• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.19-24
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• 2016

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The exploration of new biomarkers with high sensitivity and specificity for early diagnosis of AMI therefore becomes one of the primary task. In the current study, we aim to detect whether there is any heart specific long noncoding RNA (lncRNA) releasing into the circulation during AMI, and explore its function in the neonatal rat cardiac myocytes injury induced by $H_2O_2$. Our results revealed that the cardiac-specific lncRNA MHRT (Myosin Heavy Chain Associated RNA Transcripts) was significantly elevated in the blood from AMI patients compared with the healthy control ($^*p<0.05$). Using an in vitro neonatal rat cardiac myocytes injury model, we demonstrated that lncRNA MHRT was upregulated in the cardiac myocytes after treatment with hydrogen peroxide ($H_2O_2$) via real-time RT-PCR (qRT-PCR). Furthermore, we knockdowned the MHRT gene by siRNA to confirm its roles in the $H_2O_2$-induced cardiac cell apoptosis, and found that knockdown of MHRT led to significant more apoptotic cells than the non-target control ($^{**}p<0.01$), indicating that the lncRNA MHRT is a protective factor for cardiomyocyte and the plasma concentration of MHRT may serve as a biomarker for myocardial infarction diagnosis in humans AMI.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.193-201
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• 2006

Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.44 no.4
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• pp.174-181
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• 2018

Objectives: The number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing, but treatment remains controversial. Published papers and systematic reviews have suggested that surgical treatment is effective in patients with MRONJ. The purpose of this study was to determine whether preoperative University of Connecticut Osteonecrosis Numerical Scale (UCONNS), other serologic biomarkers, and size of necrosis are prognostic factors for outcome of surgical treatment in MRONJ. Materials and Methods: From January 2008 to December 2016, 65 patients diagnosed with MRONJ at the Department of Oral and Maxillofacial Surgery in College of Dentistry, Dankook University who required hospitalization and surgical treatment were investigated. Patient information, systemic factors, and UCONNS were investigated. In addition, several serologic values were examined through blood tests one week before surgery. The size of osteolysis was measured by panoramic view and cone-beam computed tomography in all patients. With this information, multivariate logistic regression analysis with backward elimination was used to examine factors affecting postoperative outcome. Results: In multivariate logistic analysis, higher UCONNS, higher C-reactive protein (CRP), larger size of osteolysis, and lower serum alkaline phosphate were associated with higher incidence of incomplete recovery after operation. This shows that UCONNS, CRP, serum alkaline phosphate, and size of osteolysis were statistically significant as factors for predicting postoperative prognosis. Conclusion: This study demonstrated that CRP, UCONNS, serum alkaline phosphate, and size of osteolysis were statistically significant factors in predicting the prognosis of surgical outcome of MRONJ. Among these factors, UCONNS can predict the prognosis of MRONJ surgery as a scale that includes various influencing factors, and UCONNS should be used first as a predictor. More aggressive surgical treatment and more definite surgical margins are needed when the prognosis is poor.

• Nutrition Research and Practice
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• v.11 no.4
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• pp.334-339
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• 2017

BACKGROUND/OBJECTIVES: Telomere length is a useful biomarker for determining general aging status. Some studies have reported an association between alcohol consumption and telomere length in a general population; however, it is unclear whether the alcohol flush reaction, which is an alcohol-related trait predominantly due to acetaldehyde dehydrogenase deficiency, is associated with telomere length. This cross-sectional study aimed to evaluate the associations of alcohol consumption and alcohol flush reaction with leukocyte telomere length (LTL). SUBJECTS/METHODS: The study included 1,803 Korean adults. Participants provided blood specimens for LTL measurement assay and reported their alcohol drinking status and the presence of an alcohol flush reaction via a questionnaire-based interview. Relative LTL was determined by using a quantitative polymerase chain reaction. Statistical analysis used multiple linear regression models stratified by sex and age groups, and potential confounding factors were considered. RESULTS: Age-specific analyses showed that heavy alcohol consumption (> 30 g/day) was strongly associated with a reduced LTL in participants aged ${\geq}65years$ (P < 0.001) but not in younger participants. Similarly, the alcohol flush reaction was associated with a reduced LTL only in older participants who consumed > 15 g/day of alcohol (P < 0.01). No significant alcohol consumption or alcohol flush reaction associations with LTL were observed in the sex-specific analyses. CONCLUSIONS: The results suggest that older alcohol drinkers, particularly those with the alcohol flush reaction, may have an accelerated aging process.

