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Objective: Evaluation of the biomarkers and their relations with sleep in attention deficit hyperactivity disorder (ADHD) is important for understanding the impairments in cognitive functioning. In this study, we aimed to investigate the brain-derived neurotrophic factor (BDNF) and sialic acid (Sia) levels, and their possible relations with chronotypes in ADHD., Methods: The study included 100 drug-naive children with ADHD and 74 healthy children as controls. Conners' Parent Rating Scale-Revised (CPRS-R) scores were used for the severity assessment. Morningness Eveningness Questionnaire (MEQ) was used to determine the chronotypes of participants. ELISA kits were used for the assessment of BDNF and Sia plasma levels., Results: Levels of BDNF and Sia were found to be statistically significantly higher in the ADHD group compared to healthy children (p < 0.001, p < 0.001, respectively). BDNF and Sia levels were found to be higher in the ADHD group with eveningness chronotype (p = 0.045, p = 0.038). The binary logistic regression model was statistically significant (p = 0.033), higher BDNF and Sia levels were assessed as predictive factors for the diagnosis of ADHD. Also, eveningness chronotype was found as a predictive factor of BDNF and Sia levels in ADHD., Conclusion: The results indicate that BDNF and Sia levels, which are related to cognitive functions and sleep, increase with the age of ADHD. Eveningness chronotype, connected with the severity of ADHD, is related to BDNF and Sia levels. There is a need for further studies to confirm these results., (© 2024 International Society for Developmental Neuroscience.)

Host N-glycans play an essential role in the attachment, invasion, and infection processes of viruses, including zoonotic infectious diseases. The similarity of N-glycans in the trachea and lungs of humans and pigs facilitates the cross-species transmission of influenza viruses through respiratory tracts. In this study, the structure and quantity of N-glycans in the plasma of humans, pigs, and chickens were analyzed using liquid chromatography-quadrupole-Orbitrap-tandem mass spectrometry. N-glycans in humans (35), pigs (28), and chickens (53) were identified, including the most abundant, species-common, and species-specific N-glycans. Among the N-glycans (relative quantity >0.5%), the sialic acid derivative of N-acetylneuraminic acid was identified in humans (the sum of the relative quantities of each; 64.3%), pigs (45.5%), and chickens (64.4%), whereas N-glycolylneuraminic acid was only identified in pigs (18.1%). Sialylated N-glycan linkage isomers are the influenza virus receptors (α2-6 in humans, α2-3 and α2-6 in pigs, and α2-3 in chickens). Only α2-6 linkages (human, 58.2%; pig, 44.8%; and chicken, 60.6%) were more abundant than α2-3/α2-6 linkages (human, 4.6%; pig, 0.6%; and chicken, 3.4%) and only α2-3 linkages (human, 1.5%; pig, 0.1%; and chicken, 0.4%). Fucosylation, which can promote viral infection through immune modulation, was more abundant in pigs (76.1%) than in humans (36.4%) and chickens (16.7%). Bisecting N-acetylglucosamine, which can suppress viral infection by inhibiting sialylation, was identified in humans (10.3%) and chickens (16.9%), but not in pigs. These results indicate that plasma N-glycans are similar in humans and chickens. This is the first study to compare plasma N-glycans in humans, pigs, and chickens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The metabolomic profiles of individuals with different clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have not been clearly characterized., Methods: We performed metabolomics analysis of 166 individuals, including 62 healthy controls, 16 individuals with asymptomatic SARS-CoV-2 infection, and 88 patients with moderate (n = 42) and severe (n = 46) symptomatic 2019 coronavirus disease (COVID-19; 17 with short-term and 34 with long-term nucleic-acid test positivity). By examining differential expression, we identified candidate metabolites associated with different SARS-CoV-2 infection presentations. Functional and machine learning analyses were performed to explore the metabolites' functions and verify their candidacy as biomarkers., Results: A total of 417 metabolites were detected. We discovered 70 differentially expressed metabolites that may help differentiate asymptomatic infections from healthy controls and COVID-19 patients with different disease severity. Cyclamic acid and N-Acetylneuraminic Acid were identified to distinguish symptomatic infected patients and asymptomatic infected patients. Shikimic Acid, Glycyrrhetinic acid and 3-Hydroxybutyrate can supply significant insights for distinguishing short-term and long-term nucleic-acid test positivity., Conclusion: Metabolomic profiling may highlight novel biomarkers for the identification of individuals with asymptomatic SARS-CoV-2 infection and further our understanding of the molecular pathogenesis of COVID-19., (© 2024. The Author(s).)

This study investigates the correlation between dietary sialic acid intake which mainly come from eggs, red meat, and dairy products and serum HbA1c levels. A survey among Xiamen's general population, China, collected dietary data from 2,908 participants over the past year. A semi-quantitative food frequency questionnaire (FFQ) was employed. Sialic acid intake was calculated, along with measurements of biochemical indicators, including fasting blood glucose, HbA1c, blood lipids, and insulin. Sociodemographic and physical data were also collected. Logistic regression models evaluated the relationship between dietary sialic acid and HbA1c levels. The daily sialic acid intake in Xiamen's general population was 48.55 (21.68, 65.23) mg/1000Kcal, accompanied by a 1.96% rate of high HbA1c. A significant negative correlation between dietary sialic acid and HbA1c was observed. Individuals in the highest quartile of sialic acid intake (> 65.48 mg/1000 kcal) had a lower risk of high HbA1c compared to those in the lowest quartile (< 23.63 mg/1000 kcal) [OR: 0.123 (0.022, 0.689)]. A high dietary sialic acid intake within a specific range may reduce the risk of elevated HbA1c levels, suggesting a potential preventive effect. Note that this effect is limited to specific intake ranges., (© 2024. The Author(s).)

Objective: To analyze the expression of platelet membrane glycoprotein sialylation in primary immune thrombocytopenia and provide a reference for clinical diagnosis and treatment of the disease., Methods: 100 children with primary immune thrombocytopenia diagnosed and treated in the Children's Hospital of Yunhe District Central Hospital of Cangzhou City, Hebei Province from January 2020 to June 2022 were included in the study group. All children were treated with dexamethasone (DXMS) shock therapy; Another 20 healthy children who underwent routine physical examination at the same time were selected and included in the control group. The study measured the platelet membrane surface in plasma using flow cytometry in two groups: the comparative study group and the control group. The study measured the positive rates of α 2,3-sialic acid (α 2, 3-sa) and α 2,6-sialic acid (α 2, 6-sa) in both groups. The study also measured the positive rates of α 2,3-sialic acid (α 2, 3-sa) and α 2,6-sialic acid (α 2, 6-sa) before and after treatment in the comparative study group. At the same time, an enzyme-linked immunosorbent assay was used to determine the content of sialic acid and sialidase activity and content in the serum. The detection values of α2, 3-SA, and α2, 6-SA expression of children in the study group and the control group were compared, and the detection values of α2, 3-SA, and α2, 6-SA expression of children in the study group before and after treatment were compared., Results: There was no significant difference in the positive rate of α 2, 3-sa between the study group and the control group (t=0.852, P > .05); Study Group: The positive rate of α 2,6-sa was significantly lower than that of the control group (P < .05). In the study group, there was no significant difference in the positive rate of α 2,3-sa before and after treatment (P > .05). However, after treatment, the positive rate of α 2,6-sa was significantly higher than before (P < .05). The study found that the children in the study group had significantly higher levels of serum sialic acid content, sialidase activity, and content than those in the control group (P < .05). After treatment, the children in the study group showed a decrease in serum sialic acid content, sialidase activity, and content, which was statistically significant (P < .05) compared to before treatment., Conclusion: The sialylation of platelet membrane glycoprotein is abnormally expressed in primary immune thrombocytopenia. The sialylation of platelet membrane glycoprotein may be involved in the occurrence and development of the disease. It is of great practical significance to diagnose and evaluate the therapeutic effect of the disease by detecting the sialylation of platelet membrane glycoprotein.

