• Journal of Veterinary Clinics
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• v.36 no.2
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• pp.102-105
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• 2019

Nitrotyrosine was found to be dependent on the severity of myxomatous mitral valve disease (MMVD). However, a correlation of serum nitrotyrosine concentration in dogs with MMVD and the progression of the disease has not been investigated. This study compared changes in serum nitrotyrosine concentration with the progression of MMVD. Nine client-owned dogs were recruited for the study. Dogs were classified by measuring the amount of regurgitation using echocardiography into mild, moderate, or severe MMVD groups. Serum nitrotyrosine concentration was measured by an enzyme-linked immunosorbent assay test. Serum nitrotyrosine concentration was significantly higher at 180 days than at 0 day (P < 0.05). However, serum nitrotyrosine concentration at 360 days was lower than that at 180 days (P < 0.05). Serum nitrotyrosine concentration at 540 days was lower than at 180 days (P < 0.05). There was no correlation between serum nitrotyrosine and left atrial to aortic root diameter ratio (LA/Ao ratio) (n = 33, $R^2=0.003$, P = 0.759). Also, there was no correlation between serum nitrotyrosine and vertebral heart score (VHS) (n = 33, $R^2=0.026$, P = 0.368) and left ventricular end-diastolic diameter, normalized for body weight by the formula (LVEDDN) (n = 33, $R^2=0.053$, P = 0.196). The results of the study suggest that the progression of MMVD is correlated with changes in serum nitrotyrosine concentration, which shows potential for use as a cardiac biomarker which can be used to analyze the progression of disease in MMVD.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2563-2566
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• 2013

Background: Interleukin-33 (IL-33) has recently been implicated in tumor immunity. The aim of this study was to explore the clinical role of serum IL-33 in patients with non-small-cell lung cancer (NSCLC). Methods: Sera collected from 250 healthy volunteers (HV), 256 patients with benign lung diseases (BLD) and 262 NSCLC cases were subjected to IL-33 ELISA and relationships between serum IL-33 and clinical characteristics were evaluated. Results: Circulating IL-33 levels were higher in the NSCLC group in comparison with the HV and BLD groups (p<0.001). Using a cut-off level 68 pg/ml (95% specificity in the HV group), IL-33 showed a good diagnostic performance for NSCLC. Multivariate survival analysis indicated that serum IL-33 was an independent prognostic factor in the entire NSCLC group [hazards ratio (HR) = 0.64 for low versus high IL-33 levels, 95% confidence interval (CI) 0.50-0.82; p<0.001] and in 165 selected patients with locally advanced or metastatic disease receiving chemoradiotherapy or chemotherapy (HR 0.70, 95% CI 0.52-0.94; p=0.013). Conclusions: IL-33 is a promising potential diagnostic and prognostic marker in NSCLC, independent of the therapeutic intervention.

• Toxicological Research
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• v.27 no.1
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• pp.19-23
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• 2011

It has been proposed that acute phase response can be a mechanism by which inhaled particles exert adverse effects on the cardiovascular system. Although some of the human acute phase proteins have been widely studied as biomarkers of systemic inflammation or cardiovascular diseases, there are only a few studies that investigated the role of serum amyloid P (SAP), a major acute phase protein in mice. In this study, we investigated the changes in SAP, following inhalation exposure to nickel hydroxide nanoparticles (nano-NH). We conducted 1) acute (4 h) exposure to nano-NH at 100, 500, and $1000\;{\mu}g/m^3$ and 2) sub-acute (4h/d for 3d) exposure at $1000\;{\mu}g/m^3$, then measured serum SAP protein levels along with hepatic Sap mRNA levels. The results show that inhaled nano-NH can induce systemic acute phase response indicated by increased serum SAP levels and hepatic Sap mRNA levels. To the best of our knowledge, this is the first study showing induction of SAP in response to repeated particle exposure, and the results suggest that SAP can be used as a biomarker for systemic inflammation induced by inhaled particles.

• Annals of Clinical Neurophysiology
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• v.23 no.1
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• pp.46-52
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• 2021

Background: We aimed to investigate candidates for serological biomarkers of neuropathic pain in individuals with neuromyelitis optica spectrum disorder (NMOSD). Methods: We analyzed 38 sera samples from 38 participants with NMOSD in National Cancer Center. Neuropathic pain was evaluated using the painDETECT questionnaire. Pain with neuropathic components (painDETECT score ≥ 13) was observed in 22 participants, among whom 17 had definite neuropathic pain (painDETECT score ≥ 19). The remaining 16 participants had non-neuropathic pain (painDETECT score < 13). Serum glial fibrillary acidic protein (GFAP) levels were assessed using a single-molecule array assay. Several cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, and IL-17A, were measured by a multiplex bead-based immunoassay. Results: In comparison of NMOSD participants with neuropathic pain components (or definite neuropathic pain) and those with non-neuropathic pain, the absolute values of serum GFAP, TNF-α, IL-6, and IL-10 levels were higher in participants with neuropathic pain components (or definite neuropathic pain), but these findings did not reach statistical significance. Conclusions: Further larger-scale investigations to find reliable serological biomarkers for neuropathic pain in NMOSD are warranted.

