• Journal of Microbiology and Biotechnology
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• v.22 no.5
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• pp.654-658
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• 2012

Osteoarthritis (OA) is the most common rheumatic pathology. One of the major objectives of OA research is the development of early diagnostic strategies such as those using proteomic technology. Synovial fluid (SF) in OA patients is a potential source of biomarkers for OA. The efficient and reliable preparation of SF proteomes is a critical step towards biomarker discovery. In this study, we have optimized a pretreatment method for twodimensional gel electrophoresis (2DE) separation of the SF proteome, by enriching low-abundance proteins and simultaneously removing hyaluronic acid, albumin, and IgG. SF samples pretreated using this optimized method were then evaluated by 1DE and 2DE separation followed by immunodetection of cartilage oligomeric matrix protein (COMP), a known OA biomarker, and by the identification of 3 proteins (apolipoprotein, haptoglobin precursor, and fibrinogen D fragment) that are related to joint diseases.

• Dementia and Neurocognitive Disorders
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• v.23 no.4
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• pp.188-201
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• 2024

Alzheimer's disease (AD), a leading cause of dementia, presents a formidable global health challenge intensified by the aging population. This review encapsulates the evolving landscape of AD diagnosis and treatment with a special focus on the innovative role of fluid biomarkers. Pathologically, AD is marked by amyloid beta (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau, which lead to synaptic dysfunction, neuronal loss, and cognitive decline. These pathological changes, commencing decades before symptom onset, underscore the need for early detection and intervention. Diagnosis traditionally relies on clinical assessment, neuropsychological testing, and neuroimaging techniques. However, fluid biomarkers in cerebrospinal fluid and blood, such as various forms of Aβ, total tau, phosphorylated tau, and neurofilament light chain, are emerging as less invasive, cost-effective diagnostic tools. These biomarkers are pivotal for early diagnosis, differential diagnosis, disease progression monitoring, and treatment response evaluation. The treatment landscape is shifting toward personalized medicine, highlighted by advancements in Aβ immunotherapies, such as lecanemab and donanemab. Demonstrating efficacy in phase III clinical trials, these therapies hold promise as tailored treatment strategies based on individual biomarker profiles. The integration of fluid biomarkers into clinical practice represents a significant advance in AD management, providing the potential for early and precise diagnosis, coupled with personalized therapeutic approaches. This heralds a new era in combating this debilitating disease.

• Journal of Korea Multimedia Society
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• v.23 no.8
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• pp.940-952
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• 2020

The Alzheimer's disease (AD) is a neurodegenerative disease commonly found in the elderly individuals. It is one of the most common forms of dementia; patients with AD suffer from a degradation of cognitive abilities over time. To correctly diagnose AD, compuated-aided system equipped with automatic classification algorithm is of great importance. In this paper, we propose a novel deep learning based classification algorithm that takes advantage of MRI biomarker images including brain areas of hippocampus and cerebrospinal fluid for the purpose of improving the AD classification performance. In particular, we develop a new approach that effectively applies MRI biomarker patch images as input to 3D Deep Convolution Neural Network. To integrate multiple classification results from multiple biomarker patch images, we proposed the effective confidence score fusion that combine classification scores generated from soft-max layer. Experimental results show that AD classification performance can be considerably enhanced by using our proposed approach. Compared to the conventional AD classification approach relying on entire MRI input, our proposed method can improve AD classification performance of up to 10.57% thanks to using biomarker patch images. Moreover, the proposed method can attain better or comparable AD classification performances, compared to state-of-the-art methods.

• Clinical and Experimental Pediatrics
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• v.56 no.1
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• pp.8-12
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• 2013

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

• Tuberculosis and Respiratory Diseases
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• v.67 no.5
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• pp.402-408
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• 2009

Background: Pre-B-cell colony enhancing factor (PBEF) has been suggested as a novel biomarker in sepsis and acute lung injury. We measured the PBEF in bronchoalveolar lavage (BAL) fluid of acute critically ill patients with lung infiltrates in order to evaluate the clinical utility of measuring PBEF in BAL fluid. Methods: BAL fluid was collected by bronchoscope from 185 adult patients with lung infiltrates. An enzyme-linked immunosorbent assay was then performed on the collected fluids to measure the PBEF. Results: Mean patient age was 59.9 ${\pm}$14.5 years and 63.8% of patients were males. The mean concentration of PBEF in BAL fluid was 17.5 ${\pm}$88.3 ng/mL, and patients with more than 9 ng/mL of PBEF concentration (n=26, 14.1%) had higher Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores on the BAL exam day. However, there were no significant differences in clinical characteristics between survivors and non-survivors. In patients with leukocytosis (n=93) seen on the BAL exam day, the linear regression analysis revealed a significant, positive relationship between PBEF and APACHE II ($r^2$=0.06), SOFA score ($r^2$=0.08), Clinical Pulmonary Infection Score ($r^2$=0.05), and plateau pressure in patients on ventilators ($r^2$=0.07) (p<0.05, respectively). In addition, multivariate regression analysis with PBEF as a dependent variable showed that the plateau pressure ($r^2$=0.177, p<0.05) was correlated positively with PBEF. Conclusion: The PBEF level in the BAL fluid may be a useful, new biomarker for predicting the severity of illness and ventilator-induced lung injury in critically ill patients with lung infiltates and leukocytosis.