N-Acetyl-D-mannosamine (ManNAc) is an endogenous monosaccharide and precursor of N-acetylneuraminic acid (Neu5Ac), a critical sialic acid. ManNAc is currently under clinical development to treat GNE myopathy, a rare muscle-wasting disease. In this randomized, open-label, 2-sequence, crossover study, 16 healthy women and men were administered a single oral dose of ManNAc under fasting and fed conditions. Blood samples were collected for 48 hours after dosing for quantification of plasma ManNAc and Neu5Ac concentrations. Noncompartmental pharmacokinetic and deconvolution analyses were performed using baseline-corrected plasma concentration data. Administration of ManNAc in the fed state resulted in a 1.6-fold increase in ManNAc exposure, compared to fasting conditions. A concurrent increase in Neu5Ac exposure was observed in the presence of food. Deconvolution analysis indicated that the findings were attributed to prolonged absorption rather than an enhanced rate of absorption. The impact of food on ManNAc pharmacokinetics was greater in women than men (fed/fasted area under the concentration-time curve from time 0 to infinity mean ratio: 198% compared to 121%). It is hypothesized that the presence of food slows gastric emptying, allowing a gradual release of ManNAc into the small intestine, translating into improved ManNAc absorption. The results suggest that taking ManNAc with food may enhance its therapeutic activity and/or reduce the daily dosage requirement., (© 2024 The Author(s). Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: It is known that SARS-CoV-2 mostly infects the respiratory system causing pneumonia; although it can also affect the gastrointestinal tract (GIT), which covered with a bi-layer of mucus rich in glycosylated proteins that terminated by sialic acid. Therefore; this study aimed to evaluate serum total sialic acid (TSA) in moderate COVID-19 patients with and without GIT manifestations., Methods: A total of 161 moderate COVID-19 patients without and with GIT manifestations and 50 controls were enrolled into our study. Serum electrolytes levels were measured by using colorimetric or turbidmetric commercial assay kits, while the level of serum TSA was measured by using a commercial ELISA kit., Results: Our results showed that serum TSA level was highly significantly increased in moderate COVID-19 patients with GIT manifestations (81.43 ± 8.91) when compared with controls (61.24 ± 6.41) or even moderate COVID-19 patients without GIT manifestations (69.46 ± 7.03). ROC curve analysis showed that AUC for TSA is 0.84 with 76.2 % sensitivity and 73.7 % specificity in discrimination between moderate COVID-19 patients with and without GIT manifestations. Serum potassium and sodium levels were highly significantly decreased in moderate COVID-19 patients with GIT manifestations when compared with controls or even moderate COVID-19 patients without GIT manifestations; while serum calcium level was found to be significantly decreased in moderate COVID-19 patients with GIT manifestations when compared with controls., Conclusion: Finally, we can conclude that SA plays a crucial role in the pathogenesis of GIT complications associated with COVID-19 and could be a potential biomarker for the COVID-19 gastrointestinal complications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Cardiac sialylation is involved in a variety of physiological processes in the heart. Altered sialylation has been implicated in heart failure (HF) mice. However, its role in patients with HF is unclear, and the potential effect of modulation of cardiac sialylation is worth exploring., Methods: We first assessed the association between plasma N-acetylneuraminic acid levels and the incidence of adverse cardiovascular events in patients with HF over a median follow-up period of 2 years. Next, immunoblot analysis and lectin histochemistry were performed in cardiac tissue to determine the expression levels of neuraminidases and the extent of cardiac desialylation. Finally, the therapeutic impact of a neuraminidase inhibitor was evaluated in animal models of HF., Results: Among 1699 patients with HF, 464 (27%) died of cardiovascular-related deaths or underwent heart transplantation. We found that the elevated plasma N-acetylneuraminic acid level was independently associated with a higher risk of incident cardiovascular death and heart transplantation (third tertile adjusted hazard ratio, 2.11 [95% CI, 1.67-2.66], P <0.001). In addition, in cardiac tissues from patients with HF, neuraminidase expression was upregulated, accompanied by desialylation. Treatment with oseltamivir, a neuraminidase inhibitor, in HF mice infused with isoproterenol and angiotensin II significantly inhibited desialylation and ameliorated cardiac dysfunction., Conclusions: This study uncovered a significant association between elevated plasma N-acetylneuraminic acid level and an increased risk of a poor clinical outcome in patients with HF. Our data support the notion that desialylation represents an important contributor to the progression of HF, and neuraminidase inhibition may be a potential therapeutic strategy for HF.

In this pilot study, we carried out metabolic profiling of patients with rheumatoid arthritis (RA) starting therapy with biological disease-modifying antirheumatic drugs (bDMARDs). The main aim of the study was to assess the occurring metabolic changes associated with therapy success and metabolic pathways involved. In particular, the potential of the metabolomics profiles was evaluated as therapeutically valuable prognostic indicators of the effectiveness of bDMARD treatment to identify responders versus non-responders prior to implementing treatment. Plasma metabolomic profiles of twenty-five patients with RA prior bDMARD treatment and after three months of therapy were obtained by 1 H NMR, liquid chromatography - mass spectrometry, and gas chromatography - mass spectrometry and evaluated by statistical and multivariate analyses. In the group of responders, significant differences in their metabolic patterns were seen after three months of the bDMARD therapy compared with profiles prior to treatment. We identified 24 metabolites that differed significantly between these two-time points mainly belonging to amino acid metabolism, peptides, lipids, cofactors, and vitamins and xenobiotics. Eleven metabolites differentiated responders versus non-responders before treatment. Additionally, N-acetylglucosamine and N-acetylgalactosamine (GlycA) and N-acetylneuraminic acid (GlycB) persisted significant in comparison responders to non-responders after three months of therapy. Moreover, those two metabolites indicated prediction of response potential by results of receiver-operating characteristic (ROC) curve analysis. The applied analysis provides novel insights into the metabolic pathways involved in RA patient's response to bDMARD and therapy effectiveness. GlycA and GlycB are promising biomarkers to identify responding patients prior onset of bDMARD therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Endometriosis is an inflammatory disease which diagnostics is difficult and often invasive, therefore non-invasive diagnostics methods and parameters are needed for endometriosis detection. The aim of our study was to analyse the glycosylation of native serum IgG and IgG isolated from sera of women classified as: with endometriosis, without endometriosis but with some benign ginecological disease, and control group of healthy women, in context of its utility for differentiation of advanced endometriosis from the group of healthy women. IgG sialylation and galactosylation/agalactosylation degree was determined using specific lectins: MAA and SNA detecting sialic acid α2,3- and α2,6-linked, respectively, RCA-I and GSL-II specific to terminal Gal and terminal GlcNAc, respectively. The results of ROC and cluster analysis showed that the serum IgG MAA-reactivity, sialylation and agalactosylation factor may be used as supplementary parameters for endometriosis diagnostics and could be taken into account as a useful clinical tool to elucidate women with high risk of endometriosis development. Additionally, we have shown that the analysis of native serum IgG glycosylation, without the prior time-consuming and expensive isolation of the protein, is sufficient to differentiation endometriosis from a group of healthy women.

Sialic acid and its associated metabolic enzymes have emerged as important components of the pathophysiology of type 2 diabetes (T2D). There is an elevation in the serum concentration of sialic acid in humans and animals with T2D. The present study investigated the modulation of mRNA expression level of UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) and neuraminidase 1 (NEU1) genes in some organs of type 2 diabetic rats. T2D was induced using fructose-streptozotocin model and eight weeks after the induction of diabetes, sialic acid was assayed in the blood and organs (adipose tissue, brain, colon, kidney, liver, pancreas, skeletal muscle and spleen) followed by quantification of mRNA expression level of GNE and NEU1 genes by qPCR. The results showed a significant (P < 0.05) increase in sialic acid level in the serum and all the afore-mentioned organs investigated except in the adipose tissue and skeletal muscle of the diabetic rats compared the normal control. The expression GNE gene was only increased in the pancreas (1.8-fold) of the diabetic rats while there was a decrease in the expression of the gene in the colon. In contrast, the expression of NEU1 gene was increased in the spleen (3.5-fold), brain (2.2-fold), liver (1.9-fold), colon (1.5-fold) and kidney of the diabetic rats. It was concluded that the elevated level of sialic acid in the organs of diabetic rats, except the pancreas, might not be due to increased endogenous synthesis of sialic acid.

Background: Early diagnosis of sepsis is very important. It is necessary to find effective and adequate biomarkers in order to diagnose sepsis. In this study, we compared the value of sialic acid and procalcitonin for diagnosing sepsis., Methods: Newly admitted intensive care unit patients were enrolled from January 2019 to June 2019. We retrospectively collected patient data, including presence of sepsis or not, procalcitonin level and sialic acid level. Receiver operating characteristic curves for the ability of sialic acid, procalcitonin and combination of sialic acid and procalcitonin to diagnose sepsis were carried out., Results: A total of 644 patients were admitted to our department from January 2019 to June 2019. The incomplete data were found in 147 patients. Finally, 497 patients data were analyzed. The sensitivity, specificity and area under the curve for the diagnosis of sepsis with sialic acid, procalcitonin and combination of sialic acid and procalcitonin were 64.2, 78.3%, 0.763; 67.9, 84.0%, 0.816 and 75.2, 84.6%, 0.854. Moreover, sialic acid had good values for diagnosing septic patients with viral infection, with 87.5% sensitivity, 82.2% specificity, and 0.882 the area under the curve., Conclusions: Compared to procalcitonin, sialic acid had a lower diagnostic efficacy for diagnosing sepsis in critically ill patients. However, the combination of sialic acid and procalcitonin had a higher diagnostic efficacy for sepsis. Moreover, sialic acid had good value for diagnosing virus-induced sepsis.

