed processing may alter sample characteristics. To determine whether delays in blood sample processing affect the stability of cytokines (IL-6, TNF, IL-10, IFN-γ), chemokines (IL-8, IP-10, MCP-1, MCP-4, MIP-1α, MIP-1β), cell-free DNA (cfDNA) (released by dying cells), and blood clotting potential in human blood samples. Venous blood was collected into EDTA and citrate sample tubes and stored at room temperature (RT) or 4°C for progressive intervals up to 72 hours, prior to processing. Plasma cytokines and chemokines were quantified using single or multiplex immunoassays. cfDNA was measured using Picogreen DNA Quantification. Blood clotting potential was measured using a thrombin generation assay. Blood samples were collected from 9 intensive care unit (ICU) patients and 7 healthy volunteers. Admission diagnoses for the ICU patients included sepsis, trauma, ruptured abdominal aortic aneurysm, intracranial hemorrhage, gastrointestinal bleed, and hyperkalemia. After pre-processing delays of up to 72 hours at RT or 4°C, no significant changes were observed in plasma cytokines, chemokines, cfDNA, or thrombin formation. Delayed sample processing for up to 72 hours at either RT or 4°C did not significantly affect cytokines, chemokines, cfDNA, or blood clotting potential in plasma samples from healthy volunteers and ICU patients. A "simplified" biosampling protocol is a feasible solution for conducting biosampling research at hospitals without local processing capacity.

Sex differences in the expression of metabolic and pro-inflammatory markers in the initial post-COVID-19 phase

Abstract Cardiovascular complications are a common manifestation of post-acute COVID-19 infection. Post-COVID-19 syndrome is often associated with the female sex and exacerbated inflammation; however, the underlying molecular mechanisms of this sex difference remain poorly understood. In the present study, we aimed to investigate several metabolic, mitochondrial, autophagy, oxidative stress, and inflammatory markers in peripheral blood mononuclear cells (PBMCs) and plasma isolated from older (&amp;gt;75) male and female patients at the initial phase (1-2 weeks) after COVID-19 pneumonia. Age-matched non-infected women and men were used as a control group. We found a significantly higher plasma TNF-α in post-COVID-19 women, but not in men, compared to the control group. Similarly, a significant elevation of IL-1β and IL-18 mRNA in PBMCs from post-COVID-19 women, but not men, was observed. These effects were associated with marked activation of AMPK (defined as pAMPK/AMPK ratio), suggesting potential metabolic stress in female post-COVID-19 PBMCs. Further analysis revealed increased expression of mitochondrial genes, which may be due to AMPK activation as a compensatory reaction to metabolic stress. Analysis of autophagy or oxidative stress (serum 8-OHdG) markers did not reveal any differences between the groups investigated. We conclude that women in the initial phase of post-COVID-19 have elevated expression of inflammatory markers in plasma and in immune cells, which is associated with metabolic stress. This may contribute to the cardiovascular complications in female post-COVID-19 patients.

Epicardial carbohydrate antigen 125 (CA-125) levels, associated with neutrophils activity in heart failure: No differences regarding sex

Abstract Background Carbohydrate antigen 125 (CA125), is the name of the soluble part of mucin-16, after being cleaved, which is detected and increased into circulation in congestive heart failure (HF) patients. Purpose We aimed to study plasma and epicardial fat markers related to inflammation, fibrosis, adiposity, and its association with plasma and epicardial CA125 for understanding the underlying mechanisms of heart failure and the differences between men and women. Methods We have included women and men undergoing open heart surgery (n=134). Epicardial fat biopsy and blood were obtained before the procedure under signed consent. Immunohistochemistry, ELISA, multiplex-Luminex, and real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers. Results Out of 135, 57 patients suffered heart failure (HF). CA125 was expressed on the epicardium. Their levels were positively related to neutrophils, monocytes, and fibroblasts-related markers and negatively to adiposity markers. Both, plasma and epicardial CA125 levels were increased in HF patients. In this group of patients, epicardial CA125 levels were positively associated with circulating and local neutrophil activity, measured by defensin 3 levels. After testing all markers between women and men in HF patients, we observed similar levels in plasma and epicardial CA125. However, higher plasma and epicardial adiposity markers and lower mesothelial marker ITLN-1 were detected in women than in men. Conclusion CA125 is expressed in epicardial cells and its higher levels in HF might explain the higher detected levels in plasma. Its association with local and peripheral neutrophils-related markers with CA125 suggests its common pathophysiological mechanism in women and men. However, high plasma and epicardial adiposity and low mesothelial marker ITNL-1 in epicardium in women might explain the differential mechanism in HF.

