Biomarkers

Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellula...

Book (in French) published in 2003 at the occasion of the first exhibition staging exclusively biomedia art works at the national art center Le Lieu Unique in Nantes/France. Hauser Jens (ed.): L'Art Biotech. Nantes/Trézélan, 2003.

The publication has not been available anymore since 2008; this PDF is made accessible with the agreement and the kind support of the Filigranes publishing house, until an augmented new edition will be be available. Great thanks to Filigranes and Patrick Le Bescont! https://www.filigranes.com

Dietary advanced glycation end products (AGE) formed during heating of food have gained interest as potential nutritional toxins with adverse effects on inflammation and glucose metabolism. In the present study, we investigated the short-term effects of high and low molecular weight (HMW and LMW) dietary AGE on insulin sensitivity, expression of the receptor for AGE (RAGE), the AGE receptor 1 (AGER1) andTNF-α, F2-isoprostaglandins, body composition and food intake. For 2 weeks, thirty-six Sprague–Dawley rats were fed a diet containing 20 % milk powder with different proportions of this being given as heated milk powder (0, 40 or 100 %), either native (HMW) or hydrolysed (LMW). Gene expression ofRAGEandAGER1in whole blood increased in the group receiving a high AGE LMW diet, which also had the highest urinary excretion of the AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1). Urinary excretion ofNε-carboxymethyl-lysine increased with increasing proportion of heat-treated milk pow...

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).Methods:Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.Results:A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was ident...

Endothelial-derived microparticles (EMPs) are a novel biological marker of endothelium injury and vasomotion disorders that are involved in pathogenesis of cardiovascular, metabolic, and inflammatory diseases. Circulating levels of EMPs are thought to reflect a balance between cell stimulation, proliferation, apoptosis, and cell death. Increased EMPs may be defined in several cardiovascular diseases, such as stable and unstable coronary artery disease, acute and chronic heart failure, hypertension, arrhythmias, thromboembolism, asymptomatic atherosclerosis as well as renal failure, metabolic disorders (including type two diabetes mellitus, abdominal obesity, metabolic syndrome, insulin resistance) and dyslipidemia. This review highlights the controversial opinions regarding impact of circulating EMPs in major cardiovascular and metabolic diseases and summarizes the perspective implementation of the EMPs in risk stratification models.

The present manuscript describes a biomarker capturing strategy based on nanoporous silica particles. The method is shown to enrich the yield of species in the low-molecular weight proteome (LMWP), allowing detection of small peptides in the low-nanomolar range. Plasma samples were exposed to the silica particles, and the captured molecular species were profiled using MALDI-TOF. Mass spectra of the silica-treated human plasma samples showed a significant enrichment in MALDI-TOF protein profiles in the LMWP. Preliminary results indicated good level of reproducibility in plasma profiles with CVs on peak heights ranging from 6.3 to 14.7%. The MALDI-TOF signature changed significantly when the characteristics of the nanoporous silica were altered. The facile sample pretreatment before MS analysis, coupled to the potential for tailoring the surface properties of silica supports, hold promise for improving the recovery of low-abundance serum biomarkers.

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associat...

Stress responses in athletes can be attributed to training and competition, where increased physiological and psychological stress may negatively affect performance and recovery. To examine the relationship between training load (TL) and salivary biomarkers immunoglobulin A (IgA), alpha-amylase (AA), and cortisol across a 16-wk preparation phase and 10-d competition phase in Paralympic swimmers. Four Paralympic swimmers provided biweekly saliva samples during 3 training phases-(1) normal training, (2) intensified training, and (3) taper-as well as daily saliva samples in the 10-d Paralympic competition (2016 Paralympic Games). TL was measured using session rating of perceived exertion. Multilevel analysis identified a significant increase in salivary immunoglobulin A (sIgA: 94.98 [27.69] μg·mL), salivary alpha-amylase (sAA: 45.78 [19.07] μg·mL), and salivary cortisol (7.92 [2.17] nM) during intensified training concurrent with a 38.3% increase in TL. During the taper phase, a 49.5% ...