Background: There is growing evidence that oxidative stress (OS) is a critical factor linking obesity with its associated comorbidities, such as cardiovascular diseases., Aim: To evaluate the degree of OS in people with morbid obesity and its relationship with glycoproteins, determined using 1H-NMR spectroscopy, before and after bariatric surgery (BS)., Methods: In this observational cohort study, plasma from 24 patients with BMI ≥ 40 kg/m 2 (age: 21-65 years) was used to measure metabolites implicated in OS. We measured glycoprotein (GlycA, GlycB and GlycF) areas and shape factors (H/W = height/width)., Results: One year after BS, oxidized low-density lipoprotein had decreased by 49% (P < .0001), malondialdehyde by 32% (P = .0019) and lipoprotein (a) by 21% (P = .0039). The antioxidant enzymes paraoxonase-1 and catalase increased after BS (43%, P < .0001 and 54%, P = .0002, respectively). Superoxide dismutase-2 had fallen 1 year after BS (32%, P = .0052). After BS, both the glycoprotein areas and shape factors decreased by 20%-26%. These glycoproteins were significantly correlated with OS parameters. The plasma atherogenic index was 63% higher in obese individuals than 1 year after BS and correlated positively with glycoproteins., Conclusion: For the first time, we here demonstrate the relationship between OS parameters and glycoproteins in people with morbid obesity. So glycoproteins could therefore be a good indicator, together with the oxidative state to assess patient prognosis after BS., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation Published by John Wiley & Sons Ltd.)

Background: N-acetylneuraminic acid (Neu5Ac) is a functional metabolite involved in coronary artery disease (CAD). We aimed to evaluate the relationship between serum Neu5Ac and the risk and prognosis of acute coronary syndrome (ACS) in a real-world prospective study., Methods: Patients with suspected ACS who underwent coronary angiography were included. Serum Neu5Ac was measured at admission. Coronary lesion severity was evaluated by Gensini Score. GRACE risk stratification was performed at admission. Major adverse cardiac events (MACEs) were recorded during follow-up., Results: A total of 766 patients, including 537 with unstable angina (UAP), 100 with myocardial infarction (MI), and 129 without CAD were included. The circulating Neu5Ac level was significantly higher in patients with MI (median [1QR]: 297[220, 374] ng/ml) than in those with UAP (227 [114, 312] ng/ml) or without CAD (207 [114, 276] ng/ml; both p < 0.001). Serum level of Neu5Ac was positively correlated with age, hypertension, serum uric acid, creatinine, MB isoform of creatine kinase (CK-MB), and Gensini score (all p < 0.05). Receiver operating characteristic curve analysis showed that a higher serum Neu5Ac was potentially associated with MI and high-risk GRACE stratification in ACS patients. Logistic analysis identified only elevated serum Neu5Ac as an independent predictor of MACEs in these patients (odds ratio [OR]: 1.003, 95% confidence interval [CI]: 1.002-1.005, p < 0.001)., Conclusions: Serum Neu5Ac is associated with myocardial injury, GRACE risk category, and prognosis in ACS patients.

Multifactorial mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) might condition the ability of patients with ITP to respond to treatments. Examining their platelet and immune features, we aimed to detect singular characteristics of patients with ITP who do not respond to any treatment. We studied patients with chronic primary ITP who had been without treatment, or untreated (UT-ITP), for at least six months; included were responders to agonists of thrombopoietin receptors (TPO-RA), patients who showed no response to first- and second-line treatments (NR-ITP), and healthy controls. Platelets from NR-ITP patients exposed a reduced amount of sialic acid residues. Increased loss of platelet surface sialic acid residues was associated with increased platelet apoptosis. NR-ITP patients had an increased fraction of naive lymphocyte (L) B cells and a reduced LTreg (Lymphocyte T-regulator) subset. They also presented an anomalous monocyte and NK (Natural Killer) cells distribution. TPO-RA-treated patients seemed to recover an immune homeostasis similar to healthy controls. In conclusion, our results indicate a severe deregulation of the immune system of NR-ITP. The inverse correlation between loss of sialic acid and LTreg count suggests a potential relationship between glycan composition on the platelet surface and immune response, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Objective: Periodontal diseases are inflammatory chronic infections. Sialic acid (SA) is an acute phase reactant by itself. The aim of this study is to investigate the relationship between salivary and serum SA levels and clinical parameters in different forms of periodontal diseases., Subject and Methods: Systemically healthy subjects were included in the study; patients with chronic gingivitis (CG) (n = 10), chronic periodontitis (CP) (n = 10), and aggressive periodontitis (AgP) (n = 10), and ten volunteers with healthy periodontium as the control group. Total SA levels were determined by Warren's thiobarbituric acid method in whole saliva, parotis saliva, and serum samples of subjects before and 3 months after nonsurgical periodontal treatment. Full mouth clinical parameters including plaque index, gingival index, probing depth, and bleeding on probing were also recorded., Results: Before treatment, in both periodontitis groups salivary and serum SA levels were higher than those of controls (P = 0.001). Both salivary and serum SA levels decreased significantly in the patient groups after treatment (P < 0.001). Multiple comparisons of baseline clinical parameters in all groups revealed significant differences (P = 0.001) and these parameters decreased significantly on the 90 th day (P < 0.01). There were positive correlations between SA levels and periodontal indices of the CG, CP, and AgP groups (P < 0.05)., Conclusion: Our results suggest that SA level in both saliva and serum may be a potentially useful marker to determine inflammatory changes and investigate different forms of periodontal diseases., Competing Interests: None

Identifying biomolecules for disease diagnosis requires simple, accurate, and reliable analytical techniques. Multiple signal transduction pathways have promoted the development of various biological analysis systems. However, most systems are largely limited by a single mechanism or model analysis, which can easily lead to false-positive/negative results. Herein, we report a covalent organic framework (COF) ( TpPa-1 ) functionalized with a dye (fluorescein sodium) and design this hybrid material ( TpPa-1@Dye ) to fabricate hydrogels for subsequent analysis with the indicator displacement assay (IDA) method. Selecting a suitable metal cation (Cr 3+ ) for the preparation of hydrogels can reduce the background fluorescence, improve the detection sensitivity, and increase the corresponding sensing selectivity. The TpPa-1@Dye functions as an indicator in the IDA-in-COF system, and Cr 3+ is a receptor of the analyte (sialic acid (SA), a biomarker for ovarian cancer diagnosis). Based on the above studies, the integrative logic operations (AND + IMP) are further established, it helps in elucidating the design rules of the IDA-in-COF approach. This work represents the first effort in designing IDA-in-COF luminescent sensors with an On-Off-On mechanism to determine biomarkers and provides a new approach for developing hybrid COF luminescent materials as analysis platforms for human health monitoring.

Background: Different from the diagnosis of bacterial infections, Mycoplasma pneumoniae pneumonia (MPP) is still lacking of convenient non-specific laboratory parameters., Method: A total of 125 children with MPP were included in the MPP group and 89 children with Mycoplasma-negative pneumonia were included in the control group, and the sera were collected from the children at both the acute and recovery stages in the two groups., Results: The sialic acid and C3 in the MPP group were significantly higher than those in the control group both at the acute and at the recovery stage. On the other hand, the sialic acid and C3 at the acute stage were significantly higher than those at the recovery stage in the MPP group. However, in the control group, the sialic acid and C3 demonstrated IgG exhibited no significant change between the acute stage and the recovery stage. Lastly, positive correlations between sialic acid level and C3 level were identified in the MPP group at both acute and recovery stages., Conclusion: Our study demonstrated that the serum sialic acid correlated with C3 specifically increased in children with MPP, indicating that it might be the important non-specific parameters in the diagnosis of MPP., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Purpose: COPD is a multisystem disease and there is a need for clinical serum markers that can assess the decline in lung and muscle function in COPD. The goal of this study was to evaluate the potential association of serum club-cell protein 16 (CC16), α-1 acid glycoprotein (AGP) and total sialic acid (TSA) with spirometry, hand-grip strength and quality of life to assess important disease outcomes., Methods: This is a population-based cross-sectional study and data were collected from the patients at teaching hospitals of Gomal University and the University of Health Sciences in Pakistan. The study population included 1582 participants (Non-COPD; N = 788, COPD; N = 845) >55 years of age from both sexes, with data from structural interviews, clinical examinations, laboratory investigations, spirometry and hand-grip strength measurements., Results: Serum TSA and CC16 were significant predictors of FEV 1 % (p < 0.05) and hand-grip strength in advanced stages of COPD (p < 0.05 each) in both sexes. Men had higher absolute and adjusted hand-grip strength than women in all groups (p < 0.05). Hand-grip strength was significantly associated with FEV 1 % in both genders (p < 0.05) with stronger effect in women (r 2 = 0.075). Serum HDL-C was an independent predictor of hand-grip strength and FEV 1 % (p < 0.05) in both genders. Participants with extreme problem on EQ-5D parameters had more severe COPD and reduced hand-grip strength (all p values < 0.05)., Conclusion: Taken together, these studies show that the serum expressions of TSA and CC16 have correlations with spirometry and muscle decline in COPD. Further studies should be conducted to establish their efficacy in monitoring disease progression in COPD., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2020 Qaisar et al.)