• Clinical and Experimental Pediatrics
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• v.64 no.7
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• pp.347-354
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• 2021

Background: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a valuable biomarker of urinary tract infection (UTI) in children. Purpose: This study aimed to compare the diagnostic accuracy of urinary NGAL (uNGAL) with those of serum C-reactive protein (CRP) and white blood cell (WBC) count for predicting UTI and acute pyelonephritis (APN) in febrile children. Methods: The medical charts of children undergoing uNGAL measurements between November 2017 and August 2019 were retrospectively reviewed. Patients with a suspected or diagnosed UTIs were included. The diagnostic accuracies of uNGAL, serum CRP, and WBC count for detecting UTI and APN were investigated. Independent predictors of UTI and APN were investigated using multivariable logistic regression analyses. Results: A total of 321 children were enrolled in this study. The uNGAL levels were higher in the UTI group (n=157) than in the non-UTI group (n=164) (P<0.05). Among children with a UTI, uNGAL levels were higher in the APN group (n=70) than, the non-APN group (n=87) (P<0.05). In the multivariate analysis, uNGAL was independently associated with UTI and APN (both P<0.05). Serum CRP and WBC count were not correlated with the presence of UTI and APN. Receiver operating curve analyses showed that the uNGAL level had the highest area under the curve (AUC) for predicting UTI and APN, respectively (AUC, uNGAL vs. CRP vs. WBC count, 0.860 vs. 0.608 vs. 0.669 for UTI; 0.780 vs. 0.680 vs. 0.639 for APN, all P<0.05, respectively). The predictive values and likelihood ratios of uNGAL were superior to those of serum CRP and WBC count for detecting UTI and APN at each cutoff level. Conclusion: UNGAL may be more useful than serum CRP and WBC count for identifying and assessing UTI in febrile children.

• Animal Bioscience
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• v.34 no.11
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• pp.1839-1848
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• 2021

Objective: The objective of the present study was to investigate the comparative effects of dietary functional nutrients including glutamine (Gln), chromium picolinate (Cr picolinate), vitamin C (Vit C), betaine (Bet), and taurine (Tau) on growth performance, meat quality, immune responses, and stress biomarkers in broiler chickens raised under heat stress conditions. Methods: A total of 420 21-d-old Ross 308 male broiler chickens (initial body weight = 866±61.9 g) were randomly allotted to 1 of 7 treatment groups with 6 replicates. One group was kept under thermoneutral conditions and was fed a basal diet (PC, positive control). Other 6 groups were exposed to a cyclic heat stress condition. One of the 6 groups was fed the basal diet (NC, negative control), whereas 5 other groups were fed the basal diet supplemented with 0.5% Gln, 500 ppb Cr picolinate, 250 mg/kg Vit C, 0.2% Bet, or 1.0% Tau. The diets and water were provided ad libitum for 21 d. Results: Broiler chickens in NC group had decreased (p<0.05) growth performance and immune responses measured based on cutaneous basophil hypersensitivity (CBH), but increased (p<0.05) stress responses measured based on feather corticosterone concentrations and blood heterophil:lymphocyte than those in PC group. However, none of dietary functional nutrients had a positive effect on growth performance of broiler chickens. Dietary supplementation of 250 mg/kg Vit C improved (p<0.05) CBH responses of broiler chickens, but other functional nutrients had no such an improvement in CBH responses. All functional nutrients decreased (p<0.05) stress responses of broiler chickens. Conclusion: Functional nutrients including Gln, Cr picolinate, Vit C, Bet, and Tau at the supplemental levels used in this study decrease stress responses of broiler chickens to a relatively similar extent. However, this reduction in stress responses could not fully ameliorate decreased productive performance of broiler chickens raised under the current heat stress conditions.

