• Journal of Cancer Prevention
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• v.21 no.2
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• pp.95-103
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• 2016

Background: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in $Apc^{Min/+}$ mice. Methods: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. Results: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2'-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). Conclusions: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis.

• 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.

• Clinical and Experimental Pediatrics
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• v.64 no.5
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• pp.229-238
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• 2021

Background: Bronchial hyperresponsiveness (BHR), an important physiological feature of asthma, is a prognostic marker of childhood asthma. Purpose: We aimed to investigate the factors associated with BHR in adolescents with childhood asthma. Methods: Two hundred and fifteen adolescents (≥13 years of age; 149 males, 66 females) who were diagnosed with asthma during childhood were enrolled, underwent methacholine challenge tests, and were divided into the BHR group (<25 mg/mL of provocation concentration causing a 20% fall in forced expiratory volume in 1 second [FEV₁] [PC₂₀], n=113) or non-BHR group (≥25 mg/mL of PC₂₀, n=102). We examined longitudinal changes in BHR and the risk factors for its persistence in the 108 adolescents for whom baseline data, including methacholine PC₂₀ at age 6 years, were available. Multivariate logistic regression analyses were performed to assess the factors associated with BHR in adolescents. Results: Mold sensitization (adjusted odds ratio [aOR], 5.569; P=0.005) and increased blood eosinophil count (aOR, 1.002; P=0.026) were independently associated with BHR in boys but not girls. The odds of BHR decreased by 32% with each 1-year increase in age in boys (aOR, 0.683; P=0.010) but not girls. A reduced FEV₁/forced vital capacity ratio (<90%) was independently related with BHR in female patients only (aOR, 7.500; P=0.007). BHR decreased with age throughout childhood. A low methacholine PC₂₀ at age 6 years was independently associated with persistent BHR throughout childhood in male and female patients, whereas early mold sensitization was a risk factor for persistent BHR in male patients only (aOR, 7.718; P=0.028). Conclusion: Our study revealed sex-specific differences in the factors associated with BHR in adolescents with childhood asthma. Our findings suggest the risk factors that might affect asthma transition from childhood to adolescence and adulthood.

• Molecules and Cells
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• v.44 no.9
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• pp.647-657
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• 2021

As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno-regulatory mechanism by which Reg3A modulates tumour-promoting responses during pancreatic cancer (PC) progression. In an in vitro Transwell system that allowed the direct co-culture of human peripheral blood-derived dendritic cells (DCs) and Reg3A-overexpressing/ silenced human PC cells, PC cell-derived Reg3A was found to downregulate CD80, CD83 and CD86 expression on educated DCs, increase DC endocytic function, inhibit DC-induced T lymphocyte proliferation, reduce IL-12p70 production, and enhance IL-23 production by DCs. The positive effect of tumour-derived Reg3A-educated human DCs on PC progression was demonstrated in vivo by intraperitoneally transferring them into PC-implanted severe combined immunodeficiency (SCID) mice reconstituted with human T cells. A Reg3A-JAK2/STAT3 positive feedback loop was identified in DCs educated with Reg3A. In conclusion, as a tumour-derived factor, Reg3A acted to block the differentiation and maturation of the most important antigen-presenting cells, DCs, causing them to limit their potential anti-tumour responses, thus facilitating PC escape and progression.

• Clinical and Experimental Pediatrics
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• v.62 no.3
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• pp.102-107
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• 2019