Aim: The aim of this study was to compare the preoperative and postoperative (48th hour) total serum sialic acid levels of the patients with colon cancer and to investigate if the total serum sialic acid levels can be used as a tumor marker in colon cancer., Methods: Preoperative and postoperative (48th hour) total serum sialic acid levels of 100 patients that were diagnosed with colon cancer and 70 healthy individuals were examined. All total serum sialic acid levels were determined by the methods of Warren., Results: Total sialic acid levels of both patient groups were significantly higher when compared to the control group (p<0.0001). Also, highly significant difference was found between preoperative and postoperative total serum sialic acid levels (p<0.001)., Conclusion: Evaluation of total serum sialic acid levels may play a critical role in colon cancers. Total serum sialic acid levels may serve as a non-invasive tool for early diagnosis of colon cancer., Key Words: Colon cancer, Preoperative, Postoperative, Total sialic acid.

Dengue virus (DENV) causes the most prevalent arboviral infection of humans, resulting in a spectrum of outcomes, ranging from asymptomatic infection to dengue fever to severe dengue characterized by vascular leakage and shock. Previously, we determined that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability, disrupts the endothelial glycocalyx layer (EGL) in vitro and triggers shedding of structural components, including sialic acid (Sia) and heparan sulfate. Here, using a murine model of dengue disease disease, we found high levels of Sia and NS1 circulating in mice with DENV-induced morbidity and lethal DENV infection. Further, we developed a liquid chromatography/mass spectrometry-based method for quantifying free Sia in serum and determined that the levels of free N-glycolylneuraminic acid were significantly higher in DENV-infected mice than in uninfected controls. These data provide additional evidence that DENV infection disrupts EGL components in vivo and warrant further research assessing Sia as a biomarker of severe dengue disease.

The profiles of polytraumatized patients in intensive care units were characterized. Serum and salivary markers were compared with normality between Classes I and II of APACHE II and between periods of hospitalization; these results were correlated. This was a prospective study on saliva charts and collection (n = 70). Profile: male, 27 years old, blunt traumas and collisions. Serum parameters with normality: decrease in pH, creatinine at admission to Class I, and at 48 and 72 hours in both classes; K+ at 48 h in Class II; Ca+ on admission in both classes and at 72 h in Class I. Increase in urea at 72 h in Class II, glucose at all times and in all classes, and Ca+ at 48 h in both classes. Class II had high Na+ at 48 and 72 h compared to Class I. In Class I, creatinine reduction occurred in 48 h and 72 h compared to admission and an increase of Ca+ at 48 h with admission. In Class II, pH and Na+ increased at 48 h and 72 h compared to admission. K+ decreased from admission to 48 h and increased from 48 h to 72 h. Urea increased from 48 to 72 hours. Creatinine decreased from admission to 48 and 72 hours. Ca+ increased from admission to 48 hours and decreased from 48 to 72 hours. There was an increase in the saliva levels in both classes and times in relation to normality. There was an increase in urea at admission, glucose at 72 h, and Ca+ at 48 h in Class II compared with Class I. Class I urea increased from admission to 48 h and Ca+ decreased from admission to 48 h. Class II urea decreased from 48 h to 72 h. Strong or very strong positive correlation was identified between blood and creatinine saliva at all times and regular and negative Ca+ at 72 h. This study provides evidence that salivary and serum biomarkers can be used together to monitor the evolution of the clinical symptoms of ICU patients., Competing Interests: The authors have declared that no competing interests exist.

Caloric restriction mimetics (CRMs) provide an exciting antiaging intervention strategy. 2-Deoxy-D-glucose (2-DG), a glycolytic inhibitor, is known to work as a CRM at high doses; however, at chronic high dose it has been linked to increased mortality in rats. We have investigated chronic low-dose dietary administration of 2-DG on age-related stress protection in young and old male Wistar rats by evaluating age-dependent biomarkers in plasma and erythrocytes. Significant increase was observed in reactive oxygen species levels in 2-DG-treated rats (both young and old), concomitant with increase in activities of erythrocyte plasma membrane redox system (PMRS), catalase (CAT), and superoxide dismutase (SOD). 2-DG treatment also decreased plasma sialic acid and advanced glycation end products. We propose that 2-DG induces a mitohormetic response resulting in augmentation of defense mechanism(s) manifested by higher activity of PMRS, CAT, and SOD. Our findings provide evidence that at chronic low dose 2-DG could be a potential CRM.

A delicate dual-readout immunosensor based on tetraphenylporphyrin-polymer dots (TPP-Pdots) with brilliant photoelectrochemical and photothermal performance was first successfully fabricated for the ultrasensitive detection of sialic acid (SA). Herein, TPP-Pdots with good biocompatibility, extraordinary light-harvesting ability and excellent photothermal conversion efficiency was used to capture SA antibody as dual-functional bioprobe for generating photocurrent and temperature signal. Furthermore, the large surface and morphology-mediated of rutile-TiO 2 (R-TiO 2 ) was beneficial to load amounts of TPP-Pdots for improved PEC signal and photothermal signal. Importantly, the temperature readout resulted from the variation of target concentration could be easily obtained by a universal thermometer which was time-saving and cost-saving. Under the optimized experimental conditions, the photocurrent densities and temperature changes proportionally increased with the increasing of SA concentrations from 3.5 × 10 -5  ng/mL to 35 ng/mL (R = 0.996). Impressively, the dual-readout approach proposed here not only featured with good accuracy and high sensitivity for SA detection, but also paved the way for the development of a dual-readout immunoassay based on PEC biosensor., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Coronary Artery Disease (CAD) has long been recognized as a global health issue. Inflammation, Fibrinolysis and Oxidative Stress play an important role in the disruption of plaques leading to CAD. Markers that reflect this pathophysiologic mechanism may have prognostic value., Objective: To estimate the serum concentrations of high-sensitivity C-reactive protein (hs-CRP), sialic acid (SA), vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), oxidized low density lipoprotein (OX-LDL) and malondialdehyde (MDA) with significant prognostic value in patients with CAD., Methods: The markers included, hs-CRP, SA, VN, PAI-1, OX-LDL and MDA, were compared between 160 angiographically diagnosed CAD patients and 20 age- and sex-matched healthy individuals. The subjects were divided into 4 groups according to angiography results, and association between all risk factors of CAD was studied. Serum levels of SA, VN, PAI-1, and OX-LDL were measured by enzyme-linked immunosorbent assay (ELISA); MDA was measured based on reaction with thiobarbituric acid (TBA); and hs-CRP level was estimated by immunoturbidimetry using a commercial kit. The diagnostic value of these variables was further assessed by ROC curve analysis. Multiple logistic regression was used to evaluate the diagnostic power of the combination. Furthermore, p < 0.05 was considered as significant., Results: Serum levels of hs-CRP, SA, VN, PAI-1, and OX-LDL were significantly higher in patient groups compared to control group (p < 0.001). Using both normal and CAD patients as subjects, ROC analysis was performed. The cutoff for OX-LDL, MDA, PAI-1, VN, hs-CRP and SA was 2.67 (ug/mL), 5.49 (mmol/mL), 67 (ng/mL), 254 (ng/mL), 3.4 (mg/dL), 7/89 (mg/dL), respectively. Eventually, the complete diagnostic efficacy was classified as: SA, hs-CRP, PAI-1, OX-LDL, MDA and VN., Conclusion: Serum levels SA, hs-CRP, VN, PAI-1, OX-LDL and MDA may be predictive of adverse cardiovascular outcomes. Interestingly, these analyses can help as diagnostic and monitoring markers in CAD patients.

