• 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.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.249-255
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• 2022

Alzheimer's disease (AD) represents a major public health concern and has been identified as a research priority. Clinical research evidence supports that the core cerebrospinal fluid (CSF) biomarkers for AD, including amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau), reflect key elements of AD pathophysiology. Nevertheless, advances in the clinical identification of new indicators will be critical not only for the discovery of sensitive, specific, and reliable biomarkers of preclinical AD pathology, but also for the development of tests that facilitate the early detection and differential diagnosis of dementia and disease progression monitoring. The early detection of AD in its presymptomatic stages would represent a great opportunity for earlier therapeutic intervention. The chance of successful treatment would be increased since interventions would be performed before extensive synaptic damage and neuronal loss would have occurred. In this study, the importance of developing an early diagnostic method using cognitive decline biomarkers that can discriminate between normal, mild cognitive impairment (MCI), and AD preclinical stages has been emphasized.

• Clinical and Experimental Pediatrics
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• v.56 no.7
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• pp.271-274
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• 2013

Brain insults, including neurotrauma, infection, and perinatal injuries such as hypoxic ischemic encephalopathy, generate inflammation in the brain. These inflammatory cascades induce a wide spectrum of cytokines, which can cause neuron degeneration, have neurotoxic effects on brain tissue, and lead to the development of seizures, even if they are subclinical and occur at birth. Cytokines are secreted by the glial cells of the central nervous system and they function as immune system mediators. Cytokines can be proinflammatory or anti-inflammatory. Interleukin (IL)-$1{\beta}$ and IL-8 are proinflammatory cytokines that activate additional cytokine cascades and increase seizure susceptibility and organ damage, whereas IL-1 receptor antagonist and IL-10 act as anti-inflammatory cytokines that have protective and anticonvulsant effects. Therefore, the immune system and its associated inflammatory reactions appear to play an important role in brain damage. Whether cytokine release is relevant for the processes of epileptogenesis and antiepileptogenesis, and whether epileptogenesis could be prevented by immunomodulatory treatment should be addressed in future clinical studies. Furthermore, early detection of brain damage and early intervention are essential for the prevention of disease progression and further neurological complications. Therefore, cytokines might be useful as biomarkers for earlier detection of brain damage in high-risk infants.

• Molecules and Cells
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• v.39 no.8
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• pp.639-644
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• 2016

Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity.

• Parasites, Hosts and Diseases
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• v.48 no.2
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• pp.127-132
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• 2010

Biomphalaria alexandrina snails play an indispensable role in transmission of schistosomiasis. Infection rates in field populations of snails are routinely determined by cercarial shedding neglecting prepatent snail infections, because of lack of a suitable method for diagnosis. The present study aimed at separation and quantification of oxalic, malic, acetic, pyruvic, and fumaric acids using ion-suppression reversed-phase high performance liquid chromatography (HPLC) to test the potentiality of these acids to be used as diagnostic and therapeutic biomarkers. The assay was done in both hemolymph and digestive gland-gonad complex (DGG) samples in a total of 300 B. alexandrina snails. All of the studied acids in both the hemolymph and tissue samples except for the fumaric acid in hemolymph appeared to be good diagnostic biomarkers as they provide not only a good discrimination between the infected snails from the control but also between the studied stages of infection from each other. The most sensitive discriminating acid was malic acid in hemolymph samples as it showed the highest F-ratio. Using the Z-score, malic acid was found to be a good potential therapeutic biomarker in the prepatency stage, oxalic acid and acetic acid in the stage of patency, and malic acid and acetic acid at 2 weeks after patency. Quantification of carboxylic acids, using HPLC strategy, was fast, easy, and accurate in prediction of infected and uninfected snails and possibly to detect the stage of infection. It seems also useful for detection of the most suitable acids to be used as drug targets.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10433-10438
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• 2015

