• Mass Spectrometry Letters
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• 제5권4호
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• pp.110-114
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• 2014

The method of direct mass spectrometry profiling is reliable and reproducible for the rapid identification of clinical isolates of bacteria and fungi. This is the first study evaluating the approach of MALDI-TOF mass spectrometry profiling for rapid identification of carbapenemase-resistant enterobacteriaceae (CRE). Proof of concept was achieved by the discrimination of CRE using MALDI Biotyper MS based on the protein. This profiling appears promising by the visual observation of consistent unique peaks, albeit low intensity, that could be picked up from the mean spectra (MSP) method. The Biotyper MSP creation and identification methods needed to be optimized to provide significantly improved differences in scores to allow for subspecies identification with and without carbapenemases. These spectra were subjected to visual peak picking and in all cases; there were pertinent differences in the presence or absence of potential biomarker peaks to differentiate isolates. We also evaluated this method for potential discrimination between different carbapenemases bacteria, utilizing the same strategy. Based on our data and pending further investigation in other CREs, MALDI-TOF MS has potential as a diagnostic tool for the rapid identification of even closely related carbapenemases but would require a paradigm shift in which Biotyper suppliers enable more flexible software control of mass spectral profiling methods.

• 한국산업보건학회지
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• 제30권2호
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• pp.196-204
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• 2020

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. Increasing oxidative stress associated with COPD. The aim of this study was to evaluate the influencing factors of biomarkers for oxidative stress in retired miners with COPD. Methods: The levels of total peroxide(TPx), total antioxidant capacity(TAC), and oxidative stress index(TPx/TAC ratio, OSI) in plasma as biomarkers for oxidative stress, serum C-reactive protein(CRP) as a biomarker for inflammation, and general characteristics were measured in 93 male subjects with COPD. COPD was defined as post bronchodilator FEV₁/FVC<0.7 by spirometry. Results: Mean levels of TPx(p=0.013), TAC(p=0.010), OSI(p=0.040), and CRP(p=0.024) were higher in current smokers. Levels of TPx(β=0.445, p<0.001), TAC(β=0.490, p<0.001), and OSI(β=0.351, p<0.001) were related to CRP levels, and CRP levels were related to %FEV₁ predicted(β=-0.295, p=0.003) and current smoking(β=0.214, p=0.032). Conclusions: These results suggest that oxidative stress was related to inflammation, and inflammation were related to decreasing %FEV₁ predicted and current smoking in retired miners with COPD.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제44권4호
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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.

• Journal of Gastric Cancer
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• 제12권2호
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• pp.73-80
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• 2012

Purpose: The specific aim of this study is to unravel a DNA copy number alterations, and to search for novel genes that are associated with the development of Korean gastric cancer. Materials and Methods: We investigated a DNA copy number changes in 23 gastric adenocarcinomas by array-comparative genomic hybridization and quantitative real-time polymerase chain reaction analyses. Besides, the expression of UQCRFS1, which shows amplification in array-CGH, was examined in 186 gastric cancer tissues by an immunohistochemistry, and in 9 gastric cancer cell lines, as well as 24 gastric cancer tissues by immunoblotting. Results: We found common gains at 48 different loci, and a common loss at 19 different loci. Amplification of UQCRFS1 gene at 19q12 was found in 5 (21.7%) of the 23 gastric cancers in an array-comparative genomic hybridization and DNA copy number were increased in 5 (20.0%) out of the 25 gastric cancer in quantitative real-time polymerase chain reaction. In immunohistochemistry, the overexpression of the protein was detected in 105 (56.5%) out of the 186 gastric cancer tissues. Statistically, there was no significant relationship between the overexpression of UQCRFS1 and clinicopathologic parameters (P>0.05). In parallel, the overexpression of UQCRFS1 protein was confirmed in 6 (66.7%) of the 9 gastric cancer cell lines, and 12 (50.0%) of the 24 gastric cancer tissues by immunoblotting. Conclusions: These results suggest that the overexpression of UQCRFS1 gene may contribute to the development and/or progression of gastric cancer, and further supported that mitochondrial change may serve as a potential cancer biomarker.