Background: Sialic acids are a diverse family of sugar units attached to the outermost ends of sugar chains, which were demonstrated to be related to many diseases. We hypothesized sialic acids could be used as biomarkers for diagnosis of rheumatoid arthritis (RA)., Methods: The serum level of the main sialic acids, N-acetyl-D-neuraminic acid (Neu5Ac) in 163 RA patients and 50 healthy individuals were detected by pre-column derivatization-high performance liquid chromatography method. And three biomarkers to diagnose RA in clinic, C-reactive protein (CRP), rheumatoid factor (RF), and cyclic citrullinated peptides (CCP) in serum of these subjects were analyzed using enzyme-linked immunosorbent assay (ELISA). The data was analyzed using the receiver operating characteristic (ROC) curve and the Youden index., Results: We found the concentration of Neu5Ac in RA group was significantly higher than healthy group. There was a positive correlation between the concentration of Neu5Ac and the RA disease activity score (DAS). The sensitivity and specificity of Neu5Ac were significantly greater than CRP, RF, CCP., Conclusions: Higher serum levels of Neu5Ac were significantly associated with the presence as well as severity of RA. Neu5Ac may be a potential biomarker for prediction and severity of RA in clinical practice., (© 2019 by the Association of Clinical Scientists, Inc.)

Objective: The aim of our study was to evaluate serum high-sensitivity C-Reactive Protein (hs-CRP), sialic acid (SA), and interleukin-6 (IL-6) levels in pregnancies complicated with preeclampsia (PE) and intrauterine growth restriction (IUGR) and to compare with healthy pregnancies., Materials and Methods: This study was conducted at a tertiary-level maternity hospital with 80 pregnant women. Fasting blood samples were taken from 44 consecutive women with pregnancies complicated by PE (n: 20) and IUGR (n: 24), and 36 were from normal pregnancies. Serum hs-CRP, SA, and IL-6 concentrations were measured in all participants., Results: Serum mean hs-CRP, SA, and IL-6 levels were higher in the PE and IUGR group when compared with the control group, but this difference was statistically insignificant (P>0.05). No significant correlation was observed between these inflammatory markers (P>0.05)., Conclusion: The serum levels of hs-CRP, SA, and IL-6 were not elevated in pregnancies complicated with PE and IUGR compared with normal pregnancies. Since pregnancy is already a process with inflammation, fluctuations in some markers related to inflammation may be masked by the gestation itself. A local subclinical inflammation may have a role in the pathogenesis of PE and IUGR rather than systemic inflammation.

Purpose: The purpose of this study was to evaluate the effect of different cardioplegic solutions on endothelial integrity and oxidative stress in cardiovascular surgery., Methods: In this randomized prospective study, after ethics approval and informed consent, 60 surgical patients were included. Patients undergoing coronary bypass surgery were randomized into two groups as warm blood cardioplegia (n = 30) and cold crystalloid cardioplegia (n = 30) following the cross-clamping. Measurements were performed at three time points: before induction of anesthesia (T1), at admission to intensive care unit (ICU) (T2) and at the 24th postoperative hour (T3). Besides biochemical routine hemodynamic monitoring, patients were assessed for the sialic acid (SA), ischemic-modified albumin (IMA), advanced oxide protein products (AOPPs), total thiol (SH), and free hemoglobin (fHb) level., Results: Neither crystalloid nor blood cardioplegia led to significant changes in the AOPPs, T-SH, and SA level (p >0.05). Crystalloid cardioplegia, however, increased IMA level compared to both baseline (p <0.01) and blood cardioplegia group (p <0.05). fHb levels were transiently increased in both groups at the second-time point (p <0.001). fHb level was lower in the crystalloid group compared to that in the other group (p <0.05) at T2., Conclusion: Cardioplegia type creates similar effects on glycocalyx integrity. However, myocardial protection could be provided with warm blood cardioplegia.

Sialic acid is a family of N- and O-substitutions of neuraminic acid. Plasma or serum sialic acid has been established as a potential disease marker. For example, the presence of 9- O-acetyl on the sialic acid of some glycans and glycoconjugates (e.g., 9- O-acetyl GD3 ganglioside) could be related to cancer occurrence. A variety of assays are available to measure serum or plasma sialic acid; however, sample preparation and storage can alter the O-acetylation profile due to the loss of O-acetyl groups and/or the migration of O-acetyl groups. Herein, we report dried blood spot (DBS) sampling, in combination with diamino-4,5-methylenedioxybenzene derivatization, for profiling sialic acids in blood samples with minimal alteration in O-acetylation patterns. The feasibility of the method was first evaluated by analyzing sialic acids in crucian carp blood and comparing with traditional blood/plasma sample preparation procedures. A total of 19 different sialic acids were identified by using liquid chromatography-Orbitrap mass spectrometry, including four mono-O-acetylated N-acetylneuraminic acids, four mono-O-acetylated N-glycolylneuraminic acids, six di-O-acetylated N-acetylneuraminic acids, and three tri-O-acetylated N-acetylneuraminic acids. The long-term storage study indicated that DBS sampling could effectively preserve the O-acetylation information for at least 6 weeks. Thus, it is demonstrated that this method is a valuable tool for the study of sialic acid diversity, especially for the characterization of isomeric structures.

Atherosclerosis is associated with the increased trans-sialidase activity, which can be detected in the blood plasma of atherosclerosis patients. The likely involvement in the disease pathogenesis made this activity an interesting research subject and the enzyme that may perform such activity was isolated and characterized in terms of substrate specificity and enzymatic properties. It was found that the enzyme has distinct optimum pH values, and its activity was enhanced by the presence of Ca2+ ions. Most importantly, the enzyme was able to cause atherogenic modification of lowdensity lipoprotein (LDL) particles in vitro. However, the identity of the discovered enzyme remained to be defined. Currently, sialyltransferases, mainly ST6Gal I, are regarded as major contributors to sialic acid metabolism in human blood. In this mini-review, we discuss the possibility that atherosclerosis- associated trans-sialidase does, in fact, belong to the sialyltransferases family., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sialic acid (SA), a family of acetylated derivatives of neuraminic acid, an acute phase reactant by itself. It usually occurs as a terminal component at the non-reducing end of carbohydrate chains of glycoproteins and glycolipids. SA participates in multiple physiological functions, such as cell-to-cell interactions, cell migration and proliferation. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by rise in blood glucose level. Periodontitis is a chronic inflammatory disease of the periodontal tissue, leading to destruction of bone surrounding the tooth and ultimately tooth loss. There is a two way relationship between diabetes mellitus and periodontitis. Periodontitis is the sixth complication of diabetes along with retinopathy, nephropathy, neuropathy, macrovascular disease, and altered wound healing. Inflammatory mediators like interleukin-6 and tumor necrosis factor-alpha produced during periodontal inflammation can interfere with the actions of insulin receptors and worsen the glycemic control of diabetic patients. Periodontitis is a major cause of tooth loss, affecting over 300 million people and bacteria associated with periodontitis are also linked with systemic problems like endocarditis, atherosclerosis. Recent work has highlighted a major role for the host sugar sialic acid in the biofilm physiology and host-pathogen interactions of T. forsithya, a key periodontal pathogen. There exists a need for a biomarker, for early detection of disease evolution and more robust therapy efficacy measurements. Serum sialic acids were estimated in Indian population by diphenylamine method and Thiobarbituric acid method. The average values were 68 ± 2.6 mg percent by DPA method and 56 ± 5 mg percent by TBA (thiobarbituric acid assay) method. Age and sex showed no influence on serum sialic acid level. Objectives of the present study was to compare (TSSA) level in healthy subjects, subjects with (CMP) with and without (NIDDM) and its effect on non-surgical periodontal therapy. In the present study, the participants were divided into three groups: Group A, B and C. Group A consists of systemically healthy subjects, Group B consists of subjects with (CMP) while Group C consists of subjects with (CMP) with (NIDDM) and results of this study indicated that, at baseline, there were significant differences between Group A, B and Group C with respect to all the clinical parameters, including (GI), (OHI-S), (PPD), (CAL), (TSSA) and (HbA1c) levels. Thus (TSSA) level could be considered as novel biomarker in the progression of periodontal disease and diabetic status. Periodontitis could be considered as a potential, modifiable, and independent risk factor for the development of diabetes. Early detection of elevated (TSSA) level may help in interpreting the progression of periodontitis, risk of development of diabetes mellitus in future and also to prevent complications.

Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans. Sialic acid (SA) generally occurs as the terminal monosaccharide on the glycans. SA in glycoproteins modulates a wide range of physiological and pathological processes and has been routinely measured in hospital since 1950s. Increased serum SA levels have been associated with different types of cancers. However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported. In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed. Based on the mean (SD), median, and p (-Log 10 p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log 10 p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls. Moreover, the greatest increase in the mean (SD) and -Log 10 p values was observed in sepsis and pancreatitis, respectively, but not in cancers. Thus, the regulations of serum SA levels were much more complicated than previously assumed. Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases., (© 2019 Elsevier Inc. All rights reserved.)

Background: The synthesis and glycosylation of glycoproteins and glycolipids take place in the liver. Thus, liver diseases may affect serum concentrations of some carbohydrate derivatives, especially the concentration of sialic acid which is attached to the end of oligosaccharide chains. The aim of this study was to measure and compare the serum concentration of total sialic acid in chronic hepatitis B and C. The hypothesis is that both viruses responsible for the development of inflammation work differently at the cellular level., Methods: Serum samples were obtained from 90 patients suffering from liver diseases: 50 from chronic hepatitis B and 40 from chronic hepatitis C at the time of diagnosis. The total sialic acid concentration in the serum was measured according to the enzymatic method using a colorimetric procedure., Results: The mean total sialic acid concentration in patients with chronic hepatitis B was significantly lower than the mean concentration in the healthy group, while in patients with chronic hepatitis C, it was significantly higher than that in healthy people and in patients suffering from chronic hepatitis B. There were no significant differences in total sialic acid concentrations in patients with chronic hepatitis B and C according to the grade of portal/periportal activity, the grade of lobular activity and the stage of fibrosis., Conclusions: We conclude that chronic viral hepatitis affects the total serum concentration of sialic acid. Moreover, the concentration of total sialic acid may be a useful marker to differentiate between chronic hepatitis B and C but is not useful for evaluation of the progression of these diseases.

Background: In this study, children with phenylketonuria and healthy control subjects were assessed for glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) activity, malondialdehyde (MDA), glutathione (GSH), retinol, cholecalciferol, α-tocopherol, phylloquinone, total sialic acid (TSA), lipid bound sialic acid (LSA), total antioxidant (TAS), total oxidation (TOS), and amino acid levels, and the relationships of these variables with phenylketonuria were evaluated., Methods: The study included 60 children with phenylketonuria and 30 control subjects. Children with phenylketonuria were divided into hyperphenylalaninemia (HPA) and amino acid mixture (AAM) groups., Results: The HPA group had significantly lower levels of GSH-Px, CAT, GSH, TAS, α-aminobutyric acid, and taurine levels (p < 0.01, p < 0.05, p < 0.05, p < 0.001, p < 0.01, p < 0.05, respectively) than the control group. Additionally, the AAM group had significantly lower levels of CAT, TAS, and phylloquinones (p < 0.05, p < 0.05, p < 0.05, respectively) than the control group. It was observed in our study that in the HPA group, a significantly strong positive linear correlation was observed between phenylalanine and α-aminoadipic acid (r = 0.777; p = 0.002)., Conclusions: It was concluded that the levels of α-aminoadipic acid and phylloquinone might be an appropriate choice for the determination of phenylketonuria in parallel with the levels of phenylalanine. α-aminobutyric acid and phylloquinone as a supplement can decrease HPA damage.

The present study aimed to investigate whether sphingosine 1 phosphate (S1P), paraoxonase (PON), total sialic acid (TSA), and heat shock protein-27 (HSP27) are altered in the sheep during infection of the liver with Cysticercus tenuicollis. This study was conducted on40 healthy sheep and40 sheep with Cysticercus tenuicollis infection. The infected and non-infected animals were selected based on the observation of severe Cysticercus tenuicollis infection in the liver and absence of any hepatic cysts, respectively. All parameters were measured in serum and plasma. The results revealed a significant decrease (P&lt;0.01) in PON, TSA, and albumin (Alb) in the infected group, compared with those in the healthy one. Furthermore, the infected sheep had a significant increase (P&lt;0.01) in S1P, HSP-27, malondialdehyde (MDA), total bilirubin, and unconjugated bilirubin as compared with those in their non-infected counterparts. Moreover, no significant change was observed in total plasma protein level in the infected animals in comparison to that in the healthy ones. The low levels of TSA and Alb revealed liver damage in the infected sheep. Moreover, the PON reduction might have resulted from hepatic steatosis and MDA enhancement. Meanwhile, S1P elevation could be attributed to the activation of platelets. In addition, HSP-27 increase was ascribed to the disease-induced stress conditions., (Copyright © 2018, Archives of Razi Institute. Published by Kowsar.)

Circulation of blood depends, in part, on the ability of red blood cells (RBCs) to aggregate, disaggregate, and deform. The primary intrinsic disaggregating force of RBCs is derived from their electronegativity, which is largely determined by sialylated glycoproteins on the plasma membrane. Given supraphysiological shear exposure - even at levels below those which induce hemolysis - alters cell morphology, we hypothesized that exposure to supraphysiological and subhemolytic shear would cleave membrane-bound sialic acid, altering the electrochemical and physical properties of RBCs, and thus increase RBC aggregation. Isolated RBCs from healthy donors (n = 20) were suspended in polyvinylpyrrolidinone. Using a Poiseuille shearing system, RBC suspensions were exposed to 125 Pa for 1.5 s for three duty-cycles. Following the first and third shear duty-cycle, samples were assessed for: RBC aggregation; the ability of RBCs to aggregate independent of plasma ("aggregability"); disaggregation shear rate; membrane-bound sialic acid content, and; cell electrophoretic mobility. Initial shear exposure significantly increased RBC aggregation, aggregability, and the shear required for rouleaux dispersion. Sialic acid concentration significantly decreased on isolated RBC membranes ghosts, and increased in the supernatant following shear. Initial shear exposure decreased the electrophoretic mobility of RBCs, decreasing the electronegative charge from -15.78 ± 0.31 to -7.55 ± 0.21 mV. Three exposures to the shear duty-cycle did not further compound altered RBC measures. A single exposure to supraphysiological and subhemolytic shear significantly decreased the electrochemical charge of the RBC membrane, concurrently increasing cell aggregation/aggregability. The cascading implications of hyperaggregation appears to potentially explain the ischemia-associated complications commonly reported following mechanical circulatory support., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Aim: CDT is a collective biomarker including asialo- and disialo-Tf, but researchers have generally focused attention on disialo-Tf, because of its easier detectability, since asialo-Tf is typically not detectable by the current methods in abstinent individuals, social drinkers and in many alcohol abusers with moderate CDT increases. In the search of a confirmation marker of alcohol-related CDT increases, the detectability of asialo-Tf was re-evaluated comparatively by using CE vs. HPLC., Methods: 468 serum samples compulsorily drawn in a forensic/administrative context were analyzed by CE and HPLC to compare their sensitivity towards asialo-Tf., Results: CE allowed the identification of asialo-Tf in 108 out of 165 CDT "positive" cases, based on disialo-Tf measurement (cut-off 1.8%). HPLC showed a detectable asialo-Tf peak only in 2 cases. In addition, in some cases of disputed CDT increases, the quasi-absence of this Tf component in front of an important increase of disialo-Tf allowed the ruling out of a diagnosis of alcohol abuse, in agreement with all other clinical and laboratory data., Conclusions: The present work shows a superior performance of CE vs. HPLC for the determination of asialo-Tf and the importance of this CDT component to avoid misinterpretation of non-alcohol related CDT increases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The natural ovarian stimulation is mediated by four gonadotrophin glycoforms: FSHtri with three, FSHtetra with four, LHdi with two, and LHtri with three N-glycans. The aim of the study was to determine the serum concentrations of the four glycoforms and their contents of anionic monosaccharides (AMS), i.e. sialic acid (SA) and sulfonated N-acetylgalactosamine (SU) residues throughout the menstrual cycle., Methods: Serum samples were collected from 78 healthy women with regular menstrual cycles. The serum glycoform molecules were identified by their distributions at electrophoreses. Analyses were also performed after removal of terminal SA. The hormones were measured with time-resolved sandwich fluoroimmunoassays., Results: The concentration profiles of the four glycoforms were markedly different. FSHtri, which had a 3-fold higher biopotency than FSHtetra, had peak levels on cycle day 5 and at midcycle and nadirs on cycle days 9 and 21-23. FSHtetra had a raised level on cycle days 5-12, followed by a decrease. LHdi and LHtri had similar patterns, but the peak/nadir ratio was much more pronounced for LHdi than for LHtri, 18 versus 4. The numbers of SA residues per molecule were at a maximum around midcycle when the corresponding numbers of SU were at a minimum. The SU/SA ratio was at a minimum on cycle day 12., Conclusion: The results indicate that the LHdi and the FSHtri molecules play major roles in the natural ovarian stimulation. The SU/SA ratios per molecule favoured a prolonged circulatory half-life of all glycoforms at the midcycle phase. The observations may lead to more successful inductions of ovulation in anovulatory women.

