scholarly journals Mass Spectrometry-Based Identification of New Serum Biomarkers in Patients with Latent Infection Pulmonary Tuberculosis

2021 ◽  
Author(s):  
Yan-Xia Li ◽  
Kang-Di Zheng ◽  
Yu Duan ◽  
Hua-Juan Liu ◽  
Yu-Qun Tang ◽  
...  
Keyword(s):  
Disease Progression ◽  
Latent Infection ◽  
Disease Diagnosis ◽  
Serum Biomarkers ◽  
Nucleotide Metabolism ◽  
Functional Enrichment ◽  
Disease Assessment ◽  
Serum Samples ◽  
Change Analysis ◽  
Metabolic Markers

Abstract Background: To screen specific metabolic markers serum metabolic biomarkers which can achieve the main monitoring indicators to evaluate the development from latent infection to active tuberculosis infection, and analysis its underlying mechanisms and functions. Methods: Four groups of serum, including healthy control, latent infection, drug sensitivity (DS), and drug resistant tuberculosis, were collected. The metabolites in all serum samples were extracted by oscillatory, deproteinization, and then were detected by LC-MS/MS analysis. Normalization by Pareto-scaling method, the difference analysis was carried out by Metaboanalyst 4.0 software, one-way ANOVA analysis among groups showed that p-value ≤0.05 was regarded as a different metabolite. To clarify the dynamic changes and functions of differential metabolites with disease progression, and explore its significance and mechanism as a marker by further cluster analysis, functional enrichment analysis, and relative content change analysis of differential metabolites. Results: There were 565 significantly different metabolites in four groups. Differential metabolites, including Indole-3-acetaldehyde, Theophylline, Inosine and Prostaglandin H2, etc., may be the key serum biomarkers to diagnose the period of latent infection of Mycobacterium tuberculosis (M. tuberculosis). which was closely related to Amino acid metabolism, Biosynthesis of other secondary metabolites, Nucleotide metabolism, Endocrine system, Immune system, Lipid metabolism, and Nervous system. Conclusion: Indole-3-acetaldehyde, Theophylline, Inosine, and Prostaglandin H2, the 4 metabolites may be potential markers diagnosing the period of latent infection of M. tuberculosis. Meanwhile, Inosine and Prostaglandin E1 can become potential biomarkers for the diagnosis of latent infection, and Theophylline and Cotinine 1 can be used as potential markers to monitor disease progression, which established strategy provided promising clinical application prospects for the development of disease assessment by combining small molecule metabolic markers to improve the sensitivity and specificity of disease diagnosis.

scholarly journals Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rowan AlEjielat ◽  
Anas Khaleel ◽  
Amneh H. Tarkhan
Keyword(s):  
Gene Expression ◽  
Ankylosing Spondylitis ◽  
Differentially Expressed Genes ◽  
Gene Network ◽  
Disease Diagnosis ◽  
Receptor Activation ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Inflammatory Disorder ◽  
Data Set

Abstract Background Ankylosing spondylitis (AS) is a rare inflammatory disorder affecting the spinal joints. Although we know some of the genetic factors that are associated with the disease, the molecular basis of this illness has not yet been fully elucidated, and the genes involved in AS pathogenesis have not been entirely identified. The current study aimed at constructing a gene network that may serve as an AS gene signature and biomarker, both of which will help in disease diagnosis and the identification of therapeutic targets. Previously published gene expression profiles of 16 AS patients and 16 gender- and age-matched controls that were profiled on the Illumina HumanHT-12 V3.0 Expression BeadChip platform were mined. Patients were Portuguese, 21 to 64 years old, were diagnosed based on the modified New York criteria, and had Bath Ankylosing Spondylitis Disease Activity Index scores > 4 and Bath Ankylosing Spondylitis Functional Index scores > 4. All patients were receiving only NSAIDs and/or sulphasalazine. Functional enrichment and pathway analysis were performed to create an interaction network of differentially expressed genes. Results ITM2A, ICOS, VSIG10L, CD59, TRAC, and CTLA-4 were among the significantly differentially expressed genes in AS, but the most significantly downregulated genes were the HLA-DRB6, HLA-DRB5, HLA-DRB4, HLA-DRB3, HLA-DRB1, HLA-DQB1, ITM2A, and CTLA-4 genes. The genes in this study were mostly associated with the regulation of the immune system processes, parts of cell membrane, and signaling related to T cell receptor and antigen receptor, in addition to some overlaps related to the IL2 STAT signaling, as well as the androgen response. The most significantly over-represented pathways in the data set were associated with the “RUNX1 and FOXP3 which control the development of regulatory T lymphocytes (Tregs)” and the “GABA receptor activation” pathways. Conclusions Comprehensive gene analysis of differentially expressed genes in AS reveals a significant gene network that is involved in a multitude of important immune and inflammatory pathways. These pathways and networks might serve as biomarkers for AS and can potentially help in diagnosing the disease and identifying future targets for treatment.

