• 대한의생명과학회지
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• 제3권2호
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• pp.151-160
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• 1997

본 연구는 카드뮴의 이용 및 환경 오염의 증가로 일어날 수 있는 카드뮴 중독에 대한 새로운 생물학적 지표로서의 요중 ascorbic acid를 평가하기 위하여 실험적으로 중독시킨 Sprague-Dawley종의 흰쥐를 이용하여 요중 ascorbic acid측정, 신장의 조직병리학적 조사 및 생화학적 간 기능 검사를 실시하였다. 측정 된 요중 ascorbic acid 농도의 전 실험기간 (50일) 평균치는 실험군I (카드뮴 100 ppm)이 214.0 mg/dl, 실험군II (카드뮴 200 ppm)가 254.3 mg/dl로 대조군 9.0 mg/dl에 비해 각각 24배 및 28배의 증가를 보였다. 조직병리학적 소견으로는 신장의 근위 세뇨관에서 단백뇨의 원인으로 추정되는 호산성 초자양 물질이 관찰되어 신장의 손상이 있었고, 생화학적 분석에서 실험군I에서 AST, ALT의 수치가 대조군의 143 mg/dl, 50 mg/dl에 비해 각각 199 mg/dl, 88 mg/dl, 실험군II가 270 mg/dl, 226 mg/dl로 나타나 간 기능의 손상이 있었음을 알 수 있었다. 이상의 결과로 실험동물이 카드뮴에 노출됨에 따라 그 아만성 독성으로서 간장 및 신장 기능의 손상이 있었고 또한 요중의 ascorbic acid가 현저하게 증가되어 요중 ascorbic acid가 실험 동물의 카드뮴 노출에 대한 noninvasive 진단 지표로서 활용될 수 있을 것으로 기대된다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제27권4호
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• pp.236-245
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• 2024

Purpose: The prevalence of nonalcoholic steatohepatitis (NASH) is increasing with the increasing prevalence of childhood obesity. Although NASH has a high risk of progression to liver fibrosis and cirrhosis, few studies have reported noninvasive markers for predicting hepatic fibrosis in children. This study aimed to evaluate and compare the diagnostic accuracies of serologic biomarkers and scoring systems for hepatic fibrosis in obese children with NASH. Methods: A total of 96 children were diagnosed with NASH based on liver biopsy findings and divided into two groups according to the degree of liver fibrosis: mild (stage 0-1) or advanced (stage 2-4). Clinical and laboratory parameters and serum levels of hyaluronic acid and type IV collagen were measured. The aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) score were calculated. Results: Among the noninvasive markers, only serum type IV collagen level and FIB-4 were significantly different between the two groups. The area under the receiver operating curve of each biomarker and scoring system was 0.80 (95% confidence interval [CI]: 0.70-0.90) for type IV collagen at an optimal cutoff of 148 ng/mL (sensitivity 69.8%, specificity 84.6%), followed by 0.69 (95% CI: 0.57-0.83) for APRI, 0.68 (95% CI: 0.56-0.80) for FIB-4, and 0.65 (95% CI: 0.53-0.77) for hyaluronic acid. Conclusion: Type IV collagen as a single noninvasive serologic biomarker for hepatic fibrosis and FIB-4 as a hepatic fibrosis score are beneficial in predicting advanced hepatic fibrosis and determining proper diagnosis and treatment strategies before fibrosis progresses in obese children with NASH.

• BMB Reports
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• 제41권10호
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• pp.685-692
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• 2008

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, non-invasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.

• Mass Spectrometry Letters
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• 제13권1호
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• pp.2-10
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• 2022

Metabolomics makes it possible to analyze the interrelationships between various signaling molecules based on the metabolic pathways involved by using high-resolution devices. This approach can also be used to obtain large-scale metabolic information to identify the relevant pathways for disease diagnosis and prognosis and search for potential biomarkers. In the fields of medicine and forensics, hair analysis is used to detect various metabolites in the body. Hair can be harvested readily in a noninvasive manner and is easier to transport and store than blood and urine. Another advantage from a forensic viewpoint is that hair reflects all the components of body fluids. In addition, because of the unique coating structure of hair, it can be used for measurements without changing or destroying its adsorbed components. In this review, the pretreatments for hair analysis, instrumental conditions and clinical applications are discussed. Especially, the clinical use of hair metabolomics in the diagnosis of various diseases and the limitations of the technique are described.