• Korean Journal of Veterinary Research
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• v.57 no.1
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• pp.17-21
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• 2017

The aim of this study was to compare serum nitrotyrosine concentrations in healthy dogs with those in dogs with myxomatous mitral valve disease (MMVD). Fifty client-owned dogs were included in this study. Based on echocardiographic results, dogs were categorized into healthy (control), mild-, moderate-, and severe-MMVD groups. Serum nitrotyrosine concentrations were determined from enzyme-linked immunosorbent assays. No significant difference between control dogs and dogs with mild MMVD was detected (p = 0.31). However, dogs with moderate MMVD had significantly higher serum concentrations of nitrotyrosine (p = 0.04) than that in controls, and dogs with severe MMVD had significantly lower serum concentrations of nitrotyrosine (p = 0.03) than that in moderate MMVD dogs. There were negative correlations in the association of serum nitrotyrosine with age (n = 30, $R^2=0.067$, p = 0.27), left atrial-to-aortic root diameter ratio (n = 30, $R^2=0.02$, p = 0.57), and platelet count (n = 30, $R^2=0.39$, p = 0.003); however, only the platelet correlation was significant. Among dogs with MMVD, there was no significant difference in serum nitrotyrosine concentration between males and females. The results of this study suggest that tyrosine nitration end-products might be potential biomarkers for the detection of MMVD in dogs.

• Journal of Veterinary Science
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• v.22 no.6
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• pp.79.1-79.14
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• 2021

Background: In contrast to human medicine, only a small number of serum tumor markers are established in veterinary medicine even though they are a non-invasive diagnostic tool. Objectives: This study examined whether survivin could be suitable as a potential canine serum tumor marker. Methods: This study measured the serum survivin concentrations of dogs with mammary tumors (n = 33), squamous cell carcinoma (n = 9), soft-tissue sarcoma (n = 18) and multicentric lymphoma (n = 22), using a commercially available, competitive immunoassay kit (BlueGene). The serum survivin concentrations were compared with those of a healthy control group (n = 20) and a control group of dogs with non-neoplastic diseases (n = 17). Results: Dogs with malignant tumors had serum survivin concentrations between 15 and 5,906 pg/mL (median, 72 pg/mL), those in the healthy group ranged from 7 to 99 pg/mL (median, 21 pg/mL) and those in the group of dogs suffering from non-neoplastic diseases from 15 to 93 pg/mL (median, 42 pg/mL). The differences in the survivin concentrations between the healthy dogs and dogs with malignant tumors and between the dogs with non-neoplastic diseases and those with malignant tumors were significant (p < 0.001 and p = 0.006, respectively). Conclusions: The serum survivin concentrations in dogs with malignant tumors, with some exceptions, are higher than in dogs with benign tumors and dogs that do not suffer from a malignancy. Therefore, survivin can provide information on the presence of malignant tumors and be used as a tumor marker in dogs.

• Tuberculosis and Respiratory Diseases
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• v.84 no.3
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• pp.200-208
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• 2021

Background: Hypersensitivity pneumonitis (HP) is an increasingly recognized form of diffuse parenchymal lung disease. Krebs von den Lungen-6 (KL-6) is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with interstitial lung diseases (ILD). Serum KL-6/MUC1 levels have been demonstrated to be useful for the evaluation of various ILD. To determine the role of circulating KL-6 in evaluating the disease activity and management of HP. Methods: An observational cross-sectional study was conducted on 51 patients with HP and 20 healthy controls. Serum KL-6 levels were measured in both groups. Patients were further assessed based on chest high-resolution computed tomography (HRCT), pulmonary function test, 6-minute walk test, echocardiography, bronchioalveolar lavage, and/or transbronchial biopsy. Patients were divided into the fibrotic and non-fibrotic groups according to the HRCT findings. Results: The median serum KL-6 levels were significantly higher in HP patients as compared to the control group. The median serum KL-6 levels were found to be higher in the non-fibrotic HP group (1,900 IU/mL) as compared to the fibrotic group (1,200 IU/mL). There was a significant inverse correlation between serum KL-6 serum level and the dose of steroids as well as the duration of steroid therapy. Conclusion: The presence of higher KL-6 levels in the non-fibrotic HP group implies its enhanced production by regenerating pneumocytes in response to alveolar injury. The significant association between serum KL-6 levels and the dose and the duration of steroid therapy emphasizes the significant role of steroids in the stabilization of the disease.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.29 no.1
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• pp.42-49
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• 2019