• Genomics & Informatics
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• v.14 no.1
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• pp.2-11
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• 2016

The advances in mass spectrometry-based proteomics technologies have enabled the generation of global proteome data from tissue or body fluid samples collected from a broad spectrum of human diseases. Comparative proteomic analysis of global proteome data identifies and prioritizes the proteins showing altered abundances, called differentially expressed proteins (DEPs), in disease samples, compared to control samples. Protein biomarker candidates that can serve as indicators of disease states are then selected as key molecules among these proteins. Recently, it has been addressed that cellular pathways can provide better indications of disease states than individual molecules and also network analysis of the DEPs enables effective identification of cellular pathways altered in disease conditions and key molecules representing the altered cellular pathways. Accordingly, a number of network-based approaches to identify disease-related pathways and representative molecules of such pathways have been developed. In this review, we summarize analytical platforms for network-based protein biomarker discovery and key components in the platforms.

• Clinical and Experimental Pediatrics
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• v.65 no.2
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• pp.56-64
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• 2022

Cerebrospinal fluid (CSF) is a dynamic metabolically active body fluid that has many important roles and is commonly analyzed in pediatric patients, mainly to diagnose central nervous system infection and inflammation disorders. CSF components have been extensively evaluated as biomarkers of neurological disorders in adult patients. Circulating microRNAs in CSF are a promising class of biomarkers for various neurological diseases. Due to the complexity of pediatric neurological disorders and difficulty in acquiring CSF samples from pediatric patients, there are challenges in developing CSF biomarkers of pediatric neurological disorders. This review aimed to provide an overview of novel CSF biomarkers of seizure disorders, infection, inflammation, tumor, traumatic brain injuries, intraventricular hemorrhage, and congenital hydrocephalus exclusively observed in pediatric patients.

• Korean Journal of Radiology
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• v.23 no.1
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• pp.89-100
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• 2022

Objective: To improve the N biomarker in the amyloid/tau/neurodegeneration system by radiomics and study its value for predicting cognitive progression in individuals with mild cognitive impairment (MCI). Materials and Methods: A group of 147 healthy controls (HCs) (72 male; mean age ± standard deviation, 73.7 ± 6.3 years), 197 patients with MCI (114 male; 72.2 ± 7.1 years), and 128 patients with Alzheimer's disease (AD) (74 male; 73.7 ± 8.4 years) were included. Optimal A, T, and N biomarkers for discriminating HC and AD were selected using receiver operating characteristic (ROC) curve analysis. A radiomics model containing comprehensive information of the whole cerebral cortex and deep nuclei was established to create a new N biomarker. Cerebrospinal fluid (CSF) biomarkers were evaluated to determine the optimal A or T biomarkers. All MCI patients were followed up until AD conversion or for at least 60 months. The predictive value of A, T, and the radiomics-based N biomarker for cognitive progression of MCI to AD were analyzed using Kaplan-Meier estimates and the log-rank test. Results: The radiomics-based N biomarker showed an ROC curve area of 0.998 for discriminating between AD and HC. CSF Aβ42 and p-tau proteins were identified as the optimal A and T biomarkers, respectively. For MCI patients on the Alzheimer's continuum, isolated A+ was an indicator of cognitive stability, while abnormalities of T and N, separately or simultaneously, indicated a high risk of progression. For MCI patients with suspected non-Alzheimer's disease pathophysiology, isolated T+ indicated cognitive stability, while the appearance of the radiomics-based N+ indicated a high risk of progression to AD. Conclusion: We proposed a new radiomics-based improved N biomarker that could help identify patients with MCI who are at a higher risk for cognitive progression. In addition, we clarified the value of a single A/T/N biomarker for predicting the cognitive progression of MCI.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.447-456
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• 2014

Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) $A{\beta}_{1-42}$, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the clinical utility of CSF biomarkers and the integration of CSF biomarkers in current clinical trials.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.181-187
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• 2009

Intestinal ischemia/reperfusion (I/R) is one of common causes of acute lung injury (ALI). Early and accurate diagnosis of patients who are like to develop serious acute respiratory distress syndrome (ARDS) would give a therapeutic advantage. Ferritin and heme oxygenase-1 (HO-1) are increased by oxidative stress and are potential candidates as a predictive biomarker of ARDS. However, the mechanisms responsible for the increases of ferritin and HO-1, and their relationship to ALI, are unclear. In order to elucidate the interactions between ferritin and HO-1, we studied the changes in ferritin and HO-1 levels in serum and bronchoalveolar lavage (BAL) fluid after intestinal I/R injury in rats. Leukocyte number and protein contents in BAL fluid were elevated following I/R, and the increases were attenuated by mepacrine pretreatment. Both serum ferritin and HO-1 concentrations were progressively elevated throughout the 3 h observation period. Mepacrine pretreatment attenuated the increase of serum and BAL fluid ferritin concentrations, but did not suppress the increase of serum HO-1. Moreover, BAL fluid HO-1 levels did not change after I/R or after mepacrine pretreated I/R compared with sham rats. Unlike ferritin, HO-1 levels are not exactly matched with the ALI. Therefore, there might be a different mechanism between the changes of ferritin and HO-1 in intestinal I/R-induced ALI model.