Information on sCD200 (OX-2), 25-Hydroxyvitamin-D(25(OH)D), homocysteine (hcy), eosinophil cationic peptid (ECP), d-dimer (DD), CXCL8, fractional exhale nitric oxide concentrations (FeNO) status all together among patients with allergy in mediterranean region in comparison of climatic conditions have not been well established yet. Blood samples were taken on May and June during the highest air pollination. Hence, this study was undertaken to compare these serum biomolecules’ levels in allergic patients and matched controls, to evaluate disease characteristics. The study participants (n=129) included 25 healthy individuals (controls) and 104 allergic patients. Consecutive patients with allergic disease (Group II,III,IV,V) above the age of 18 years, managed. In the control group there was a significant positive correlation between ECP and BMI. Positive correlations between ECP, IgE and OX-2 were detected in group IV. For group V patients, positive correlations between age and IgE and ...

Growing evidence suggests that loudness dependency of auditory evoked potentials (LDAEP) and resting EEG alpha and theta may be biological markers for predicting response to antidepressants. In spite of this promise, little is known about the joint reliability of these markers, and thus their clinical applicability. New standardized procedures were developed to improve the compatibility of data acquired with different EEG platforms, and used to examine test-retest reliability for the three electrophysiological measures selected for a multisite project-Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC). Thirty-nine healthy controls across four clinical research sites were tested in two sessions separated by about 1 week. Resting EEG (eyes-open and eyes-closed conditions) was recorded and LDAEP measured using binaural tones (1000 Hz, 40 ms) at five intensities (60-100 dB SPL). Principal components analysis of current source density waveform...

INTRODUCTION Delayed graft function (DGF) is a consequence of ischemia-reperfusion injuries in kidney allografts, for which no definite treatment is available. The neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) are introduced as the most promising urine biomarkers to detect DGF. N-acetylcysteine (NAC) and vitamin C, well-known potent antioxidants that scavenge free radicals, may alleviate kidney injury. This study investigated the protective effects of NAC alone and in combination with vitamin C on DGF, by measuring IL-18 and NGAL in living donor kidney transplantations. MATERIALS AND METHODS Patients transplanted between January 2011 and February 2013 were randomly divided into 3 groups to receive routine anti-rejection medication only (n = 32), NAC plus routine immunosuppressive regimen (NAC group; n = 33), and NAC and vitamin C plus routine regimen (NAC and vitamin C group; n = 19). Urine samples were taken 4 hours and 24 hours after transplantation....

Involuntary weight loss, a part of the cachexia syndrome, is a debilitating co-morbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses, but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anti-cachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK½ inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK is at least in part independent of the tumor. Because single agent MEK inhibitors have been limited as a front-line targeted therapy due to compensatory activation of other o...

Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Knowledge of the cellular and molecular events associated with the formation of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-ᵝ1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has encougaged researchers to continue their research for potent and safer antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans are largely unknown.

The pathophysiology of exocrine dysfunction observed in Sjögren's syndrome (SS) is not fully understood. The purpose of this study was to investigate whether autoan-tibodies against human AQP5 are present in the sera of SS patients. Frozen sections of mouse submandibular salivary glands, CHO cells over-expressing a human AQP5–GFP fusion protein or GFP, and MDCK cells over-expressing AQP5 were used in the indirect immunofluorescence assay to detect anti-AQP5 autoantibodies in the sera from patients with primary SS. The lysates of HEK-293 cells over-expressing the AQP5–GFP fusion protein or GFP were used for immuno-precipitation. Serum IgG from the SS patients but not from the control subjects stained acinar cells in the mouse salivary glands, the signals of which colocalized with those of AQP5-specific antibodies. Serum IgG from the SS patients also selectively stained AQP5–GFP expressed in CHO cells. However, both the control and SS sera immunoprecipitated the AQP5–GFP, suggesting that autoantibodies against AQP5 were also present in the control sera. The screening of 53 control and 112 SS samples by indirect immunofluorescence assay using the AQP5-expressing MDCK cells revealed the presence of significantly higher levels of anti-AQP5 IgG in the SS samples than in the control samples with sensitivity of 0.73 and a specificity of 0.68. Furthermore, the presence of anti-AQP5 autoantibodies was associated with low resting salivary flow in SS patients. In conclusion, anti-AQP5 autoantibodies were detected in the sera from SS patients, which could be a novel biomarker of SS and provide new insight into the pathogenesis of SS.