Objective: Chronic obstructive pulmonary disease(COPD) is characterized by persistent airflow limitations associated with chronic inflammatory response due to noxious particles or gases in the lung. Iron deficiency is associated with chronic inflammation, such as COPD. The aim of this study was to evaluate the relationship among iron deficiency, iron homeostasis, and inflammation in retired miners with COPD. Methods: The serum levels of ferritin, soluble transferrin receptor(sTfR), and transferrin saturation(TSat) as biomarkers for iron deficiency and high-sensitivity C-reactive protein(hsCRP) as a biomarker for inflammation and hepcidin as a biomarker for iron homeostasis were measured in 93 male subjects. Iron deficiency was defined as any one or more of (1) sTfR>28.1 nmol/L, (2) TSat<16%, and (3) ferritin< $12{\mu}g/L$. Results: Iron deficiency was found 28% of the study subjects. Median levels of serum hsCRP was significantly increased related to airflow limitation of COPD(GOLD 1, $0.09{\mu}g/dL$ vs. GOLD 2, $0.17{\mu}g/dL$ vs. GOLD $3{\leq}$, $0.30{\mu}g/dL$, p=0.010), and was positively correlated with hepcidin(p=0.009). Mean level of serum hepcidin was lower in COPD subjects with iron deficiency(p=0.004) and serum levels of hepcidin was negatively correlated with %$FEV_1$ predicted(p=0.030). Conclusions: These results suggest that high serum levels of hepcidin are related to severe airflow limitation or inflammation and can decrease iron availability, regardless of iron status.

• Animal Bioscience
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• v.36 no.9
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• pp.1336-1349
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• 2023

Objective: The study was conducted to screen differentially expressed miRNAs in sows at early pregnancy by high-throughput sequencing and explore its mechanism of action on embryo implantation. Methods: The blood serum of pregnant and non-pregnant Landrace×Yorkshire sows were collected 14 days after artificial insemination, and exosomal miRNAs were purified for high throughput miRNA sequencing. The expression patterns of 10 differentially expressed (DE) miRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The qRT-PCR quantified the abundance of serum exosomal miR-192 in pregnant and control sows, and the diagnostic power was assessed by receiver operating characteristic (ROC) analysis. The target genes of DE miRNAs were predicted with bioinformatics software, and the functional and pathway enrichment analysis was performed on gene ontology and the Kyoto encyclopedia of genes and genomes terms. Furthermore, a luciferase reporter system was used to identify the target relation between miR-192 and integrin alpha 4 (ITGA4), a gene influencing embryo implantation in pigs. Finally, the expression levels of miRNAs and the target gene ITGA4 were analyzed by qRT-PCR, and western blot, with the proliferation of BeWo cells detected by cell counting kit-8 (CCK-8). Results: A total of 221 known miRNAs were detected in the libraries of the pregnant and non-pregnant sows, of which 55 were up-regulated and 67 were down-regulated in the pregnant individuals compared with the non-pregnant controls. From these, the expression patterns of 10 DE miRNAs were validated. The qRT-PCR analysis further confirmed a significantly higher expression of miR-192 in the serum exosomes extracted from pregnant sows, when compared to controls. The ROC analysis revealed that miR-192 provided excellent diagnostic accuracy for pregnancy (area under the ROC curve [AUC]=0.843; p>0.001). The dual-luciferase reporter assay indicated that miR-192 directly targeted ITGA4. The protein expression of ITGA4 was reduced in cells that overexpressed miR-192. Overexpression of miR-192 resulted in the decreased proliferation of BeWo cells and regulated the expression of cell cycle-related genes. Conclusion: Serum exosomal miR-192 could serve as a potential biomarker for early pregnancy in pigs. miR-192 targeted ITGA4 gene directly, and miR-192 can regulate cellular proliferation.

• Journal of Applied Biological Chemistry
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• v.52 no.4
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• pp.170-173
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• 2009

Vitellogenin (Vtg) is found in the serum of both female and male fish that have been exposed to environmental endocrine disrupters or estrogen hormones, and is used as a biomarker for such contamination. In our current study antibodies raised against the purified flatfish Vtg were tested for their reactivity on immunoblots to flatfish and carp Vtg, and also to a Vtg protein fragment produced in E. coli. Polyclonal antibodies raised against purified flatfish Vtg reacted well with Vtg in the serum of flatfish and carp induced with $17{\beta}$-estradiol, but not with the Vtg protein fragment produced in E. coli.