• Journal of Veterinary Science
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• v.22 no.5
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• pp.75.1-75.10
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• 2021

Background: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have important roles in tumor evasion of the immune system. Objectives: This study aimed to assess the diagnostic utility of circulating PD-1 and PD-L1 levels in healthy dogs and dogs with tumors. Methods: Circulating PD-1 and PD-L1 levels in the serum of 71 dogs with tumors were compared with those of 52 healthy dogs by performing enzyme-linked immunosorbent assay (ELISA). Results: The ELISA results revealed higher circulating PD-1 and PD-L1 levels in dogs with tumors (2.9 [2.2-3.7] ng/mL; median [IQR] and 2.4 [1.4-4.4] ng/mL, respectively) than in healthy dogs (2.4 [1.9-3.0] ng/mL; p = 0.012 and 1.4 [0.9-2.1] ng/mL; p < 0.001, respectively). Especially, there was a significant difference in circulating PD-1 levels between healthy dogs and dogs with malignant epithelial tumors (2.4 [1.9-3.0] ng/mL and 3.1 [2.6-4.4] ng/mL, respectively; p < 0.01). In addition, there was a significant difference in circulating PD-L1 levels between healthy dogs and dogs with lymphomas (1.4 [0.9-2.1] ng/mL and 2.7 [1.6-5.8] ng/mL, respectively; p < 0.001). Conclusion: This study indicates that circulating PD-1 and PD-L1 have potential as tumor diagnostic biomarkers in dogs with tumors.

• Journal of Korean Neurosurgical Society
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• v.64 no.3
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• pp.460-468
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• 2021

Objective : Extremely low alanine transaminase (ALT) levels are associated with all-cause mortality in frail elderly individuals; the clinical significance of ALT as a reliable biomarker is now being considered. Predicting mortality with routine tests at the time of diagnosis is important for managing patients after intracranial hemorrhage. We aimed to investigate whether an extremely low ALT level is associated with mortality in the elderly after intracranial hemorrhage. Methods : A retrospective review was performed on 455 patients with intracranial hemorrhage admitted to a university-affiliated tertiary care hospital from February 2014 to May 2019. Multivariate Cox regression analysis was performed for all ages and for each age group to determine whether an extremely low ALT level is an independent predictor of mortality only in the elderly. Results : Overall, 294 patients were enrolled, and the mean age of the subjects was 59.1 years, with 99 (33.8%) aged ≥65 years. The variables associated with all-cause mortality in all subjects were age, C-reactive protein (CRP) levels, hemoglobin (Hb) levels (<11 g/dL), and initial Glasgow coma scale (GCS) scores. In young patients, CRP, low Hb levels, and initial GCS scores were significantly associated with all-cause mortality. However, in the elderly (≥65 years), the variables significantly associated with all-cause mortality were extremely low levels of ALT (<10 U/L) (adjusted hazard ratio, 3.313; 95% confidence interval, 1.232-8.909; p=0.018) and initial GCS scores. Conclusion : Extremely low ALT level (<10 U/L) at the time of diagnosis is a significant risk factor for all-cause mortality in the elderly after intracranial hemorrhage.

• 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.1
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• pp.43-49
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• 2023

Purpose: The cow's milk-related-symptom-score (CoMiSS) tool was developed as an awareness tool for the assessment of cow's milk-related symptoms in infants or children. Fecal calprotectin (FC) is a noninvasive biomarker of gut inflammation that can be measured in serum and stool. This study aimed to investigate the relationship between FC levels and CoMiSS scores in infants with cow's milk protein allergy. Methods: Infants (aged 6-12 months) who were allergic to cow's milk protein were enrolled prospectively. Following completion of the CoMiSS scoring, the infants were divided into group 1 (positive CoMiSS scores ≥12) and group 2 (negative CoMiSS scores <12). FC was measured using immunoassay. Results: Of the 120 infants enrolled in this study, 60 (50.0%) had positive CoMiSS scores (group 1), while 60 (50.0%) had negative scores (group 2). The mean FC level was higher in the infants in group 1 than those in group 2 (2,934.57 ㎍/g vs. 955.13 ㎍/g; p<0.001). In addition, there was a positive correlation between FC and CoMiSS scores (R=0.168, p<0.0001). A FC level of 1,700 ㎍/g provided a sensitivity of 98.3%, specificity of 93.3%, and accuracy of 95.8% for the diagnosis of cow's milk protein allergy (CMPA). Conclusion: FC measurement may have a role in the assessing infants with CMPA.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.945-953
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• 1996