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Aim and Objectives: This study investigated substitutions in the ATP synthase subunit 6 gene of mitochondrial DNA (mtDNA) as a potential diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Based on mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, approximately 465 bp of the ATP synthase subunit 6 gene were amplified and sequenced. Results: The sequencing revealed thirty-one mutations at 14 locations in ATP synthase subunit 6 of mtDNA in the ALL subjects. All were identified as single nucleotide polymorphisms (SNPs) with a homoplasmic pattern. The mutations were distributed between males and females. Novel haplotypes were identified in this investigation: haplotype (G) was recorded in 34% in diagnosed subjects; the second haplotype was (C) with frequency of 13% in ALL subjects. Neither of these were observed in control samples. Conclusions: These haplotypes were identified for the first time in acute lymphoblastic leukemia patients. Five mutations able to change amino acid synthesis for the ATP synthase subunit 6 were associated with acute lymphoblastic leukemia. This investigation could be used to provide an overview of incidence frequency of acute lyphoblastic leukemia (ALL) in Saudi patients based on molecular events.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.113-125
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• 2018

Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

• KIPS Transactions on Software and Data Engineering
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• v.3 no.10
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• pp.421-428
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• 2014

Like Alzheimer's disease, Parkinson's Disease(PD) is one of the most common neurodegenerative brain disorders. PD results from the deterioration of dopaminergic neurons in the brain region called the substantia nigra. Currently there is no cure for PD, but diagnosing in its early stage is important to provide treatments for relieving the symptoms and maintaining quality of life. Unlike many diagnosis methods of PD which use a single biomarker, we developed a diagnosis method that uses both biochemical biomarkers and imaging biomarkers. Our method uses ${\alpha}$-synuclein protein levels in the cerebrospinal fluid and diffusion tensor images(DTI). It achieved an accuracy over 91.3% in the 10-fold cross validation, and the best accuracy of 72% in an independent testing, which suggests a possibility for early detection of PD. We also analyzed the characteristics of the brain fiber pathways of Parkinson's disease patients and normal elderly people.

• Genomics & Informatics
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• v.13 no.3
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• pp.70-75
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• 2015

MicroRNAs (miRNAs) have been demonstrated to play an important role in carcinogenesis. Previous studies revealed that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. In this study, we measured the plasma expression levels of three miRNAs (miR-21, miR-27a, and miR-155) to investigate the usefulness of miRNAs for gastric cancer detection. We initially examined plasma miRNA expression levels in a screening cohort consisting of 15 patients with gastric cancer and 15 healthy controls from Korean population, using TaqMan quantitative real-time polymerase chain reaction. We observed that the expression level of miR-27a was significantly higher in patients with gastric cancer than in healthy controls, whereas the miR-21 and miR-155a expression levels were not significantly higher in the patients with gastric cancer. Therefore, we further validated the miR-27a expression level in 73 paired gastric cancer tissues and in a validation plasma cohort from 35 patients with gastric cancer and 35 healthy controls. In both the gastric cancer tissues and the validation plasma cohort, the miR-27a expression levels were significantly higher in patients with gastric cancer. Receiver-operator characteristic (ROC) analysis of the validation cohort, revealed an area under the ROC curve value of 0.70 with 75% sensitivity and 56% specificity in discriminating gastric cancer. Thus, the miR-27a expression level in plasma could be a useful biomarker for the diagnosis and/or prognosis of gastric cancer.

• Journal of Korean Medical Science
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• v.33 no.53
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• pp.342.1-342.6
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• 2018

We validated the diagnostic performance of a previously developed blood-based 7-protein biomarker panel, $AptoDetect^{TM}$-Lung (Aptamer Sciences Inc., Pohang, Korea) using modified aptamer-based proteomic technology for lung cancer detection. Non-small cell lung cancer (NSCLC), 200 patients and benign nodule controls, 200 participants were enrolled. In a high-risk population corresponding to ${\geq}55years$ of age and ${\geq}30pack-years$, the diagnostic performance was improved, showing 73.3% sensitivity and 90.5% specificity with an area under the curve of 0.88. $AptoDetect^{TM}$-Lung (Aptamer Sciences Inc.) offers the best validated performance to discriminate NSCLC from benign nodule controls in a high-risk population and could play a complementary role in lung cancer screening.