Purpose: This study compared the iron statuses of small for gestational age (SGA) and appropriate for gestational age (AGA) infants at birth. Methods: The clinical data of 904 newborn infants admitted to the neonatal intensive care unit were reviewed. Blood samples were drawn from the infants within 24 hours after birth. Serum ferritin level was used as a marker of total iron status. Results: In this study, 115 SGA (GA, $36.5{\pm}2.9weeks$; birth weight [BW], $1,975{\pm}594.5g$) and 717 AGA (GA, $35.1{\pm}3.5weeks$; BW, $2,420.3{\pm}768.7g$) infants were included. The SGA infants had higher hematocrit levels ($50.6%{\pm}5.8%$ vs. $47.7%{\pm}5.7%$, P<0.05) than the AGA infants. No difference in serum ferritin level (ng/mL) was found between the groups (mean [95% confidence interval]: SGA vs. AGA infants, 139.0 [70.0-237.0] vs. 141.0 [82.5-228.5]). After adjusting for gestational age, the SGA infants had lower ferritin levels (147.1 ng/mL [116.3-178.0 ng/mL] vs. 189.4 ng/mL [178.0-200.8 ng/mL], P<0.05). Total body iron stores were also lower in the SGA infants than in the AGA infants (185.6 [153.4-211.7] vs 202.2 [168.7-241.9], P<0.05). Conclusion: The SGA infants had lower ferritin and total body iron stores than the AGA infants. The SGA infants affected by maternal hypertension who were born at late preterm had an additional risk of inadequate iron store. Iron deficiency should be monitored in these infants during follow-up.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.5
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• pp.245-254
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• 2020

The purpose of this study was to investigate the effects of natural herb mixture containing Laminaria japonica Areschoung (LAM) on fine dust-induced bronchitis in mice. Laminaria japonica Areschoung is main content of LAM, which is including fucoidan. Fucoidan extracted from phaophyta is known to prevent bronchitis and to defend against bacteria and virus infection. In this study, we experienced the effect of LAM on bronchitis and investigated gene expressions (e.g ; IL-8, COX-2, MCP-1) and bio-markers (e.g ; IL-8, PGE2, MUC5AC) associated with bronchitis by using A549 cells. Also, we investigated whether LAM can suppress the bronchitis in fine dust-induced animal models. We injected fine dust (50 ㎕) twice as INT (Intra-Nasal-Trachea) method. Then LAM (200 mg/kg and 400 mg/kg) were oral administered for 14 days. We analyzed the number of immune cells, immunoglobulin E, bio-markers level associated with bronchitis. LAM significantly decreased bio-marker (IL-1β, IL-6, IL-8, TNF-α, Histamine, PGE2), immune cells (white blood cell, neutrophil, lymphocyte, monocyte), and immunoglobulin E, that are increased by fine dust. Taken together, this study suggest that LAM can be used as effective herbal extract for bronchitis.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.4
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• pp.270-284
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• 2021

The vomeronasal organ (VNO) is critical for reproduction and social behavior in ruminants, including cattle. The present study examined the structure of the VNO and its epithelial cells in neonatal and adult Korean native cattle (Hanwoo), Bos taurus coreanae, using immunohistochemistry and lectin histochemistry. Histologically, the VNO comprised two types of epithelia: medial vomeronasal sensory (VSE) and lateral vomeronasal non-sensory epithelia (VNSE). Numerous blood vessels and nerve bundles were observed within the vomeronasal cartilage encased lamina propria. Immunohistochemistry revealed high expression level of protein gene product9.5 and moderate expression level of olfactory marker protein in the neuroreceptor cells of the VSE and occasionally in some ciliated cells of the VNSE in both neonates and adults. The properties of the glycoconjugates in the VNO were investigated using 21 lectins, most of which were expressed at varied intensities in the VSE and VNSE, as well as in the lamina propria. Several lectins exhibited variations in their intensities and localization between neonatal and adult VNOs. This study is the first descriptive lectin histochemical examination of the VNO of Korean native cattle with a focus on lectin histochemistry, confirming that the VNO of Korean native cattle is differentiated during postnatal development.

• Tuberculosis and Respiratory Diseases
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• v.84 no.3
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• pp.188-199
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• 2021

Background: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with increased prevalence in the elderly. Telomeres are repetitive DNA sequences found at the end of the chromosome, which progressively shorten as cells divide. Telomere length is known to be a molecular marker of aging. This study aimed to assess the relationship between telomere length and the risk of COPD, lung function, respiratory symptoms, and emphysema index in Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) cohort. Methods: We extracted DNA from the peripheral blood samples of 446 participants, including 285 COPD patients and 161 control participants. We measured absolute telomere length using quantitative real-time polymerase chain reaction. All participants underwent spirometry and quantitative computed tomography scan. Questionnaires assessing respiratory symptoms and the COPD Assessment Test was filled by all the participants. Results: The mean age of participants at the baseline visit was 72.5±7.1 years. Males accounted for 72% (321 participants) of the all participants. The mean telomere length was lower in the COPD group compared to the non-COPD group (COPD, 16.81±13.90 kb; non-COPD, 21.97±14.43 kb). In COPD patients, 112 (75.7%) were distributed as tertile 1 (shortest), 91 (61.1%) as tertile 2 and 82 (55%) as tertile 3 (longest). We did not find significant associations between telomere length and lung function, exacerbation, airway wall thickness, and emphysema index after adjusting for sex, age, and smoking status. Conclusion: In this study, the relationship between various COPD phenotypes and telomere length was analyzed, but no significant statistical associations were shown.