scholarly journals Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soo Hyun Cho ◽  
Sookyoung Woo ◽  
Changsoo Kim ◽  
Hee Jin Kim ◽  
Hyemin Jang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Assessment ◽  
Time Interval ◽  
Disease Course ◽  
Preclinical Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
Preclinical Ad ◽  
Cognitive Subscale

AbstractTo characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

scholarly journals Natural history and disease progression of early cardiac amyloidosis evaluated by echocardiography

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
O Itzhaki Ben Zadok ◽  
A Eisen ◽  
Y Shapira ◽  
D Monakier ◽  
Z Iakobishvili ◽  
...  
Keyword(s):  
Disease Progression ◽  
Wall Thickness ◽  
Cardiac Amyloidosis ◽  
Time Course ◽  
Right Ventricular Dysfunction ◽  
Disease Diagnosis ◽  
Left Ventricular ◽  
Funding Sources ◽  
Lv Mass ◽  
Echocardiographic Findings

Abstract Funding Acknowledgements Type of funding sources: None. Background Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of already advanced cardiomyopathy. Aims to describe early echocardiographic features in patients subsequently diagnosed with CA and to delineate disease progression. Methods Pre-amyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic amyloid subtype (immunoglobulin light-chain (AL) or amyloid transthyretin (ATTR)). Abnormalities were defined based on published guidelines. Results Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 (IQR 1.0, 1.5)cm) ≥3 years before the diagnosis of CA and relative wall thickness (RWT) was increased (0.47 (IQR 0.41, 0.50)) ≥7 years pre-diagnosis. Between 1 to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction (LVEF)≤50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased RWT (0.74 (IQR 0.62, 0.92) vs. 0.62 (IQR 0.54, 0.76), p = 0.004) and LV mass index (144 (IQR 129, 191) vs. 115 (IQR 105, 146)g/m2,p = 0.020) and reduced LVEF (50 (IQR 44, 58) vs. (60 (IQR 53, 60)%, p = 0.009) throughout the time course of CA progression, albeit survival time was similar. Conclusions Increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography Abstract Figure. Schematic proposed timeline of CA

scholarly journals Methodology and Applications of Disease Biomarker Identification in Human Serum

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Ziad J. Sahab ◽  
Suzan M. Semaan ◽  
Qing-Xiang Amy Sang
Keyword(s):  
Human Serum ◽  
Protein Separation ◽  
High Sensitivity ◽  
Disease Diagnosis ◽  
Plasma Lipoproteins ◽  
Great Promise ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Disease Biomarkers ◽  
Diagnosis And Prognosis

Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.

scholarly journals Dynamic Analysis of Serum MMP-7 and Its Relationship with Disease Progression in Biliary Atresia: A Multicenter Prospective Study

2021 ◽  
Author(s):  
Shuiqing Chi ◽  
Peipei Xu ◽  
Pu Yu ◽  
Guoqing Cao ◽  
Haibin Wang ◽  
...  
Keyword(s):  
Prospective Study ◽  
Biliary Atresia ◽  
Disease Progression ◽  
Genetic Mutation ◽  
Mediation Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Concentration ◽  
Clinical Value ◽  
Serum Samples ◽  
Matrix Metalloproteinase 7

