• Korean Journal of Biological Psychiatry
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• v.30 no.1
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• pp.24-30
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• 2023

Objectives Alzheimer's disease (AD) is the most common form of dementia in older adults, damaging the brain and resulting in impaired memory, thinking, and behavior. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. The aim of our study was to identify differentially expressed genes associated with AD and combined biomarkers among them to improve AD risk prediction accuracy. Methods Machine learning methods were used to compare the performance of the identified combined biomarkers. In this study, three publicly available gene expression datasets from the hippocampal brain region were used. Results We detected 31 significant common genes from two different microarray datasets using the limma package. Some of them belonged to 11 biological pathways. Combined biomarkers were identified in two microarray datasets and were evaluated in a different dataset. The performance of the predictive models using the combined biomarkers was superior to those of models using a single gene. When two genes were combined, the most predictive gene set in the evaluation dataset was ATR and PRKCB when linear discriminant analysis was applied. Conclusions Combined biomarkers showed good performance in predicting the risk of AD. The constructed predictive nomogram using combined biomarkers could easily be used by clinicians to identify high-risk individuals so that more efficient trials could be designed to reduce the incidence of AD.

• Korean Journal of Environmental Biology
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• v.42 no.1
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• pp.1-14
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• 2024

This study evaluated the risk of single and combined exposure to microplastics in zebrafish (Danio rerio) through biomarkers, such as survival rate, excretion rate, and histological alterations of organ systems. The experimental groups were the control(Cont.), single microplastics exposure group(MPs, 1.83%/fish total weight(g)), the copper group(Cu, 21.6 ㎍ L^-1), and a group with combined exposure to MPs and copper (MPs^*Cu). The experiment was conducted with individual exposure (7 days) for MP excretion rate analysis and group exposure (14 days) for biomarker analysis. The daily excretion rate of MPs tended to decrease in a time-dependent manner. The copper concentration in the body was not significantly different between single and combined copper exposure. The degeneration of mucous cells in the skin, capillary dilation of the gill lamella, increased intestinal mucous, hepatocyte hypertrophy, and the degeneration of glomeruli and renal tubules were observed in all exposure groups. These histological alterations showed the highest tendency in the MPs^*Cu group. In this study, the changes in biomarkers were attributed to the single effect of copper or the combined effect of copper and MPs rather than being solely influenced by MPs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1911-1915
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• 2012

Aim: New technologies for the early detection of pancreatic cancer (PC) are urgently needed. The aim of the present study was to screen for the potential protein biomarkers in serum using proteomic fingerprint technology. Methods: Magnetic beads combined with surface-enhanced laser desorption/ionization (SELDI) TOF MS were used to profile and compare the protein spectra of serum samples from 85 patients with pancreatic cancer, 50 patients with acute-on-chronic pancreatitis and 98 healthy blood donors. Proteomic patterns associated with pancreatic cancer were identified with Biomarker Patterns Software. Results: A total of 37 differential m/z peaks were identified that were related to PC (P < 0.01). A tree model of biomarkers was constructed with the software based on the three biomarkers (7762 Da, 8560 Da, 11654 Da), this showing excellent separation between pancreatic cancer and non-cancer., with a sensitivity of 93.3% and a specificity of 95.6%. Blind test data showed a sensitivity of 88% and a specificity of 91.4%. Conclusions: The results suggested that serum biomarkers for pancreatic cancer can be detected using SELDI-TOF-MS combined with magnetic beads. Application of combined biomarkers may provide a powerful and reliable diagnostic method for pancreatic cancer with a high sensitivity and specificity.

• Tuberculosis and Respiratory Diseases
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• v.83 no.3
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• pp.185-194
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• 2020

Blood eosinophil counts have emerged as a chronic obstructive pulmonary disease (COPD) biomarker that predict the effects of inhaled corticosteroids (ICS) in clinical practice. Post-hoc and prospective analysis of randomized control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to ICS. COPD patients with frequent exacerbations (2 or more moderate exacerbations/yr) or a history of hospitalization have a greater response to ICS. Ex-smokers also appear to have a greater ICS response. Blood eosinophil counts can be combined with clinical information such as exacerbation history and smoking status to enable a precision medicine approach to the use of ICS. Higher blood eosinophil counts are associated with increased eosinophilic lung inflammation, and other biological features that may contribute to the increased ICS response observed. Emerging data indicates that lower blood eosinophil counts are associated with an increased risk of bacterial infection, suggesting complex relationships between eosinophils, ICS response, and the airway microbiome.

• KSBB Journal
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• v.26 no.4
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• pp.352-356
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• 2011

The detection of biomarkers is an important issue for disease diagnosis. However, many systems are not suitable to detect the biomarker itself directly. For direct detection of biomarker proteins in human serum, a new affinity-capture method using aptamers combined with the mass spectrometry was suggested. Since signals from protein samples cannot be amplified, modified chromatin immunoprecipitation (ChIP) and subsequent cross-linking with formaldehyde between aptamers and target proteins were used not to lose the captured target proteins, which allowed us to perform a harsh washing step to remove the non-specifically bound proteins. As a model system, a thrombin aptamer was used as a bait and thrombin as a target protein. Using our modified ChIP and affinity-capture method, non-specific binding proteins on the beads decreased significantly, suggesting that our new method is efficient and can be applied to developing diagnosis systems for various biomarkers.