Background : Many acute and chronic lung diseases including pneumoconiosis are characterized by the presence of increased numbers of activated macrophages. These macrophages generate several inflammatory cell chemoattractants, by which neutrophil migrate from vascular compartment to the alveolar space. Recruited neutrophils secrete toxic oxygen radicals or proteolytic enzymes and induce inflammatory response. Continuing inflammatory response results in alteration of the pulmonary structure and irreversible fibrosis. Recently, a polypeptide with specific neutrophil chemotactic activity, interleukin-8(IL-8), has been cloned and isolated from a number of cells including : monocytes, macrophages and fibroblasts. IL-1 and/or TNF-${\alpha}$ preceded for the synthesis of IL-8, and we already observed high level of IL-1 and TNF-${\alpha}$ in the pneumoconioses. So we hypothesized that IL-8 may be a central role in the pathogenesis of pneumoconiosis. In order to evaluate the clinical utility of IL-8 as a biomarker in the early diagnosis of pneumoconiosis, we investigated the increase of IL-8 in the pneumoconiotic patient and the correlation between IL-8 level and progression of pneumoconiosis. Method : We measured IL-8 in the serum of 48 patients with pneumoconiosis and 16 persons without dust exposure history as a control group. Pneumoconiotic cases were divided into 3 groups according to ILO Classification : suspicious group(n=16), small opacity group(n=16) and large opacity group(n=16). IL-8 was measured by a sandwich enzytne immunoassay technique. All data were expressed as the $mean{\pm}standard$ deviation. Results: 1) The mean value of age was higher in the small opacity and large opacity group than comparison group, but smoking history was even. Duration of dust exposure was not different among 3 pneumoconiosis groups. 2) IL-8 level was $70.50{\pm}53.63pg/m{\ell}$ in the suspicious group, $107.50{\pm}45.88pg/m{\ell}$ in the small opacity group, $132.50{\pm}73.47pg/m{\ell}$ in the large opacity group and $17.85{\pm}33.85pg/m{\ell}$ in the comparison group. IL-8 concentration in all pneumoconiosis group was significant higher than that in the comparison group(p<0.001). 3) IL-8 level tended to increase with the progression of pneumoconiosis. Multiple comparison test using Anova/Scheffe analysis showed a significant difference between suspicious group and large opacity group(p<0.05). 4) The level of IL-8 was correlated with the progression of pneumoconiosis(r=0.4199, p<0.05). Conclusion : IL-8 is thought to be a good biomarker for the early diagnosis of pneumoconiosis.

• Childhood Kidney Diseases
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• v.18 no.1
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• pp.36-41
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• 2014

Purpose: Urinary tract infections (UTIs) are the most common source of bacterial infections in infants and young children. Accurate diagnosis and treatment is important because of their association with renal scarring, which can lead to complications. Urine endothelin-1 (ET-1) is the major renal isoform produced and released by renal mesangial cells in response to glomerular injury. This study aimed to investigate whether urinary levels of ET-1 can be used as a biomarker for UTI diagnosis. Method: We conducted a prospective study using medical records of 70 patients below the age of 18 years, who visited Chung-Ang University Hospital from July 2012 to July 2013. We classified the patients into the UTI and control groups based on urine culture studies. The UTI group was further divided into upper and lower UTI groups using 99m-Technetium dimercaptosuccinic acid scintigraphy. Urine ET-1 was measured using enzyme linked immunosorbent assay with 0.3 mL urine. Results: The UTI and control groups were comprised of 45 and 25 patients, respectively. Mean urine ET-1 levels were significantly higher in the UTI group than in the control group ($1.41{\pm}0.35$ pg/mL vs. $0.33{\pm}0.07$ pg/mL, P =0.04). There was no significance difference in the quantitative value between the upper and lower UTI groups (P =0.552). There was no correlation between urine ET-1 and serum C-reactive protein (Pearson correlation [R]=0.24), urine ET-1 and serum white blood cell count (R=0.19). Conclusion: Our study suggests that urine ET-1 can be used for early diagnosis of UTI in children.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3931-3936
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• 2013