Abstract PurposeWe aimed to assess the dynamic changing trend of serum matrix metalloproteinase-7 (MMP-7) in BA patients from diagnosis to LTx to further elucidate its clinical value in diagnosis and prognoses and its relationship with disease progression.MethodsIn this multicentre prospective study, a total of 440 cholestasis patients (direct bilirubin level of > 17 μmol/L) were enrolled. Serum and stool MMP-7 levels were measured using an enzyme-linked immunosorbent assay at different time points and analysed. The polymorphism of MMP-7 was assessed to explore the possible reasons for the low value in BA patients.Results:In neonate biliary atresia patients, using a cut-off value of > 26.73 ng/ml, serum MMP-7 had a AUC of 0.954. A genetic mutation (G137D) and rapid degradation of MMP-7 in serum samples could cause low MMP-7 levels in serum of BA patients. Four dynamic patterns of serum MMP-7 post-KPE were associated with prognosis. A high concentration of MMP-7 in the stool is linked to a decreased serum MMP-7 concentration. MMP-7 showed a mediation effect on the association between inflammation and liver fibrosis in BA patients. Serum MMP-7 was the only significant predictor at six weeks post-KPE and the most accurate predictor at three months post-KPE of survival with the native liver (SNL) in two years.Conclusion:As one of the critical factors associated with BA occurrence and progression, serum MMP-7 can be used for early diagnosis of BA and post-KPE MMP-7 level is the earliest prognostic biomarker so far.

scholarly journals Influence of publication year, add-on design, and geographical region on the progression of Alzheimer’s disease: a modeling analysis of literature aggregate data

2020 ◽  
Author(s):  
ningyuan zhang ◽  
Xijun Zheng ◽  
Hongxia Liu ◽  
Qingshan Zheng ◽  
Lujin Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Assessment ◽  
Progression Rate ◽  
Progression Model ◽  
Geographical Regions ◽  
Significant Difference ◽  
Disease Progression Rate ◽  
Disease Progression Model

Abstract Background Our objective was to develop a disease progression model for cognitive decline in Alzheimer’s disease (AD) and to determine whether disease progression of AD is related to the year of publication, add-on trial design, and geographical regions. Methods Placebo-controlled randomized AD clinical trials were systemically searched in public databases. Longitudinal placebo response (mean change from baseline in the cognitive subscale of the Alzheimer’s Disease Assessment Scale [ADAS-cog]) and the corresponding demographic information were extracted to establish a disease progression model. Covariate screening and subgroup analyses were performed to identify potential factors affecting the disease progression rate. Results A total of 142 publications (148 trials) were included in this model-based meta-analysis. The typical disease progression rate was 5.82 points per year. The baseline ADAS-cog score was included in the final model using an inverse-U type function. Age was found to be negatively correlated with disease progression rate. After correcting the baseline ADAS-cog score and the age effect, no significant difference in disease progression rate was found between trials published before and after 2008, and between trials using add-on design and those that did not use add-on design. However, a significant difference was found among different trial regions. Trials in East Asian countries showed the slowest decline rate and the largest placebo effect. Conclusions Our model successfully quantified AD disease progression by integrating baseline ADAS-cog score and age as important predictors. These factors and geographic location should be considered when optimizing future trial designs and conducting indirect comparisons of clinical outcomes.

scholarly journals Evaluation of Multiplexed Fluorescent Microsphere Immunoassay for Detection of Autoantibodies to Nuclear Antigens

2004 ◽  
Vol 11 (6) ◽  
pp. 1054-1059 ◽  
Author(s):  
Thomas B. Martins ◽  
Rufus Burlingame ◽  
Carlos A. von Mühlen ◽  
Troy D. Jaskowski ◽  
Christine M. Litwin ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Vascular Diseases ◽  
Disease Diagnosis ◽  
Specific Method ◽  
Serum Samples ◽  
Collagen Vascular Diseases ◽  
Fluorescent Microsphere ◽  
Nuclear Antigens ◽  
Multiplexed Fluorescent Microsphere Immunoassay ◽  
Microsphere Immunoassay