Telomere- and oxidative stress dynamics in Psittacidae species with different longevity trajectories.

Telomeres, conserved DNA sequences at chromosome ends, naturally shorten with age, exacerbated by external factors like environmental challenges and reproduction. Birds, particularly psittacine, are gaining prominence as new aging models over the years because of their unique characteristics. This study explores erythrocyte telomere length (TL) and oxidative stress markers in plasma of long- and short-lived captive birds of the order Psittaciformes over four years. Long-lived birds consistently exhibited longer TL than short-lived ones (p = 0.012) but experienced a more pronounced TL shortening rate (p < 0.001) than short-lived ones. Breeding individuals experienced increased TL shortening compared to non-reproductive counterparts in long-lived birds (p = 0.008). Interestingly, long-lived birds showed a higher total antioxidant capacity than short-lived ones (p < 0.001), which was also increased during breeding (p = 0.026). A significant correlation was found between the telomere length shortening rate within the 4years of study and the accumulated oxidative stress (r = 0.426, p = 0.069) in short-lived birds. These findings shed light on TL and oxidative stress dynamics over time, revealing distinct patterns influenced by life-traits among longevity groups.

Metabolomics identifies metabolite markers in plasma and extracellular vesicles within plasma in patients with asthma

BackgroundPlasma and extracellular vesicles (EVs) derived from plasma are important sources of information regarding individual health. Metabolomic analysis of plasma and EVs may provide new methods for predicting disease occurrence. This study aims to analyze the metabolomic characteristics of plasma and plasma EVs in asthma patients. MethodsPlasma samples were collected from healthy individuals and asthma patients. EVs were isolated from the plasma using ultracentrifugation. The isolated EVs were characterized by nanoparticle tracking analysis and flow cytometry. Metabolomic analysis was performed using a liquid chromatography-mass spectrometry platform. ResultsThis study successfully extracted EVs from plasma samples. Metabolomic analysis revealed that the composition of differential metabolites in the plasma and EVs of asthma patients was similar. KEGG pathway analysis indicated that the number of upregulated metabolic pathways enriched with differential metabolites in the plasma EVs of asthma patients was significantly greater than that in the plasma samples. Pathways associated with the onset of asthma included asthma, systemic lupus erythematosus, glycerophospholipid metabolism, and autophagy – other, primarily involving the following five metabolites: PS(18:1(9Z)/18:2(9Z,12Z)), PC(18:1(9Z)e/2:0), PS(24:1(15Z)/22:2(13Z,16Z)), PE(22:4(7Z,10Z,13Z,16Z)/22:5(4Z,7Z,10Z,13Z,16Z)), and PE(16:0/20:3(8Z,11Z,14Z)). Receiver operating characteristic analysis results suggested that these five differential metabolites may serve as potential biomarkers for asthma. ConclusionWe identified the metabolic characteristics of plasma and EVs in asthma patients, confirming that the metabolites in plasma EVs may serve as potential biomarkers for asthma. This finding not only enhances our understanding of the pathogenesis of asthma but also opens new avenues for targeted therapy.

Host Response Markers of Inflammation and Endothelial Activation Associated with COVID-19 Severity and Mortality: A GeoSentinel Prospective Observational Cohort.