• Toxicological Research
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• 제32권1호
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• pp.47-56
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• 2016

The identification of biomarkers for the early detection of acute kidney injury (AKI) is clinically important. Acute kidney injury (AKI) in critically ill patients is closely associated with increased morbidity and mortality. Conventional biomarkers, such as serum creatinine (SCr) and blood urea nitrogen (BUN), are frequently used to diagnose AKI. However, these biomarkers increase only after significant structural damage has occurred. Recent efforts have focused on identification and validation of new noninvasive biomarkers for the early detection of AKI, prior to extensive structural damage. Furthermore, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Our previous study suggested that pyruvate kinase M2 (PKM2), which is excreted in the urine, is a sensitive biomarker for nephrotoxicity. To appropriately and optimally utilize PKM2 as a biomarker for AKI requires its complete characterization. This review highlights the major studies that have addressed the diagnostic and prognostic predictive power of biomarkers for AKI and assesses the potential usage of PKM2 as an early biomarker for AKI. We summarize the current state of knowledge regarding the role of biomarkers and the molecular and cellular mechanisms of AKI. This review will elucidate the biological basis of specific biomarkers that will contribute to improving the early detection and diagnosis of AKI.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7315-7319
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• 2013

Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제27권2호
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• pp.79-87
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• 2024

Purpose: Recently, the prevalence of eosinophilic gastrointestinal disease (EGID) has shown an increasing trend worldwide. As the diagnosis of EGID requires invasive endoscopy with biopsy, noninvasive markers for detecting EGID in suspected patients, particularly children, are urgently needed. Therefore, this study aimed to evaluate the diagnostic accuracy of serum eosinophil cationic protein (ECP) beyond peripheral eosinophil counts in pediatric patients with EGID. Methods: Overall, 156 children diagnosed with EGID were enrolled and 150 children with functional abdominal pain disorder (FAPD) were recruited as controls. All participants underwent endoscopic biopsy in each segment of the gastrointestinal (GI) tract and serum ECP measurement, as well as peripheral eosinophil percent and absolute eosinophil count. Results: Comparing EGID (n=156) with FAPD (n=150) patients, serum ECP levels were significantly higher in pediatric patients with EGID than in those with FAPD (25.8±28.6 ㎍/L vs. 19.5±21.0 ㎍/L, p=0.007), while there was no significant difference in peripheral eosinophil percent and absolute eosinophil counts between the two groups. Serum ECP levels were correlated with peripheral eosinophil percent (r=0.593, p<0.001) and the absolute eosinophil count (r=0.660, p<0.001). The optimal cutoff value of serum ECP for pediatric EGID was 10.5 ㎍/mL, with a sensitivity of 69.9% and a specificity of 43.4% with an area under the receiver operating characteristic curve of 0.562. Conclusion: The combination of serum ECP levels and peripheral eosinophil counts, when employed with appropriated thresholds, could serve as a valuable noninvasive biomarker to distinguish between EGID and FAPD in pediatric patients manifesting GI symptoms.

• 대한방사성의약품학회지
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• 제8권1호
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• pp.25-32
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• 2022

Malignant melanoma has an aggressive nature and high metastatic potential that result in one of the highest cancer mortality rates. Over the past three decades, primary and metastatic melanoma incidence has rapidly increased. The recent advances in diagnostic technology have shown promise, but there is still an enormous need for specific detection methods to diagnose malignant melanoma. Positron emission tomography can visualize a particular biomarker of malignant melanoma and promise a noninvasive image of micrometastases. However, the development of PET radiopharmaceuticals remains necessary for diagnosing malignant melanoma by using positron emission tomography. In this review, the history and a general overview of PET radionuclide labeled benzamide derivatives, including their radiosynthesis, in vivo characterization, and evaluation, are provided as imaging agents for malignant melanoma.

• Journal of Animal Science and Technology
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• 제63권2호
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• pp.319-331
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• 2021

Heat stress (HS) causes adverse impacts on pig production and health. A potential biomarker of HS is required to predict its occurrence and thereby better manage pigs under HS. Information about the saliva metabolome in heat-stressed pigs is limited. Therefore, this study was aimed to investigate the effects of acute HS on the saliva metabolome and identify metabolites that could be used as potential biomarkers. Growing pigs (n = 6, 3 boars, and 3 gilts) were raised in a thermal neutral (TN; 25℃) environment for a 5-d adaptation period (CON). After adaptation, the pigs were first exposed to HS (30℃; HS30) and then exposed to higher HS (33℃; HS33) for 24 h. Saliva was collected after adaptation, first HS, and second HS, respectively, for metabolomic analysis using 1H-nuclear magnetic resonance spectroscopy. Four metabolites had significantly variable importance in the projection (VIP > 1; p < 0.05) different levels in TN compared to HS groups from all genders (boars and gilts). However, sex-specific characteristics affected metabolites (glutamate and leucine) by showing the opposite results, indicating that HS was less severe in females than in males. A decrease in creatine levels in males and an increase in creatine phosphate levels in females would have contributed to a protective effect from protein degradation by muscle damage. The results showed that HS led to an alteration in metabolites related to energy and protein. Protection from muscle damage may be attributed to the alteration in protein-related metabolites. However, energy-related metabolites showed opposing results according to sex-specific characteristics, such as sex hormone levels and subcutaneous fat layer. This study had shown that saliva samples could be used as a noninvasive method to evaluate heat-stressed pigs. And the results in this study could be contributed to the development of a diagnostic tool as a noninvasive biomarker for managing heat-stressed pigs.

• Investigative Magnetic Resonance Imaging
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• 제23권4호
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• pp.351-360
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• 2019

Purpose: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx). Materials and Methods: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method. Results: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014). Conclusion: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.