ABSTRACT Antibodies to extractable nuclear antigens (ENA) are found in a variety of collagen vascular diseases. Determining the individual specificities of these antibodies is extremely useful in establishing the disease diagnosis and in some cases the prognosis. With a multiplexed fluorescent microsphere immunoassay, reactivity to five of the most diagnostically useful ENA was measured in 249 serum samples, including samples from 56 patients previously documented to have systemic lupus erythematosus (SLE). Results of the multiplexed assay were compared to results from established ENA enzyme-linked immunosorbent assays (ELISAs), and the agreement, sensitivity, and specificity, respectively, for the five ENA evaluated were as follows: SSA, 99.1, 100.0, and 98.8%; SSB, 98.6, 88.9, and 99.5%; Sm, 97.6, 95.8, and 97.9%; RNP, 97.2, 92.7, and 98.8%; Scl-70, 93.6, 50.0, and 99.0%. In the 56 confirmed SLE patients, the frequency of significant concentrations of autoantibodies with the multiplexed assay was 21.4% for SSA, 7.1% for SSB, 10.7% for Sm, 32.1% for RNP, and 0% for Scl-70. The new flow cytometric bead-based multiplexed assay showed excellent correlation with the well-established single-analyte ELISA methods for four of five the ENA markers investigated in this study. The most notable discrepancies between the two assays were for the Scl-70 antigen, which was most often resolved in favor of the multiplexed assay. Our studies show that the multiplexed microsphere-based immunoassay is a sensitive and specific method for the detection and semiquantitation of ENA antibodies in human sera.

Abstract P426: Association of Serum Soy Isoflavones with Metabolic Markers in Japanese Men and Women

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Rhobert W Evans ◽  
Akira Sekikawa ◽  
Takashi Kadowaki ◽  
Abhishek Vishnu ◽  
Sayaka Kadowaki ◽  
...  
Keyword(s):  
Correlation Coefficients ◽  
Population Based ◽  
Japanese Women ◽  
Soy Isoflavones ◽  
Serum Samples ◽  
Japanese Men ◽  
Metabolic Markers ◽  
Men And Women ◽  
Isoflavone Concentration ◽  
Very High

Objectives: Soy isoflavones may have beneficial roles as antioxidants and phytoestrogens. Dietary intake varies widely across populations: very high in Japan but low in North America. We measured the concentrations of daidzein and genistein in the serum of Japanese men and women and evaluated their associations with metabolic markers. Methods: Serum samples were obtained from a population based sample of 94 Japanese men (mean age 45.3), and 142 Japanese women (mean age 66.6; 97% were post-menopausal). Isoflavones were analyzed after extraction and derivatization using GC-MS. Concentrations of daidzein and genistein were summed to obtain total isoflavone concentrations. Results: Isoflavone concentrations were very high among the Japanese. Median values (nM) for men: 558, 452 and 86 and for women 660, 494 and 150 (total isoflavones, genistein and daidzein, respectively). Spearman correlation coefficients for the isoflavones with multiple outcomes among Japanese men and women are shown in the table. No significant (p<0.05) associations were observed among the men but borderline negative associations were observed for total isoflavones (p=0.063) and genistein (p=0.063) with LDLc. Among women there was a significant association between total isoflavones (p=0.041) and daidzein (p=0.006) with HDLc. Borderline significant associations were also observed for total isoflavones (p=0.068) and genistein (p=0.061) with glucose. Discussion: The concentrations of isoflavones are high in the Japanese, approximately 50 times greater than those of N. Americans. Associations between the isoflavones and various outcomes were very weak for the Japanese men. This possibly reflects a plateau of isoflavone concentration has been reached that precludes observing any associations. Although, many correlations were calculated the positive associations of total isoflavones and daidzein with HDLc among women may be real. HDLc concentrations are high in Japanese women which may reflect the estrogenic actions of isoflavones.

scholarly journals Metabolic signature of obesity-associated insulin resistance and type 2 diabetes

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Haya Al-Sulaiti ◽  
Ilhame Diboun ◽  
Maha V. Agha ◽  
Fatima F. S. Mohamed ◽  
Stephen Atkin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Serum Samples ◽  
Metabolic Markers ◽  
Insulin Resistant ◽  
Increased Risk ◽  
Novel Biomarkers ◽  
Prospective Cohorts

Abstract Background Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

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