To determine the levels of serum total sialic acid (TSA) in patients with hyperemesis gravidarum (HG) and their gestational age-matched controls. Thirty pregnant women with HG, and 30 healthy pregnant women at up to 14 weeks of gestation were enrolled in this preliminary study. Total sialic acid levels in maternal serum were measured using the quantitative sandwich ELISA method. We observed statistically significant difference in TSA levels between HG and the control groups (p = .003). The identification of the role of SA in the prediction, diagnosis and follow-up of HG warrants more comprehensive studies in the future. Impact Statement What is already known on this subject? The derivatives of neuraminic acid are collectively referred to as sialic acid (SA). Changes in SA levels are known to trigger various conditions and disorders, including inflammatory, cardiovascular, neurological and endocrine diseases. Although a sensitive test capable of identifying hyperemesis gravidarum (HG) would be useful for diagnosis purposes, such a test is currently not available. Studies focussing on identifying new potential indicators and biomarkers for HG - as well as identifying their relevance in establishing diagnosis and assessing disease severity - would not only assist in elucidating the underlying causes of this condition but would also contribute to the development of new diagnostic tests for HG. What the results of this study add? Total sialic acid levels are significantly higher in sera of the patients with HG. The present study is the first in the literature to assess total sialic acid levels in patients with HG and healthy pregnant women before 14 weeks of gestation. What the implications are of these findings for clinical practice and/or further research? Total sialic acid levels could give an idea to clinicians in the etiopathogenesis of HG. The identification of the role of sialic acid in the prediction, diagnosis and follow-up of HG warrants more comprehensive studies in the future.

Objective: Hepatocellular carcinoma is a common primary malignancy of hepatocytes that has caused many fatalities globally. To manage the increasing cases of hepatocellular carcinoma, natural products like mushrooms have been tested for their anti-oxidant, anti-tumour and therapeutic properties. This study aimed to investigate the effect of Agaricus bisporus on progression of chemically induced carcinogenesis in mice. Carcinogenesis was induced in experimental and positive group of mice. Development and progression of carcinogenesis was monitored by quantifying levels of Lactate dehydrogenase, total sialic acid and by histological analysis. The results of the study showed that, unlike lactate dehydrogenase, the levels of sialic acid consistently decreased throughout the experimental period in mice that were fed on mushroom extracts compared to the positive control. Histological analysis also showed protection of the hepatocytes from carcinogenesis progression. Overall, the results from tumour markers and histological analysis, showed that addition of Agaricus bisporus extracts to diet slowed down progression of carcinogenesis and these extracts therefore may be useful as supplementary diet to conventional cancer therapies., (© 2018 Old City Publishing, Inc.)

Background: Raised levels of cholesterol and triglycerides are major risk factors for atherosclerosis, which can lead to coronary heart disease. Both the CRP and Sialic Acid levels are elevated in response to acute as well as chronic inflammatory conditions. This study was conducted to determine the serum lipid profile, CRP and Sialic Acid levels and their relationship with each other in healthy individuals., Methods: This was a cross-sectional study performed by the Department of Biochemistry, Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU) Peshawar. Two hundred healthy subjects in the age group of 18-50 years of either gender was recruited through consecutive sampling. Blood sampling were taken from all the participants and analysed each for serum lipid profile, CRP and Sialic Acid levels through standardized methods., Results: A total of 200 individuals were included, 53.5% being male. Mean age was 33.39±9.76 years. Mean height was 167.86±10.8 cm. Mean weight was 66.87±11.39kg. Mean Hip-Waist ratio was 0.93±0.16 whereas mean BMI was 24.12±3.65. The simultaneous raised levels of serum lipids, CRP and Sialic Acid were observed more commonly in females as compared to males. CRP and Sialic Acid has got statistically significant correlation with HDL. Sialic Acid had statistically significant correlation with triglycerides in the study population with a significant p-value (<0.05), while having a non-significant correlation with total cholesterol and LDL. CRP had got significant correlation with total cholesterol and LDL and non-significant correlation with triglycerides., Conclusions: The study showed that serum CRP and Sialic Acid had a significant negative correlation with serum HDL. A significant positive correlation was found between serum Sialic Acid and triglycerides. CRP and Sialic Acid though expensive but are useful predictors of atherosclerotic disease.

Background: As new biomarkers of coronary artery diseases (CAD) emerge via metabolomics, the underlying functional mechanisms remain to be elucidated. Functional metabolomics aims to translate metabolomics-derived biomarkers to disease mechanisms., Methods: A cohort of 2324 patients who underwent coronary angiography from 4 independent centers was studied. A combination of ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry in the negative ion mode was used for untargeted analysis of metabolites in plasma. Significant differential metabolites were identified by cross-comparisons with and within CAD types, including normal coronary artery, nonobstructvie coronary atherosclerosis, stable angina, unstable angina, and acute myocardial infarction. A tandem liquid chromatography-mass spectrometry-based approach using isotope-labeled standard addition was subsequently performed for targeted analysis of the metabolic marker N -acetylneuraminic acid (Neu5Ac). A functional metabolomics strategy was proposed to investigate the role of Neu5Ac in the progression of CAD by using in vitro and in vivo models., Results: We identified a total of 36 differential metabolites, 35 of which were confirmed with reference compounds. Elevation of Neu5Ac was observed in plasma during CAD progression in center 1 ( P =4.0e-64, n=2019) and replicated in 3 independent centers (n=305). The increased level of Neu5Ac in plasma was confirmed by accurate targeted quantification. Mechanistically, Neu5Ac was able to trigger myocardial injury in vitro and in vivo by activation of the Rho/Rho-associated coiled-coil containing protein kinase signaling pathway through binding to RhoA and Cdc42, but not Rac1. Silencing neuraminidase-1, the enzyme that regulates Neu5Ac generation, ameliorated oxygen-glucose deprivation-induced injury in cardiomyocytes and ligation/isoprenaline-induced myocardial ischemia injury in rats. Pharmacological inhibition of neuraminidase by anti-influenza drugs, oseltamivir and zanamivir, also protected cardiomyocytes and the heart from myocardial injury., Conclusions: Functional metabolomics identified a key role for Neu5Ac in acute myocardial infarction, and targeting neuraminidase-1 may represent an unrecognized therapeutic intervention for CAD., (© 2017 American Heart Association, Inc.)

Erythrocyte membrane is a suitable model to study various metabolic and physiological functions as it undergoes variety of biochemical changes during aging. An age-dependent modulatory effect of rapamycin on erythrocyte membrane functions is completely unknown. Therefore, the present study was undertaken to investigate the effect of rapamycin on age-dependent impaired activities of transporters/exchangers, altered levels of redox biomarkers, viz. protein carbonyl (PC), lipid hydroperoxides (LHs), total thiol (-SH), sialic acid (SA) and intracellular calcium ion [Ca 2+ ]i, and osmotic fragility of erythrocyte membrane. A significant reduction in membrane-bound activities of Na + /K + -ATPase (NKA) and Ca 2+ -ATPase (PMCA), and levels of -SH and SA was observed along with a simultaneous induction in Na + /H + exchanger (NHE) activity and levels of [Ca 2+ ]i, PC, LH and osmotic fragility in old-aged rats. Rapamycin was found to be a promising age-delaying drug that significantly reversed the aging-induced impaired activities of membrane-bound ATPases and altered levels of redox biomarkers.