• Nutrition Research and Practice
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• v.16 no.2
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• pp.147-160
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• 2022

BACKGROUND/OBJECTIVES: Patients with chronic kidney disease (CKD) have a high concentration of uremic toxins in their blood and often experience muscle atrophy. Indoxyl sulfate (IS) is a uremic toxin produced by tryptophan metabolism. Although an elevated IS level may induce muscle dysfunction, the effect of IS on physiological concentration has not been elucidated. Additionally, the effects of ursolic acid (UA) on muscle hypertrophy have been reported in healthy models; however, it is unclear whether UA ameliorates muscle dysfunction associated with chronic diseases, such as CKD. Thus, this study aimed to investigate whether UA can improve the IS-induced impairment of mitochondrial biogenesis. MATERIALS/METHODS: C2C12 cells were incubated with or without IS (0.1 mM) and UA (1 or 2 μM) to elucidate the physiological effect of UA on CKD-related mitochondrial dysfunction and its related mechanisms using real-time reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. RESULTS: IS suppressed the expression of differentiation marker genes without decreasing cell viability. IS decreased the mitochondrial DNA copy number and ATP levels by downregulating the genes pertaining to mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Sirt1, and Mef2c), fusion (Mfn1 and Mfn2), oxidative phosphorylation (Cycs and Atp5b), and fatty acid oxidation (Pdk4, Acadm, Cpt1b, and Cd36). Furthermore, IS increased the intracellular mRNA and secretory protein levels of interleukin (IL)-6. Finally, UA ameliorated the IS-induced impairment in C2C12 cells. CONCLUSIONS: Our results indicated that UA improves the IS-induced impairment of mitochondrial biogenesis by affecting differentiation, ATP levels, and IL-6 secretion in C2C12 cells. Therefore, UA could be a novel therapeutic agent for CKD-induced muscle dysfunction.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.3
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• pp.192-199
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• 2023

Objective: This study was conducted to investigate chromosomal abnormalities and their correlations with clinical and radiological findings in females with primary amenorrhea (PA). Methods: Detailed forms were recorded for 470 females, including the construction of three-generation pedigrees. Peripheral venous blood was drawn, with informed consent, for cytogenetic analysis. Results: An abnormal karyotype was found in 16.38% of participants. The incidence of structural abnormalities (6.8%) exceeded that of numerical abnormalities (6.15%). Turner syndrome represented 45% of all numerical abnormalities. Furthermore, the Y chromosome was detected in 5% of females with PA. Among the structural chromosomal abnormalities detected (n=32) were mosaicism (25%), deletions (12.5%), isochromosomes (18.75%), fragile sites (3.12%), derivatives (3.12%), marker chromosomes (3.12%), and normal variants (29.125%). An examination of secondary sexual characteristics revealed that 29.6% of females had a complete absence of breast development, 29.78% lacked pubic hair, and 36.88% exhibited no axillary hair development. Radiological findings revealed that 51.22% of females had a hypoplastic uterus and 26.66% had a completely absent uterus. Abnormal ovarian development, such as the complete absence of both ovaries, absence of one ovary, one absent and other streak, or both streak ovaries, was observed in 69.47% of females with PA. Additionally 43.1%, 36.1%, 67.4%, and 8% of females had elevated levels of serum follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and prolactin, respectively. Conclusion: This study underscores the importance of karyotyping as a fundamental diagnostic tool for assessing PA. The cytogenetic correlation with these profiles will aid in genetic counseling and further management of the condition.