• The Korean Journal of Physiology and Pharmacology
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• 제16권3호
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• pp.193-198
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• 2012

Changes in the expression profiles of specific proteins leads to serious human diseases, including colitis. The proteomic changes related to colitis and the differential expression between tuberculous (TC) and ulcerative colitis (UC) in colon tissue from colitis patients has not been defined. We therefore performed a proteomic analysis of human TC and UC mucosal tissue. Total protein was obtained from the colon mucosal tissue of normal, TC, and UC patients, and resolved by 2-dimensional electrophoresis (2-DE). The results were analyzed with PDQuest using silver staining. We used matrix-assisted laser desorption ionization time-of-flight/time-of-flight spectrometry (MALDI TOF/TOF) to identify proteins differentially expressed in TC and UC. Of the over 1,000 proteins isolated, three in TC tissue and two in UC tissue displayed altered expression when compared to normal tissue. Moreover, two proteins were differentially expressed in a comparative analysis between TC and UC. These were identified as mutant ${\beta}$-actin, ${\alpha}$-enolase and Charcot-Leyden crystal protein. In particular, the expression of ${\alpha}$-enolase was significantly greater in TC compared with normal tissue, but decreased in comparison to UC, implying that ${\alpha}$-enolase may represent a biomarker for differential diagnosis of TC and UC. This study therefore provides a valuable resource for the molecular and diagnostic analysis of human colitis.

• Mass Spectrometry Letters
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• 제5권3호
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• pp.63-69
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• 2014

In this study, we present a new isotope-coded carbamidomethylation (iCCM)-based quantitative proteomics, as a complementary strategy for conventional isotope labeling strategies, with providing the simplicity, ease of use, and robustness. In iCCM-based quantification, two proteome samples can be separately isotope-labeled by means of covalently reaction of all cysteinyl residues in proteins with iodoacetamide (IAA) and its isotope (IAA-$^{13}C_2$, $D_2$), denoted as CM and iCCM, respectively, leading to a mass shift of all cysteinyl residues to be + 4 Da. To evaluate iCCM-based isotope labeling in proteomic quantification, 6 protein standards (i.e., bovine serum albumin, serotransferrin, lysozyme, beta-lactoglobulin, beta-galactosidase, and alpha-lactalbumin) isotopically labeled with IAA and its isotope, mixed equally, and followed by proteolytic digestion. The resulting CM-/iCCM-labeled peptide mixtures were analyzed using a nLC-ESI-FT orbitrap-MS/MS. From our experimental results, we found that the efficiency of iCCM-based quantification is more superior to that of mTRAQ, as a conventional nonisobaric labeling method, in which both of a number of identified peptides from 6 protein standards and the less quantitative variations in the relative abundance ratios of heavy-/light-labeled corresponding peptide pairs. Finally, we applied the developed iCCM-based quantitative method to lung cancer serum proteome in order to evaluate the potential in biomarker discovery study.

• Safety and Health at Work
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• 제11권4호
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• pp.425-430
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• 2020

Background: Asbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM. Methods: This study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months. Results: Mean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p = 0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy. Conclusion: Monitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.

• Journal of Veterinary Science
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• 제22권5호
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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.

• Genomics & Informatics
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• 제20권3호
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• pp.26.1-26.19
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• 2022

Diabetes and its related complications are associated with long term damage and failure of various organ systems. The microvascular complications of diabetes considered in this study are diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. The aim is to identify the weighted co-expressed and differentially expressed genes (DEGs), major pathways, and their miRNA, transcription factors (TFs) and drugs interacting in all the three conditions. The primary goal is to identify vital DEGs in all the three conditions. The overlapped five genes (AKT1, NFKB1, MAPK3, PDPK1, and TNF) from the DEGs and the co-expressed genes were defined as key genes, which differentially expressed in all the three cases. Then the protein-protein interaction network and gene set linkage analysis (GSLA) of key genes was performed. GSLA, gene ontology, and pathway enrichment analysis of the key genes elucidates nine major pathways in diabetes. Subsequently, we constructed the miRNA-gene and transcription factor-gene regulatory network of the five gene of interest in the nine major pathways were studied. hsa-mir-34a-5p, a major miRNA that interacted with all the five genes. RELA, FOXO3, PDX1, and SREBF1 were the TFs interacting with the major five gene of interest. Finally, drug-gene interaction network elucidates five potential drugs to treat the genes of interest. This research reveals biomarker genes, miRNA, TFs, and therapeutic drugs in the key signaling pathways, which may help us, understand the processes of all three secondary microvascular problems and aid in disease detection and management.

• Journal of Gastric Cancer
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• 제23권2호
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• pp.340-354
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• 2023

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.