The effect of the COVID-19 pandemic on healthcare systems emphasized the need for rapid and effective triage tools to identify patients at risk of severe or fatal infection. Measuring host response markers of inflammation and endothelial activation at clinical presentation may help to inform appropriate triage and care practices in patients with SARS-CoV-2 infection. We enrolled patients with COVID-19 across five GeoSentinel clinical sites (in Italy, Belgium, Canada, and the United States) from September 2020 to December 2021, and analyzed the association of plasma markers, including soluble urokinase-type plasminogen activator receptor (suPAR), soluble tumor necrosis factor receptor-1 (sTREM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), complement component C5a (C5a), von Willebrand factor (VWF-a2), and interleukin-1 receptor antagonist (IL-1Ra), with 28-day (D28) mortality and 7-day (D7) severity (discharged, hospitalized on ward, or died/admitted to the ICU). Of 193 patients, 8.9% (16 of 180) died by D28. Higher concentrations of suPAR were associated with increased odds of mortality at D28 and severity at D7 in univariable and multivariable regression models. The biomarkers sTREM-1 and IL-1Ra showed bivariate associations with mortality at D28 and severity at D7. IL-6, VWF, C5a, and IL-8 were not as indicative of progression to severe disease or death. Conclusions: Our findings confirm previous studies' assertions that point-of-care tests for suPAR and sTREM-1 could facilitate the triage of patients with SARS-CoV-2 infection, which may help guide hospital resource allocation.

Associations between plasma markers and symptoms of anxiety and depression in patients with breast cancer

Background and purposeAmong patients with solid tumors, those with breast cancer (BC) experience the most severe psychological issues, exhibiting a high global prevalence of depression that negatively impacts prognosis. Depression can be easily missed, and clinical markers for its diagnosis are lacking. Therefore, this study in order to investigate the diagnostic markers for BC patients with depression and anxiety and explore the specific changes of metabolism.Method and resultsThirty-eight BC patients and thirty-six matched healthy controls were included in the study. The anxiety and depression symptoms of the participants were evaluated by the 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA). Plasma levels of glial fibrillary acidic protein (GFAP) and lipocalin-2 (LCN2) were evaluated using enzyme linked immunosorbent assay, and plasma lactate levels and metabolic characteristics were analyzed.ConclusionThis study revealed that GFAP and LCN2 may be good diagnostic markers for anxiety or depression in patients with BC and that plasma lactate levels are also a good diagnostic marker for anxiety. In addition, specific changes in metabolism in patients with BC were preliminarily explored.

LPS-induced systemic inflammation is suppressed by the PDZ motif peptide of ZO-1 via regulation of macrophage M1/M2 polarization.

The gram-negative bacterium lipopolysaccharide (LPS) is frequently administered to generate models of systemic inflammation. However, there are several side effects and no effective treatment for LPS-induced systemic inflammation. PEGylated PDZ peptide based on zonula occludens-1 (ZO-1) was analyzed for its effects on systemic inflammation induced by LPS. PDZ peptide administration led to the restoration of tissue injuries (kidney, liver, and lung) and prevented alterations in biochemical plasma markers. The production of pro-inflammatory cytokines was significantly decreased in the plasma and lung BALF in the PDZ-administered mice. Flow cytometry analysis revealed the PDZ peptide significantly inhibited inflammation, mainly by decreasing the population of M1 macrophages, and neutrophils (immature and mature), and increasing M2 macrophages. Using RNA sequencing analysis, the expression levels of the NF-κB-related proteins were lower in PDZ-treated cells than in LPS-treated cells. In addition, wild-type PDZ peptide significantly increased mitochondrial membrane integrity and decreased LPS-induced mitochondria fission. Interestingly, PDZ peptide dramatically could reduce LPS-induced NF-κB signaling, ROS production, and the expression of M1 macrophage marker proteins, but increased the expression of M2 macrophage marker proteins. These results indicated that PEGylated PDZ peptide inhibits LPS-induced systemic inflammation, reducing tissue injuries and reestablishing homeostasis, and may be a therapeutic candidate against systemic inflammation.