Background: Iran is a country with very high incidences of stomach cancer, especially in Northern parts. Here we assessed prognostic value of serum screening biomarkers among people >50 years old for early detection of precancerous lesions in a hot spot for gastric carcinoma in Guilan Province, North Iran. Methods: A cross-sectional population-based survey was conducted on 1,390 residents of Lashtenasha city with the mean age (SD) of 61.8 (9.02) years old (50.8% females) to assess the association of gastrin and the pepsinogen (PG) I/II ratio with premalignant gastric lesions. Blood samples were taken for CBC, blood group, and serologic exams (PGI, PGII, and gastrin 17) from each subject. Expert gastroenterologists performed upper GI endoscopy and ROC curves were generated to determine appropriate cutoff points. Results: Mean values of PGI, PGII, PGI/PGII and gastrin were significantly different between patients with and without atrophy or metaplasia (P<0.05). To diagnose atrophy and intestinal metaplasia, a significantly higher AUC was observed for the PGI/PGII ratio (70 and 72%, respectively) compared to the PGI (56, 55%), PGII (63, 64%) and gastrin (59, 61%) (all p<0.001). Conclusions: Biomarker tests such as the PGI/II ratio can be used in the screening and diagnosis of subjects at high gastric cancer risk in our region.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.2
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• pp.185-191
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• 2020

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = -0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

• Journal of the Korean Applied Science and Technology
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• v.36 no.4
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• pp.1188-1197
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• 2019

Exposure to stress can lead to sympathetic hyperactivity, which include a systemic disease with lesions in a broad spectrum of organs and a psychiatric condition. The purpose aimed to evaluate the effect of the korea ginger essential oil on stress hormone and brain tissue response in chronic mild stress-induced rats model of sympathetic hyperactivity. Evaluation method carried out cytotoxicity assessment and component analysis, what observe the effects based on serum biomarker and histopathological analysis of brain tissue. As this time, the korea ginger essential oil was treatment at doses of 100 nl/㎖ for 2 weeks after make a chronic mild stress-induced rats model of sympathetic hyperactivity. As a result, the korea ginger essential oil was not toxic at less than 100 nl/㎖, contents of 6-gingerol was 345 ppm. Compared to the control rats, the korea ginger essential oil treatments significantly reduced the serum concentrations of stress hormone (i.e., ACTH, corticosterone, melatonin). Furthermore, The korea ginger essential oil treatments effectively preserved the TH-immune response was occasionally interrupted in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNpc). The results indicate that the korea ginger essential oil improved sympathetic hyperactivity. Thus, the korea ginger may be a novel material of aroma oils for the management of sympathetic hyperactivity.

• The Korea Journal of Herbology
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• v.30 no.4
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• pp.81-88
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• 2015

Objectives : The aim of present study was to evaluate the beneficial effect of Scutellariae Radix (SR) and Scutellariae Radix EtOH-heated at 200℃ (SR200) using lipopolysaccharide (LPS) treated intestine of mice.Methods : Extract of SR and SR200 were orally administrated. Their effects were compared with vehicletreated LPS and normal groups. Subsequently, we measured reactive oxygen species (ROS) and nitric oxide in the serum and western blotting in the intestine.Results : The average weight in LPS treated (Vehicle) group was lowered significantly compare to that in non-treated normal group and this weight loss in the vehicle group was effectively prevented by the administration of SR and SR200 respectively. The increased oxidative stress biomarker levels such as reactive oxygen species (ROS) and nitric oxide (NO) in the serum was markedly decreased by treated with SR200. The decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) induced by LPS injection were significantly restored by both SR and SR200 treatment. Moreover, increased inflammatory mediators and cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in the LPS treated vehicle mice were significantly decreased through down-regulation c-JUN through reduction of oxidative stress.Conclusions : SR and SR200 could have benefit effect through down-regulation of abnormal oxidative stress in LPS induced intestine injury mice. Moreover, The anti-inflammatory activity of SR200 extract was better than SR extract in the LPS induced intestine injury mice.