• Journal of Veterinary Science
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• v.23 no.5
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• pp.74.1-74.16
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• 2022

Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

• Journal of Radiation Protection and Research
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• v.36 no.3
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• pp.119-126
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• 2011

Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and $H_2O_2$-treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and $H_2O_2$-treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-${\beta}$-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

• Nutrition Research and Practice
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• v.17 no.4
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• pp.660-669
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• 2023

BACKGROUND/OBJECTIVES: To investigate the effect and regulatory mechanism of resveratrol supplementation on the mitochondrial energy metabolism of rats with exercise-induced fatigue. MATERIALS/METHODS: Forty-eight Sprague-Dawley male rats were divided randomly into a blank control group (C), resveratrol group (R), exercise group (E), and exercise and resveratrol group (ER), with 12 rats in each group. Group ER and group E performed 6-wk swimming training with 5% wt-bearing, 60 min each time, 6 days a wk. Group ER was given resveratrol 50 mg/kg by gavage one hour after exercise; group R was only given resveratrol 50 mg/kg by gavage; group C and group E were fed normally. The same volume of solvent was given by gavage every day. RESULTS: Resveratrol supplementation could reduce the plasma blood urea nitrogen content, creatine kinase activity, and malondialdehyde content in the skeletal muscle, increase the total superoxide dismutase activity in the skeletal muscle, and improve the fatigue state. Resveratrol supplementation could improve the activities of Ca²⁺-Mg²⁺-ATPase, Na⁺-K⁺-ATPase, succinate dehydrogenase, and citrate synthase in the skeletal muscle. Furthermore, resveratrol supplementation could up-regulate the sirtuin 1 (SIRT1)-proliferator-activated receptor gamma coactivator-1α (PGC-1α)-nuclear respiratory factor 1 pathway. CONCLUSIONS: Resveratrol supplementation could promote mitochondrial biosynthesis via the SIRT1/PGC-1α pathway, increase the activity of the mitochondrial energy metabolism-related enzymes, improve the antioxidant capacity of the body, and promote recovery from exercise-induced fatigue.

• Tuberculosis and Respiratory Diseases
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• v.71 no.6
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• pp.425-430
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• 2011

Background: High 2-[$^{18}F$] fluoro-2-deoxy-D-glucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) is a prognostic factor for poor survival in non-small cell lung cancer (NSCLC), especially in Stage I. We determined whether the high FDG uptake value of a primary tumor was associated with recurrence and death in patients with resected Stage I and Stage II NSCLC. Methods: We identified consecutive patients who underwent complete surgical resection for Stage I and II NSCLC between 2006 and 2009, who had preoperative PET-CT, and reviewed clinical records retrospectively. FDG uptake was measured as the maximal standardized uptake value (SUVmax) for body weight. Patients were divided into two groups based on SUVmax: (i) above or (ii) below the cut-off value (SUVmax=5.9) determined by a receiver operating characteristic (ROC) curve. Results: Of 57 patients who were enrolled consecutively, 32 (56%) had Stage I NSCLC and 25 (44%) had Stage II. The 5-year recurrence-free survival (RFS) for patients with high (${\geq}5.9$) and low (<5.9) SUVmax were 31% and 57%, respectively (p=0.014). The 5-year overall survival (OS) rates were 39% and 60%, respectively (p=0.029). In univariate analyses, SUVmax (p=0.014), T staging (p=0.025), and differentiation of tumor tissue (p=0.034) were significantly associated with RFS. But, multivariate analyses did not show that SUVmax was an independently significant factor for RFS (p=0.180). Conclusion: High FDG uptake on PET-CT is not an independent prognostic factor for poor outcomes (disease recurrence in patients with resected Stage I and II NSCLC).

• The Korean Journal of Nuclear Medicine Technology
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• v.21 no.1
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• pp.65-69
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• 2017

Purpose KSNMT(Korea Society of Nuclear Medicine Technology) stepping first step in 1997, has published first journal related with nuclear medicine technology in 1985. With classifying In Vivo Session Dissertation reported in the entire journal, trend of the Dissertation will be studied. Materials and Methods Dissertations which published from 1985 to first half of 2016 in the journal are classified with presentation form and with scanner, And all the data is organized with Excel program. Through the data, the number of dissertations published in each year, the number of dissertation published in details, and keyword distributions in each period are analyzed. Results The number of In-vivo section dissertations was 1151 and the number of In-vivo section dissertations that have common subject with In-vitro section was 28. The number of In-vivo section dissertation in 1980s was 46, in 1990s was 149, in 2000 was 467 and from 2010 to the first half of 2016 was 517. The number of dissertation with original articles was 571, with abstract was 529, with symposium was 31, with special lecture was 25, with review was 11, with interesting image was 7, with poster was 3 and with case report was 2. With symposium and special lecture excluded, which count 56, the number of dissertation with PET was 319, with Planar was 302, with SPECT was 172, with radiopharmaceutical was 113, with guard and safety management 103, with BMD was 28, etc. was 86. The number of dissertation about oncology was 201, about scanner was 179, about cardiovascular and circulatory system was 102, about safe environment was 82, about musculoskeletal system was 76, about nervous nuclear medicine was 66, about quality assurance was 61, about genitourinary system was 56, about endocrine system was 49, about digestive system was 44, about Therapy, about industrial safety was 24, about molecular imaging was 15, infection and inflammation was 9, about respiratory system was 8 and etc. was 108. The mostly used keyword through 1999 to 2005 was PET and through 2006 to 2016 was PET/CT. Conclusion To encourage various dissertations to be submitted, Korea Society of Nuclear Medicine should analyze date about not only about dissertations that are already published, but also about various research materials. Moreover, Korea Society of Nuclear Medicine also have to provide technical support such as sharing big data from homepage and systematical support to its member to publish dissertation that has high impact factor. It is important each individual researcher to have continuing effort as well as each organization cooperation.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.133-142
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• 2019