Introduction: The aim of this study was to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on Paraoxonase (PON1) activity, and levels of lipid profile, total sialic acid (TSA), total antioxidant capacity (TAC) and total oxidant capacity (TOC) in the plasma and brain tissue of mice with chlorpyrifos-ethyl (CPF)-induced Parkinson., Material and Method: In the study, 35 male Swiss albino mice were divided into 5 groups including equal number of mice as follows; intraperitoneal injection of saline for mice in control (C) group, subcutaneous injection of 80mg/kg CPF for CPF group, intraperitoneal injection of 10μmol/kg CAPE for CAPE group, subcutaneous injection of 80mg/kg CPF and intraperitoneal injection of 10μmol/kg CAPE for CPF+CAPE group and intraperitoneal injection of 10% ethanol diluted in physiological saline solution for 21days for ethanol (E) group. All the mice were fed with normal feed and tap water ad libitum. At the end of the study, PON1 activity, lipid profile (except for brain), and TSA, TAC and TOC levels in the plasma and brain tissue were analyzed. Tissue samples of brain substantia nigra were evaluated histopathologically., Results: Levels of plasma TAC, high density lipoprotein (HDL) and PON1 activity were statistically lower in CPF group than the other groups (P<0.001). Also, levels of plasma TOC, TSA, total cholesterol, triglycerides, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were statistically higher in CPF group than the other groups(P<0.001). PON1 activity and level of TAC were significantly lower in brain tissue of CPF groups (P<0.001). In addition, TOC and TSA levels were significantly higher in brain tissue in CPF group (P<0.001)., Conclusion: In conclusion, CAPE showed a protective effect on PON1 activity and levels of lipid profile, TSA, TAC and TOC in plasma and brain tissue and prevented the neurodegenerations in brain tissue in CPF-induced Parkinson's disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Autism spectrum disorders (ASD) may result from a combination of genetic and environmental factors, and impact neurological functions and behaviors. Sialic acid (SA) is an indispensable nutrient for early brain development, and its polymer polySia (PSA) can modify neural cell adhesion molecules (NCAM), thereby indirectly mediating neuronal outgrowth, synaptic connectivity and memory formation. To investigate the association between SA and ASD, we conducted a case-control study., Methods: The study sample included 82 autistic children and 60 healthy children. We measured the levels of plasma SA and serum anti-gangliosides M1 antibodies (anti-GM1 antibodies) in the ASD and control groups. We also examined the severity of autistic children., Results: The level of plasma SA in the control group was significantly higher than that in the ASD group (p < .01). Autistic children had higher positive rates of anti-GM1 antibodies (37.8%) than controls (21.67%, P = .04). However, there was no correlation between autistic severity and the levels of SA. SA may be as a biomarker for diagnosis of ASD with a positive predictive value of 84.42%, a negative predictive value of 73.85% and an area under the ROC curve value of 0.858., Conclusions: These results indicate that SA and anti-GM1 antibodies are associated with ASD. Our data suggested that future studies to explore the function of SA in the etiology of ASD may be needed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

BACKGROUND It is well known that, pathologically, Parkinson's disease is a common neurodegenerative disorder. In Parkinson's disease, the protein which is abundant in the human brain, alpha-synuclein, accumulates inside the nerve cells. In this situation, dysregulation of lipid metabolism performs a crucial role; however, its association with Parkinson's disease is has not yet been explored. MATERIAL AND METHODS We performed a high-performance liquid chromatography-mass spectrometry-derived quantitative lipidomics study to analyze the profile of lipidomic plasma obtained from 170 PD patients and 120 controls, taken from our hospital. A logistic regression model was used for analysis in each of the lipid species having all major classes of glycerolipids, sterols, sphingolipids, and glycerophospholipids. RESULTS We observed that there are differences in the plasma concentrations of 2 lipid subclasses, triacylglycerides and ganglioside-NANA-3, between control and Parkinson's disease participants. The most significant difference between both the participants was observed in the case of ganglioside-NANA-3 plasma concentration (1.293±0.029 pmol/µl versus 1.488±0.041 pmol/µl, respectively) after normalizing it with respect to total lipid. Further, a group of 22 glucosylceramide and ganglioside-NANA-3 species concentration was used for receiver operating characteristic curve analysis after normalizing it with respect to total lipid. The results were quite consistent with previously reported biomarker results. CONCLUSIONS Our results show that there is quite good association between high concentration of ganglioside-NANA-3 species and Parkinson's disease. Interestingly, the same metabolic pathway of glucosylceramide, which is a substrate of the enzyme glucocerebrosidase, has been linked with Parkinson's disease, which is at last followed by ganglioside-NANA-3. These results are supported by earlier works in which lower glucocerebrosidase activity has led to risk of the disease.

GNE myopathy is a rare, autosomal recessive, inborn error of sialic acid metabolism, caused by mutations in GNE, the gene encoding UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase. The disease manifests as an adult-onset myopathy characterized by progressive skeletal muscle weakness and atrophy. There is no medical therapy available for this debilitating disease. Hyposialylation of muscle glycoproteins likely contributes to the pathophysiology of this disease. N-acetyl-D-mannosamine (ManNAc), an uncharged monosaccharide and the first committed precursor in the sialic acid biosynthetic pathway, is a therapeutic candidate that prevents muscle weakness in the mouse model of GNE myopathy. We conducted a first-in-human, randomized, placebo-controlled, double-blind, single-ascending dose study to evaluate safety and pharmacokinetics of ManNAc in GNE myopathy subjects. Single doses of 3 and 6g of oral ManNAc were safe and well tolerated; 10g was associated with diarrhea likely due to unabsorbed ManNAc. Oral ManNAc was absorbed rapidly and exhibited a short half-life (~2.4h). Following administration of a single dose of ManNAc, there was a significant and sustained increase in plasma unconjugated free sialic acid (Neu5Ac) (T max of 8-11h). Neu5Ac levels remained above baseline 48h post-dose in subjects who received a dose of 6 or 10g. Given that Neu5Ac is known to have a short half-life, the prolonged elevation of Neu5Ac after a single dose of ManNAc suggests that intracellular biosynthesis of sialic acid was restored in subjects with GNE myopathy, including those homozygous for mutations in the kinase domain. Simulated plasma concentration-time profiles support a dosing regimen of 6g twice daily for future clinical trials., (Published by Elsevier Inc.)

One hundred each, of Muturu and Bunaji cattle were screened, using polymerase chain reaction (PCR), for trypanosomes in Makurdi and Gboko Local Government Areas of Benue State, Nigeria. Erythrocyte surface sialic acid (ESSA) and free serum sialic acid (FSSA) concentrations were determined and compared in both breeds with the aim of providing baseline data for research and diagnostic purposes. Five per cent (5%) and 23% of the Muturu and Bunaji cattle, respectively, were positive for trypanosomes. The result at p=0.005 was significantly different, with p value of 0.0002 and odd ratio of 0.1762. The Trypanosoma species circulating in Benue State, as detected in the two breeds of cattle, were Trypanosoma congolense, T. vivax, T. brucei and T. evansi. This study, therefore, reports for the first time a natural infection of cattle with T. evansi and the use of a novel PCR in the diagnosis of trypanosome infections in cattle in Benue State, Nigeria. The determination of the ESSA and FSSA concentrations in Muturu cattle in Nigeria is also reported for the first time. The Muturu cattle have a significantly higher ESSA than the Bunaji cattle, this may be responsible for their relative trypanotolerance., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Carcinogenesis is a multistep process where a healthy cell has initially a precancerous stage and finally an early cancerous stage. The process of carcinogenesis can be divided into three stages of initiation, promotion, and progression. In this process, there is increased turnover, secretion, and/or shedding from malignant cells. Glycoproteins like sialic acid are expressed on the cell surface. In oral potentially malignant disorders (OPMDs) and oral cancer (OC), the sialic acid level is seen to increase due to high cell turnover and shedding of malignant cells which, in turn, results in the release of glycoproteins like sialic acid into circulation. Glycoproteins also form an important constituent of salivary mucins and hence due to the same mechanism, an increase in sialic acid level is also seen in saliva., Objective: The aim is to estimate serum and salivary sialic acid levels in healthy controls, patients with OPMDs and patients with OC., Materials and Methods: In this observational cross-sectional study, serum and salivary sialic acid levels were estimated in thirty healthy controls, thirty patients with OPMDs and thirty patients with OC., Results: Serum and salivary sialic acid levels obtained were subjected to statistical analysis. Post hoc Tukey test was used to compare the serum and salivary sialic acid levels of the two study groups to the control group. ANOVA test was used for the comparison of sialic acid levels between the groups. Pearson's correlation coefficient was used to assess correlation (P < 0.05 was considered statistically significant). The mean serum and salivary sialic acid levels were increased significantly in subjects with OPMDs and OC when compared to healthy controls., Conclusion: This study highlights the high expression of sialic acid on outer cell membranes, due to the significant increase in subjects with OPMDs and OC when compared to healthy controls. A significant increase in sialic acid level is also seen in saliva. Hence, it can be stated that saliva can be used as a reliable, noninvasive tool in diagnosis and management of OPMDs and OC.

Background: Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis., Methods: First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 10 9 /L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization., Results: The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4-6) in the oseltamivir group compared with 7 days (interquartile range 5-10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure., Conclusions: Thrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion., Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 .