Severe COVID-19 Is Characterised by Perturbations in Plasma Amines Correlated with Immune Response Markers, and Linked to Inflammation and Oxidative Stress
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ABSTRACT:
SUBMITTER: Karu N
PROVIDER: S-EPMC9321395 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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| S-EPMC9789945 | biostudies-literature
Project description:ObjectiveTo examine the prospective association between blood biomarkers of immune functioning (i.e., innate immune activation, adaptive immunity, and inflammation) and subsequent cognitive decline and clinical progression to mild cognitive impairment (MCI) in cognitively normal individuals.MethodsThe BIOCARD study is an observational cohort study of N = 191 initially cognitively healthy participants (mean age 65.2 years). Blood plasma samples were assayed for markers of chronic inflammation (TNFR1, IL-6), adaptive immunity (CD25), and innate immune activation (CD14 and CD163). Participants were followed annually for ongoing clinical assessment and cognitive testing for up to 7.3 years. Primary study outcomes were progression to MCI and cognitive change over time, as measured by a global factor score encompassing multiple cognitive domains.ResultsHigher levels of plasma TNFR1 were associated with greater risk of progression from normal cognition to MCI (HR: 3.27; 95% confidence interval, CI: 1.27, 8.40). Elevated levels of TNFR1 were also associated with steeper rate of cognitive decline on follow-up but not with baseline cognitive performance. Baseline IL-6 levels and markers of innate and adaptive immune activation showed no relationship with MCI risk or cognitive decline.ConclusionInflammation, mediated by TNF signaling, may play a selective role in the early phase of AD. Accordingly, plasma TNFR1 may facilitate improved prediction of disease progression for individuals in the preclinical stage of AD.
| S-EPMC6742958 | biostudies-literature
Project description:SARS-CoV-2 infection causes a wide spectrum of disease severity. Identifying the immunological characteristics of severe disease and the risk factors for their development are important in the management of COVID-19. This study aimed to identify and rank clinical and immunological features associated with progression to severe COVID-19 in order to investigate an immunological signature of severe disease. One hundred and eight patients with positive SARS-CoV-2 PCR were recruited. Routine clinical and laboratory markers were measured, as well as myeloid and lymphoid whole-blood immunophenotyping and measurement of the pro-inflammatory cytokines IL-6 and soluble CD25. All analysis was carried out in a routine hospital diagnostic laboratory. Univariate analysis demonstrated that severe disease was most strongly associated with elevated CRP and IL-6, loss of DLA-DR expression on monocytes and CD10 expression on neutrophils. Unbiased machine learning demonstrated that these four features were strongly associated with severe disease, with an average prediction score for severe disease of 0.925. These results demonstrate that these four markers could be used to identify patients developing severe COVID-19 and allow timely delivery of therapeutics.
| S-EPMC8973020 | biostudies-literature
Project description:ObjectiveTo investigate associations of a oxidative balance score (OBS) with blood levels of total cholesterol, low-density lipoprotein- (LDL)-cholesterol, high-density lipoprotein- (HDL) cholesterol and triglycerides, and biomarkers of inflammation (serum C-reactive protein [CRP], albumin and venous total white blood cell [WBC] counts) among 19,825 participants in a nationwide study.MethodsUsing cross-sectional data 14 dietary and lifestyle components were incorporated into the OBS and the resulting score (range 3-26) was then divided into five equal intervals. Multivariable-adjusted odds ratios (ORs) for abnormal biomarker levels and 95% confidence intervals (CIs) were calculated using logistic regression models.ResultsThe ORs (95% CIs) comparing those in the highest relative to those in the lowest OBS equal interval categories were 0.50 (0.38-0.66) for CRP, 0.50 (0.36-0.71) for the total WBC count, and 0.75 (0.58-0.98) for LDL-cholesterol; all three p-values for trend were <0.001. The OBS-HDL-cholesterol association was statistically significantly inverse among females, but not among males. The OBS was not associated with serum albumin or triglycerides.ConclusionOur findings suggest that an OBS may be associated with some, but not all, circulating lipids/lipoproteins and biomarkers of inflammation.