• BMB Reports
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• v.41 no.9
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• pp.626-634
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• 2008

Novel cancer biomarkers are required to achieve early diagnosis and optimized therapy for individual patients. Cancer is a disease of the genome, and tumor tissues are a rich source of cancer biomarkers as they contain the functional translation of the genome, namely the proteome. Investigation of the tumor tissue proteome allows the identification of proteomic signatures corresponding to clinico-pathological parameters, and individual proteins in such signatures will be good biomarker candidates. Tumor tissues are also a rich source for plasma biomarkers, because proteins released from tumor tissues may be more cancer specific than those from non-tumor cells. Two-dimensional difference gel electrophoresis (2D-DIGE) with novel ultra high sensitive fluorescent dyes (CyDye DIGE Fluor satulation dye) enables the efficient protein expression profiling of laser-microdissected tissue samples. The combined use of laser microdissection allows accurate proteomic profiling of specific cells in tumor tissues. To develop clinical applications using the identified biomarkers, collaboration between research scientists, clinicians and diagnostic companies is essential, particularly in the early phases of the biomarker development projects. The proteomics modalities currently available have the potential to lead to the development of clinical applications, and channeling the wealth of produced information towards concrete and specific clinical purposes is urgent.

• Mass Spectrometry Letters
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• v.1 no.1
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• pp.21-24
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• 2010

The development of clinical biomarkers involves discovery, verification, and validation. Recently, multiple reaction monitoring (MRM) coupled with stable isotope dilution mass spectrometry (IDMS) has shown considerable promise for the direct quantification of proteins in clinical samples. In particular, multiple biomarkers have been tracked in a single experiment using MRM-based MS approaches combined with liquid chromatography. We report here a highly reproducible, quantitative, and dynamic MRM system for validating multi-biomarker proteins using Nanoflow HPLC-Microfluidics Chip/Triple-Quadrupole MS. In this system, transitions were acquired only during the retention window of each eluting peptide. Transitions with the highest MRM-MS intensities for the five target peptides from colon cancer biomarker candidates were automatically selected using Optimizer software. Relative to the corresponding non-dynamic system, the dynamic MRM provided significantly improved coefficients of variation in experiments with large numbers of transitions. Linear responses were obtained with concentrations ranging from fmol to pmol for five target peptides.

• Applied Chemistry for Engineering
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• v.33 no.5
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• pp.451-458
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• 2022

Semiconductor quantum dots (QDs) are optical probes with excellent fluorescence properties. Therefore, they have been applied to various bio-medical imaging techniques and biosensors. Due to the unique optical characteristics of wide absorption and narrow fluorescence energy bands, multiple types of signals can be generated by the combination of fluorescence wavelengths from different QDs, which enables the simultaneous detection of more than two biomarkers. In this review, the advantages and applications of QDs and QD nanobeads (QBs) in multiple biomarker assays were described, and new developments or improvements in multiplexed biomarker detection techniques were summarized. In particular, recent reports were summarized, focusing on the design strategies in immunoassay construction and signal transducing materials for fluorescence-linked immunosorbent assays using QDs and immunochromatographic assays using QBs. New detection platforms will be developed for early diagnosis of diseases and other fields if multiplexed detection technologies of excellent accuracy and sensitivity are combined with artificial intelligence algorithms.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.122-136
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• 2022

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents and surgical approaches may be beneficial in patients with CPFE, but further studies are needed.

• Journal of Veterinary Clinics
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• v.40 no.6
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• pp.399-407
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• 2023

Chronic kidney disease (CKD) occurs in more than 15% of the dogs over 10 years of age and causes irreversible renal function deterioration. Therefore, it is important to diagnose CKD early and treat the disease properly. The purpose of this study aimed to to evaluate the clinical utility of urine albumin/creatinine ratio (ACR) using POC (point-of-care) device as an early detection urinary biomarker in CKD dogs and to confirm the correlation between ACR and other known CKD biomarkers. Urine and serum samples were obtained from 50 healthy dogs and 50 dogs with CKD. Serum blood urea nitrogen (BUN), creatinine, and symmetric dimethylarginine (SDMA) concentrations, and urine protein creatinine ratio (UPC) were measured. Urine specific gravity (USG) was evaluated using refractometer, and ACR was measured using an i-SENS A1Care analyzer. The ACR values of dogs with CKD were significantly different from those of healthy dogs (p < 0.001), as with other renal biomarkers. ACR showed significant differences between healthy dogs and dogs with CKD at every IRIS stage (p < 0.005), whereas no significant differences were observed between dogs with CKD IRIS stage I and healthy dogs with UPC. There are significant positive correlation between ACR and BUN (r = 0.611, p < 0.001), creatinine (r = 0.788, p < 0.001), SDMA (r = 0.747, p < 0.001), and UPC (r = 0.784, p < 0.001), and significant negative correlation between ACR and USG (r = -0.700, p < 0.001). In receiver operator characteristic curve analysis, the area under the curve (AUC) was 0.982 (95% CI 0.963-1.000, p < 0.001), with an optimal cut-off value of 64.20 mg/g (94% sensitivity and 94% specificity). Thus, ACR is a useful urinary biomarker for the early diagnosis of proteinuria in CKD and combined use of ACR and other renal biomarkers may be helpful for early diagnosis and prevention of CKD in dogs.