• Tuberculosis and Respiratory Diseases
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• 제84권3호
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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 Neurosurgical Society
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• 제64권3호
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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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• 제21권6호
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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.

• Molecules and Cells
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• 제45권9호
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• pp.640-648
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• 2022

CD133, also known as prominin-1, was first identified as a biomarker of mammalian cancer and neural stem cells. Previous studies have shown that the prominin-like (promL) gene, an orthologue of mammalian CD133 in Drosophila, plays a role in glucose and lipid metabolism, body growth, and longevity. Because locomotion is required for food sourcing and ultimately the regulation of metabolism, we examined the function of promL in Drosophila locomotion. Both promL mutants and pan-neuronal promL inhibition flies displayed reduced spontaneous locomotor activity. As dopamine is known to modulate locomotion, we also examined the effects of promL inhibition on the dopamine concentration and mRNA expression levels of tyrosine hydroxylase (TH) and DOPA decarboxylase (Ddc), the enzymes responsible for dopamine biosynthesis, in the heads of flies. Compared with those in control flies, the levels of dopamine and the mRNAs encoding TH and Ddc were lower in promL mutant and pan-neuronal promL inhibition flies. In addition, an immunostaining analysis revealed that, compared with control flies, promL mutant and pan-neuronal promL inhibition flies had lower levels of the TH protein in protocerebral anterior medial (PAM) neurons, a subset of dopaminergic neurons. Inhibition of promL in these PAM neurons reduced the locomotor activity of the flies. Overall, these findings indicate that promL expressed in PAM dopaminergic neurons regulates locomotion by controlling dopamine synthesis in Drosophila.

• 한국환경성돌연변이발암원학회지
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• 제23권2호
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• pp.56-62
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• 2003

The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.

• 대한한의학회지
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• 제44권3호
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• pp.10-28
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• 2023

Objectives: This study was designed to experiment with the antioxidant and anti-inflammatory effects of Taraxacum platycarpum H. Dahlstedt, Lonicera japonica Thunberg, and Leonurus japonicus Houtt. complex (TLL) in LPS-induced RAW264.7 cell. Methods: The antioxidant activity of TLL was measured by FRAP assay, DPPH radical scavenging activity, ABTS radical scavenging activity. Total polyphenol and flavonoid contents of TLL were measured by using standard methods. The anti-inflammatory effects of TLL were measured by NO production, biomarker production (PGE₂, IL-1β, IL-6, TNF-α), mRNA expression level (iNOS, COX-2, IL-1β, IL-6, TNF-α) and protein expression level (ERK, JNK, p38). Results: Total polyphenol and flavonoid contents in TLL were 58.03±1.02 mg of Gallic acid equivalents (GAE)/g and 16.58±0.60 mg of Quercetin equivalents (QE)/g respectively. In FRAP assay, DPPH and ABTS radical scavenging activity, a concentration-dependent increase in TLL was observed. To explore antioxidant and anti-inflammatory effects of TLL, RAW 264.7 cells were treated with TLL and LPS for 24 hours. Cell viability of RAW 264.7 cells were measured by adding EZ-Cytox, It was remarkably increased at 50, 100, 200 ㎍/㎖ concentrations of TLL. NO, ROS, iNOS, IL-1β, IL-6, TNF-α, ERK, JNK and p38 were remarkably decreased at 50, 100, 200 ㎍/㎖ concentrations of TLL compared to the control group. PGE₂ and COX-2 were remarkably decreased at 100, 200 ㎍/㎖ concentrations Conclusion: These results suggest that TLL complex has antioxidant and anti-inflammatory effects.

• Genomics & Informatics
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• 제21권4호
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• pp.46.1-46.10
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• 2023

Colon adenocarcinoma (COAD) is the predominant type of colorectal cancer. Early diagnosis and treatment can significantly improve the prognosis of COAD patients. Anoctamin 7 (ANO7), an anion channel protein, has been implicated in prostate cancer and other types of cancer. In this study, we analyzed the expression of ANO7 and its correlation with clinicopathological characteristics among COAD patients using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and the University of Alabama at Birmingham CANcer (UALCAN) databases. The GEPIA2, Kaplan-Meier plotter, and the Survival Genie platform were employed for survival analysis. The co-expression network and potential function of ANO7 in COAD were analyzed using GeneFriends, the Database for Annotation, Visualization and Integrated Discovery (DAVID), GeneMANIA, and Pathway Studio. Our data analysis revealed a significant reduction in ANO7 expression levels within COAD tissues compared to normal tissues. Additionally, ANO7 expression was found to be associated with race and histological subtype. The COAD patients exhibiting low ANO7 expression had lower survival rates compared to those with high ANO7 expression. The genes correlated with ANO7 were significantly enriched in proteolysis and mucin type O-glycan biosynthesis pathway. Furthermore, ANO7 demonstrated a direct interaction and a positive co-expression correlation with mucin 2 (MUC2). In conclusion, our findings suggest that ANO7 might serve as a potential prognostic biomarker and potentially plays a role in proteolysis and mucin biosynthesis in the context of COAD.

• IMMUNE NETWORK
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• 제23권4호
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• pp.34.1-34.15
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• 2023

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

• 대한한의학방제학회지
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• 제31권4호
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• pp.389-413
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• 2023

Objectives : This study aimed to review the current trends in experimental studies on the use of natural products for treatment of gastroesophageal reflux disease (GERD). Methods : Experimental studies assessing the efficacy of natural products against GERD were searched on PubMed. Articles were selected based on predefined inclusion and exclusion criteria and then analyzed for experimental methods, interventions, and result analysis techniques. Results : A total 37 studies were included in this review. Predominantly, in vivo experiments were conducted to induce GERD through surgery, involving the ligation of the pylorus and the transitional junction between the corpus and the forestomach using 7-week-old male Sprague-Dawley rats. The acute induction model, sacrificing animals after a single administration following GERD induction, was mainly used.The utilization of cell experiments was relatively infrequent, with a focus on assessing antioxidant and anti-inflammatory effects via the treatment of the RAW 264.7 cell line with lipopolysaccharides treatment. Glycyrrhizae Radix et Rhizoma, Pinelliae Tuber, Ginseng Radix and Zingiberis Rhizoma were used as single ingredients, and herbal formula, STW-5 (iberogast), Rikkunshito (六君子湯), Banhasasim-tang (半夏瀉心湯), and Hewei Jiangni granule (和胃降逆湯) were used. Outcome analysis methods encompassed Macroscopic evaluation, esophageal function assessment, blood biomarker analysis, histological examination, protein analysis, gene expression analysis, and gastric juice analysis. Proton pump inhibitors were predominantly employed as positive controls. Conclusions : This study revealed the current trends in non-clinical research evaluating natural products for GERD. Based on the results of this study, we expect that non-clinical research on clinically effective natural products will be revitalized.

• Journal of Korean Neurosurgical Society
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• 제67권3호
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• pp.364-375
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• 2024

Objective : Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. Methods : Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. Results : The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. Conclusion : Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.