| S-EPMC4609620 | biostudies-literature
Project description:An oxidative balance score (OBS) that combines pro- and antioxidant exposures was previously reported to be associated with incident sporadic colorectal adenoma. We extend the previous analyses by assessing associations of the OBS and colorectal adenoma with circulating biomarkers of oxidative stress [F2-isoprostanes (FIP) and fluorescent oxidation products (FOP)], and inflammation [C-reactive protein (CRP)].Using pooled data from two previously conducted colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 365), the OBS was constructed and divided into three approximately equal intervals, with the lowest interval used as the reference. Biomarker levels were dichotomized as "high" versus "low" based on the median values among controls. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).For the OBS-adenoma association, the ORs (95% CIs) for the middle and highest (relative to the lowest) score intervals were 0.81 (0.46-1.43) and 0.39 (0.17-0.89), respectively. The corresponding OBS category-specific ORs (95% CIs) were 0.50 (0.25-1.01) and 0.25 (0.10-0.65) for FIP, 2.01 (1.13-3.75) and 3.48 (1.51-8.02) for FOP, and 0.57 (0.31-1.04) and 0.21 (0.09-0.49) for CRP. The ORs (95% CIs) reflecting associations of adenoma with high levels of FIP, FOP, and CRP were 1.89 (1.08-3.30), 1.82 (1.11-2.99), and 1.45 (0.88-2.40), respectively.As hypothesized, the OBS was inversely associated with colorectal adenoma and circulating FIP and CRP levels. The reason for the unexpected direct OBS-FOP association is unknown.These data support the use of combined measures of pro- and antioxidant exposures in studies of colorectal neoplasia.
| S-EPMC3959731 | biostudies-literature
Project description:IntroductionHeating tobacco products (HTPs) are advanced electronic cigarette models. Classified by the FDA as a modified-risk tobacco product and can be used as part of efforts to quit smoking. Using heat-not-burn (HnB) technology, these devices heat tobacco avoiding complete combustion. Although the levels of toxicants in the mainstream are significantly lower than those observed in tobacco smoke, some recent studies have raised concerns about potential health risks associated with their use, particularly regarding their effects on male gonadal function, which remain largely unexplored.MethodsAdult male Sprague-Dawley rats were exposed, whole body, 5 days/week for 4 weeks to HnB mainstream.ResultsThe expression of the cell cycle regulators Bax/Bcl-2 ratio is not affected, along with no changes in p-38. On the other hand, an increase in oxidative stress markers, including those associated with DNA damage, was observed in exposed animals, along with the induction of NF-kB dependent pro-inflammatory mediators: TNF-α, IL-1β, IL-6 and COX-2. Furthermore, inactivation of key androgenic enzymes, such as 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, together with decreased testosterone synthesis suggest a potential impairment of male gonadal function.DiscussionThe results indicate that animals exposed to HnB smoke show higher levels of oxidative stress markers, including those associated with DNA damage, as well as higher levels of pro-inflammatory cytokines. The impairment of some androgenic key enzymes and those related to the activity of seminiferous epithelium, together with the decrease in testosterone levels, suggest an impairment of gonadal function through the alteration of some cellular pathways typically associated with tobacco consumption.
| S-EPMC11788375 | biostudies-literature
Project description:BackgroundMetabolic processes form the basis of the development, functioning and maintenance of the brain. Despite accumulating evidence of the vital role of metabolism in brain health, no study to date has comprehensively investigated the link between circulating markers of metabolic activity and in vivo brain morphology in the general population.MethodsWe performed uni- and multivariate regression on metabolomics and MRI data from 24,940 UK Biobank participants, to estimate the individual and combined associations of 249 circulating metabolic markers with 91 measures of global and regional cortical thickness, surface area and subcortical volume. We investigated similarity of the identified spatial patterns with brain maps of neurotransmitters, and used Mendelian randomization to uncover causal relationships between metabolites and the brain.ResultsIntracranial volume and total surface area were highly significantly associated with circulating lipoproteins and glycoprotein acetyls, with correlations up to .15. There were strong regional associations of individual markers with mixed effect directions, with distinct patterns involving frontal and temporal cortical thickness, brainstem and ventricular volume. Mendelian randomization provided evidence of bidirectional causal effects, with the majority of markers affecting frontal and temporal regions.DiscussionThe results indicate strong bidirectional causal relationships between circulating metabolic markers and distinct patterns of global and regional brain morphology. The generated atlas of associations provides a better understanding of the role of metabolic pathways in structural brain development and maintenance, in both health and disease.
| S-EPMC11761619 | biostudies-literature
Project description:Particulate oxidative potential may comprise a key health-relevant parameter of particulate matter (PM) toxicity. To identify biological perturbations associated with particulate oxidative potential and examine the underlying molecular mechanisms, we recruited 54 participants from two dormitories near and far from a congested highway in Atlanta, GA. Fine particulate matter oxidative potential ("FPMOP") levels at the dormitories were measured using dithiothreitol assay. Plasma and saliva samples were collected from participants four times for longitudinal high-resolution metabolic profiling. We conducted metabolome-wide association studies to identify metabolic signals with FPMOP. Leukotriene metabolism and galactose metabolism were top pathways associated with ≥5 FPMOP-related indicators in plasma, while vitamin E metabolism and leukotriene metabolism were found associated with most FPMOP indicators in saliva. We observed different patterns of perturbed pathways significantly associated with water-soluble and -insoluble FPMOPs, respectively. We confirmed five metabolites directly associated with FPMOP, including hypoxanthine, histidine, pyruvate, lactate/glyceraldehyde, and azelaic acid, which were implications of perturbations in acute inflammation, nucleic acid damage and repair, and energy perturbation. The unique metabolic signals were specific to FPMOP, but not PM mass, providing initial indication that FPMOP might constitute a more sensitive, health-relevant measure for elucidating etiologies related to PM2.5 exposures.