Approximately 20% of the population has elevated circulating levels of lipoprotein(a) (Lp[a]), one of the most robust predictors of cardiovascular disease risk. This is particularly true for women. Many female patients with "normal" traditional risk factors or low atherosclerotic cardiovascular disease (ASCVD) risk scores may harbor high risk related to elevated levels of Lp(a). A retrospective, cross-sectional study of consecutive female patients presenting to Heart Centers for Women was performed. Discordance between low-density lipoprotein cholesterol (LDL-C) and Lp(a) was determined. The ASCVD risk and Reynolds Risk Score models A (RRS-A) and B (RRS-B) were calculated, and level of agreement in patients meeting treatment threshold (≥7.5% for ASCVD, ≥10% for RRS-A and RRS-B) were compared. Among 713 women, 290 (41%) had elevated Lp(a); however, LDL-C and Lp(a) were weakly correlated (r = 0.08). Significant discordance was observed between abnormal LDL-C and Lp(a) levels...

Recent attention is focused on understanding the genetic basis for individual susceptibility to the development of chronic disease. An emphasis is concentrated on establishing an association be-tween inheritance of polymorphic chemical metab-olizing genes and development of ...

Environmental cadmium contamination is present in some rural villages of Mae Sot District, Tak Province, northwestern Thailand. We compared the health of 751 persons aged ≥ 35 years living in 3 contaminated villages with 682 people from 3 non-contaminated villages with similar socio-demographic and lifestyle characteristics in the same district. All the subjects were screened for urinary cadmium (a biomarker for long-term cadmium exposure), renal function, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, urinary tract stone disease and bone mineral density in 2012. The study renal functions included urinary excretion of β2-microglobulin (early tubular effect), total urine protein and glomerular filtration rate (glomerular effects). The geometric mean of urinary cadmium level was significantly higher among persons living in the contaminated areas (2.96 μg/g creatinine) than those in the non-contaminated areas (0.60 μg/g creatinine). Persons living in contaminated a...

Time spent in moderate-to-vigorous physical activity (MVPA) is a strong predictor of cardiovascular health, yet few humans living in industrialized societies meet current recommendations (150 min/week). Researchers have long suggested that human physiological requirements for aerobic exercise reflect an evolutionary shift to a hunting and gathering foraging strategy, and a recent transition to more sedentary lifestyles likely represents a mismatch with our past in terms of physical activity. The goal of this study is to explore this mismatch by characterizing MVPA and cardiovascular health in the Hadza, a modern hunting and gathering population living in Northern Tanzania. We measured MVPA using continuous heart rate monitoring in 46 participants recruited from two Hadza camps. As part of a larger survey of health in the Hadza, we measured blood pressure (n = 198) and biomarkers of cardiovascular health (n = 23) including C-reactive protein, cholesterol (Total, HDL, and LDL), and tr...

Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. One hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receive...

The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a ...

The occurrence of overweight and obesity has risen around the world. This rate will
increase in the future without appropriate interventions. Obesity is a condition with increased
percentage of fat mass. Evidence based studies indicate that excess adiposity is accompanied
with a proinflammatory state. This low grade chronic inflammation could initiate and progress the metabolic disorders such as insulin resistance, type 2 diabetes, endothelial dysfunction, atherosclerosis and several types of cancers.1
There are outstanding differences between
obesity induced inflammation and classic inflammation. Classic inflammation originates from
the intense immune system response to an insult, results in Basal Metabolic Rate (BMR) increase and usually diminishes over time. In contrast, obesity induced inflammation is chronic,
metabolic, moderate, and is associated with a reduced BMR. Some studies suggested the term
“metaflammation” for this inflammatory condition

Newly discovered cytokines TSLP and IL33 are being studied as important indicators of Th2 inflammation and their effect on Treg cells is likely to modulate immune response. We attempted to study TSLP and IL-33 and then correlated with Tregs in order to find possible biomarker in these patients. Sixty-five children (37 with asthma only and 28 with asthma and rhinitis) aged 6.4 ± 3.2 years (patient group) and 15 healthy children aged 8.0 ± 2.6 years (control group) were recruited in this study. In vitro analysis of TSLP and IL-33 was done in serum samples of 65 newly diagnosed children for allergic asthma and 15 healthy children using the sandwich ELISA method. The expression of Treg cells (CD4 + CD25 + FOXP3+) was analyzed by flow cytometry. The mean TSLP in the patient group (592 ± 68 pg/ml) was significantly higher than controls (215 ± 45 pg/ml) (p < 0.05). Alternatively, the expression of FOXP3 + T reg cells was significantly lower in the patient group (52 ± 36) compared with t...