• Journal of Medicine and Life Science
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• v.17 no.3
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• pp.65-73
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• 2020

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease of the cerebral small blood vessels caused by mutations in the NOTCH3 gene on chromosome 19. Although CADASIL was known as a rare disease, recent research has suggested that the NOTCH variants could be found frequently even in the general population. The main clinical features included recurrent stroke, migraine, psychiatric symptoms, and progressive cognitive decline. On brain magnetic resonance imaging, patients with CADASIL showed multifocal white matter hyperintensity lesions, lacunar infarcts, microbleeds, and brain atrophy. Among them, lacunar infarcts and brain atrophy are important in predicting the clinical outcomes of patients with CADASIL. In the Jeju National University Hospital, we have diagnosed 213 CADASIL patients from 2004 to 2020. Most NOTCH3 mutations were located in exon 11 (94.4%), and p.Arg544Cys was the most common mutation. The mean age at diagnosis was 61.0±12.8 years. The most common presenting symptoms were ischemic stroke (24.4%), followed by cognitive impairment(15.0%), headache (8.9%), and dizziness(8.0%). Although the exact prevalence of CADASIL in Jeju is still unknown, the disease prevalence could be as high as 1% of the population considering the prevalence reported in Taiwan. Therefore, it is necessary to discover efficient biomarkers and genetic tests that can accurately screen and diagnose patients suspected of having CADASIL in this region. Ultimately, it is urgent to explore the exact pathogenesis of the disease to identify leading substances of treatment potential, and for this, multi-disciplinary research through active support from the Jeju provincial government as well as the national government is essential.

• Journal of Veterinary Science
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• v.21 no.6
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• pp.81.1-81.10
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• 2020

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

• Parasites, Hosts and Diseases
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• v.61 no.1
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• pp.42-52
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• 2023

The genus Babesia includes parasites that can induce human and animal babesiosis, which are common in tropical and subtropical regions of the world. The gut microbiota has not been examined in hamsters infected by Babesia duncani. Red blood cells infected with B. duncani were injected into hamsters through intraperitoneal route. To evaluate the changes in gut microbiota, DNAs were extracted from small intestinal contents, acquired from hamsters during disease development. Then, the V4 region of the 16S rRNA gene of bacteria was sequenced using the Illumina sequencing platform. Gut microbiota alternation and composition were assessed according to the sequencing data, which were clustered with >97.0% sequence similarity to create amplicon sequence variants (ASVs). Bacteroidetes and Firmicutes were made up of the major components of the gut microbiota in all samples. The abundance of Bacteroidetes elevated after B. duncani infection than the B. duncani-free group, while Firmicutes and Desulfobacterota declined. Alpha diversity analysis demonstrated that the shown ASVs were substantially decreased in the highest parasitemia group than B. duncani-free and lower parasitemia groups. Potential biomarkers were discovered by Linear discriminant analysis Effect Size (LEfSe) analysis, which demonstrated that several bacterial families (including Muribaculaceae, Desulfovibrionaceae, Oscillospiraceae, Helicobacteraceae, Clostridia UGG014, Desulfovibrionaceae, and Lachnospiraceae) were potential biomarkers in B. duncani-infected hamsters. This research demonstrated that B. duncani infectious can modify the gut microbiota of hamsters.

• Journal of Korean geriatric psychiatry
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• v.16 no.1
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• pp.17-23
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• 2012

The diagnosis of Alzheimer's disease (AD) is still obscure even to specialists. To improve the diagnostic accuracy, to find at-risk people as early as possible, to predict the efficacy or adverse reactions of pharmacotherapy on an individual basis, to attain more reliable results of clinical trials by recruiting better defined participants, to prove the disease-modifying ability of new candidate drugs, to establish prognosis-based therapeutic plans, and to do more, is now increasing the need for biomarkers for AD. Among AD-related biochemical markers, cerebrospinal beta-amyloid and tau have been paid the most attention since they are materials directly interfacing the brain interstitium and can be obtained through the lumbar puncture. Level of beta-amyloid is reduced whereas tau is increased in cerebrospinal fluid of AD patients relative to cognitively normal elderly people. Remarkably, such information has been found to help predict AD conversion of mild cognitive impairment. Despite inconsistent findings from previous studies, plasma beta-amyloid is thought to be increased before the disease onset, but show decreasing change as the disease progress. Regarding other peripheral biochemical markers, omics tools are being widely used not only to find useful biomarkers but also to generate novel hypotheses for AD pathogenesis and to lead new personalized future medicine.