Background: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells. Methods: Mouse AE II cell line MLE-12 were exposed to $1-10{\mu}g/mL$ BLM and $0.01-100{\mu}M$ baicalein (Bai), a G1/G2 cell cycle inhibitor, for 24 hours. Cell viability and levels of pro-inflammatory cytokines were analyzed by MTT and enzyme-linked immunosorbent assay, respectively. Apoptosis-related gene expression was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Cellular morphology was determined after DAPI and Hoechst 33258 staining. To verify cell cycle arrest, propidium iodide (PI) staining was performed for MLE-12 after exposure to BLM. Results: BLM decreased the proliferation of MLE-12 cells. However, it significantly increased expression levels of interleukin 6, tumor necrosis factor ${\alpha}$, and transforming growth factor ${\beta}1$. Based on Hoechst 33258 staining, BLM induced condensation of nuclear and fragmentation. Based on DAPI and PI staining, BLM significantly increased the size of nuclei and induced G2/M phase cell cycle arrest. Results of qRT-PCR analysis revealed that BLM increased mRNA levels of BAX but decreased those of Bcl2. In addition, BLM/Bai increased mRNA levels of p53, p21, SLFN1, 2, 4 of Schlafen family. Conclusion: BLM exposure affects pulmonary epithelial type II cells, resulting in decreased proliferation possibly through apoptotic and cell cycle arrest associated signaling.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.3
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• pp.324-330
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• 2015

In this study, the anti-diabetic activity of a cold water extract of Korean mistletoe (KME) was investigated in C57BL/6J Lep ob (ob/ob) mice. Oral administration of KME (50 or 100 mg/kg/d) significantly inhibited the level of blood glucose of ob/ob mice after 5 days from the beginning of KME treatment. And the anti-diabetic effect of KME was stabilized 10 days after oral administration, showing a substantial reduction of blood glucose levels by more than 20% as compared with control mice. The results of oral glucose tolerance test (OGTT) revealed that oral administration of KME gave rise to a remarkable improvement in overall glucose response. Oral administration of KME in ob/ob diabetic mice also significantly reduced blood total cholesterol (TCHO) and triglyceride (TG) levels compared with the diabetic control mice. Moreover, in an in vitro experiment using C2C12 myotubes, treatment of KME prominently increased glucose uptake. Interestingly, KME significantly increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}$ ($PGC-1{\alpha}$), a head regulator of mitochondrial biogenesis and oxidative metabolism, and $PGC-1{\alpha}$-associated genes such as glucose transporter type 4 (GLUT4), estrogen-related receptor-${\alpha}$ ($ERR-{\alpha}$), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TmfA) in C2C12 cells. These results suggest that KME has potential as a novel therapeutic agent for diabetes, and its anti-diabetic activity may be related to the regulation of mitochondrial biogenesis.

• Development and Reproduction
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• v.14 no.2
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• pp.75-82
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• 2010

The objective of this study is to identify the effects of endurance exercise and selenium on mitochondrial transcription factor in old Goto-Kakizaki (GK) rats. In this experiments, endurance exercise were treadmill-run at 24 m/min, 30 min/day, 5 days/week, 6 weeks and 5 umol/kg of sodium selenite was injected intraperitoneally. In exercise group, selenium group, and combination group, the mitohondrial biogenesis-related genes, including PGC-$1{\alpha}$, NRF-1, and Tfam expression level were significantly increased compared to control group. Consistent with the increased biogenesis-related genes, the cytochrome C in the treated groups, which was the indicator of mitochondrial content, was significantly increased compared to control group. Especially, combination of exercise and selenium may be effective in the increase of mitochondrial biogenesis, activity and insulin sensitivity. Therefore, exercise and selenium treatment is likely to promote diabeticmitochondrial malfunction and then improve diabetes.

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.22-31
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• 2012

Background: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. Methods: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and interleukin $1{\beta}$ (IL-$1{\beta}$) were measured in BALF. Nuclear factor ${\kappa}B$ (NF-${\kappa}B$), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. Results: TNF-${\alpha}$ and IL-$1{\beta}$ concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group ($5.5{\pm}2.8$ nmol/mL vs. $16.5{\pm}1.6$ nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group ($6.4{\pm}1.8$ unit/g vs. $11.2{\pm}6.3$ unit/g, tissue) (p<0.048). The concentration of NF-${\kappa}B$ in NAC treatment group was significantly lower than that of LPS group ($0.3{\pm}0.1\;ng/{\mu}L$ vs. $0.4{\pm}0.2\;ng/{\mu}L$) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. Conclusion: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-${\kappa}B$ activation.

• Tuberculosis and Respiratory Diseases
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• v.78 no.3
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• pp.218-226
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• 2015

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury. Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure). Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group ($4.30{\pm}2.93$ vs. $11.45{\pm}1.20$, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: $11.33{\times}10^4{\pm}8.84{\times}10^4$ vs. IgG+LPS: $208.0{\times}10^4{\pm}122.6{\times}10^4$; p=0.018) and total protein concentrations (EphA2 mAb+LPS: $0.52{\pm}0.41mg/mL$ vs. IgG+LPS: $1.38{\pm}1.08mg/mL$; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase $110{\gamma}$, phospho-Akt, nuclear factor ${\kappa}B$, and proinflammatory cytokines. Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.