| S-EPMC9177558 | biostudies-literature
Project description:Metabolic abnormalities are common in HIV-infected individuals on antiretroviral therapy (ART), but the biochemical details and underlying mechanisms of these disorders have not been defined.Untargeted metabolomic profiling of plasma was performed for 32 HIV patients with low nadir CD4 counts (<300 cells/ul) on protease inhibitor (PI)-based ART and 20 healthy controls using liquid or gas chromatography and mass spectrometry. Effects of Hepatitis C (HCV) co-infection and relationships between altered lipid metabolites and markers of inflammation, microbial translocation, and hepatic function were examined. Unsupervised hierarchical clustering, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), Random forest, pathway mapping, and metabolite set enrichment analysis (MSEA) were performed using dChip, Metaboanalyst, and MSEA software.A 35-metabolite signature mapping to lipid, amino acid, and nucleotide metabolism distinguished HIV patients with advanced disease on PI-based ART from controls regardless of HCV serostatus (p<0.05, false discovery rate (FDR)<0.1). Many altered lipids, including bile acids, sulfated steroids, polyunsaturated fatty acids, and eicosanoids, were ligands of nuclear receptors that regulate metabolism and inflammation. Distinct clusters of altered lipids correlated with markers of inflammation (interferon-? and interleukin-6), microbial translocation (lipopolysaccharide (LPS) and LPS-binding protein), and hepatic function (bilirubin) (p<0.05). Lipid alterations showed substantial overlap with those reported in non-alcoholic fatty liver disease (NALFD). Increased bile acids were associated with noninvasive markers of hepatic fibrosis (FIB-4, APRI, and YKL-40) and correlated with acylcarnitines, a marker of mitochondrial dysfunction.Lipid alterations in HIV patients receiving PI-based ART are linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that therapeutic strategies attenuating dysregulated innate immune activation and hepatic dysfunction may be beneficial for prevention and treatment of metabolic disorders in HIV patients.
| S-EPMC3655873 | biostudies-other
Project description:IntroductionCushing's syndrome (CS) increases cardiovascular risk (CVR) and adipocytokine imbalance, associated with an increased inflammatory state. Telomere length (TL) shortening is a novel CVR marker, associated with inflammation biomarkers. We hypothesized that inflammatory state and higher CVR in CS might be related to TL shortening, as observed in premature aging.AimTo evaluate relationships between TL, CVR and inflammation markers in CS.MethodsIn a cross-sectional study, 77 patients with CS (14 males, 59 pituitary-, 17 adrenal- and 1 ectopic-origin; 21 active disease) and 77 age-, gender-, smoking-matched controls were included. Total white blood cell TL was measured by TRF-Southern technique. Clinical data and blood samples were collected (lipids, adrenal function, glucose). Adiponectin, interleukin-6 (IL6) and C-reactive protein (CRP) were available in a subgroup of patients (n=32). Correlations between TL and clinical features were examined and multiple linear regression analysis was performed to investigate potential predictors of TL.ResultsDyslipidemic CS had shorter TL than non-dyslipidemic subjects (7328±1274 vs 7957±1137 bp, p<0.05). After adjustment for age and body mass index, cured and active CS dyslipidemic patients had shorter TL than non-dyslipidemic CS (cured: 7187±1309 vs 7868±1104; active: 7203±1262 vs 8615±1056, respectively, p<0.05). Total cholesterol and triglycerides negatively correlated with TL (r-0.279 and -0.259, respectively, p<0.05), as well as CRP and IL6 (r-0.412 and -0.441, respectively, p<0.05). No difference in TL according the presence of other individual CVR factors (hypertension, diabetes mellitus, obesity) were observed in CS or in the control group. Additional TL shortening was observed in dyslipidemic obese patients who were also hypertensive, compared to those with two or less CVR factors (6956±1280 vs 7860±1180, respectively, p<0.001). Age and dyslipidemia were independent negative predictors of TL.ConclusionTL is shortened in dyslipidemic CS patients, further worse if hypertension and/or obesity coexist and is negatively correlated with increased inflammation markers. Increased lipids and a "low" grade inflammation may contribute to TL shortening and consequently to premature ageing and increased morbidity in CS.
| S-EPMC4370384 | biostudies-literature