• Title/Summary/Keyword: liver cells

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Mesenchymal Stem Cell-derived Exosomes: Applications in Cell-free Therapy (중간엽줄기세포유래 엑소좀: 비세포치료제로서의 활용)

  • Heo, June Seok;Kim, Jinkwan
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.391-398
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    • 2018
  • Mesenchymal stem cells (MSCs) are an attractive resource for refractory patients because of their anti-inflammatory/immunomodulatory capability and multi-lineage differentiation potential. The transplantation of MSCs has led to positive results in preclinical and clinical application to various diseases, including autoimmune disease, cardiovascular disease, cancer, liver cirrhosis, and ischemic stroke. On the other hand, studies have shown that paracrine factors, not direct cell replacement for damaged cells or tissue, are the main contributors in MSC-based therapy. More recently, evidence has indicated that MSC-derived exosomes play crucial roles in regulating the paracrine factors that can mediate tissue regeneration via transferring nucleic acids, proteins, and lipids to the local microenvironment and cell-to-cell communication. The use of these exosomes is likely to be beneficial for the therapeutic application of MSCs because their use can avoid harmful effects, such as tumor formation involved in cell transplantation. Therefore, therapeutic applications using MSC-derived exosomes might be safe and efficient strategies for regenerative medicine and tissue engineering. This review summarizes the recent advances and provides a comprehensive understanding of the role of MSC-derived exosomes as a therapeutic agent.

Characteristics of Viral Endothelial Cell Necrosis of Eel (VECNE) from Culturing Eel (Anguilla japonica, Anguilla bicolar) in Korea (국내 양식산 뱀장어(Anguilla japonica, Anguilla bicolar)에서 발생하는 바이러스성내피세포괴사증(VECNE)의 감염 특성)

  • Kim, Su Mi;Ko, Sang Mu;Jin, Ji Hye;Seo, Jung Soo;Lee, Nam Sil;Kim, Young Suk;Gu, Jeong Hui;Bae, Yu Ri
    • Korean Journal of Ichthyology
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    • v.30 no.4
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    • pp.185-193
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    • 2018
  • From 2017 to 2018, the disease has been monitored at four culturing eel farms in Incheon and Gyeonggi region in Korea. As a result, diseases with gill congestion frequently occurred. This disease occurred regardless of size of eel, but the frequency and cumulative mortality were high in eels within 3 months after stocking. The infected fish showed pathological histopathological features such as intense congestion and dilation in the central venous sinus (CVS) of gill filaments and hemorrhages in liver and kidney. Hexagonal viral particles measuring about 70 nm in diameter was observed in nuclei and cytoplasm of gill vascular endothelial cells. Molecular biologic diagnosis by both PCR and genetic analysis has been revealed that the causative agent of this disease is Japanese eel endothelial cells-infecting virus (JEECV), the cause of viral endothelial cell necrosis of eel (VECNE), which is mainly reported in Japan. This study is the first report on the characteristics of JEECV and VECNE infection in domestic eel farms.

The Preventive Effect of Bacillus polyfermenticus KJS-2 and Bacillus mojavensis KJS-3 on Triton WR-1339-induced Hyperlipidemia (Triton WR-1339로 유도된 고지혈증에 대한 Bacillus polyfermenticus KJS-2와 Bacillus mojavensis KJS-3의 예방효과)

  • Lee, Jin Young;Lee, Seung Jae;Kim, Hyung Hoi;Kang, Jae Seon
    • Journal of Life Science
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    • v.31 no.3
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    • pp.346-355
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    • 2021
  • The purpose of this study was to evaluate the possibility that administration of Bacillus polyfermenticus KJS-2 (BP2), Bacillus mojavensis KJS-3 (Moja3), and their mixtures could control serum lipid levels. We observed changes in the blood cell level, metabolic function evaluation, and blood lipid levels after two weeks of oral administration of these microbial strains to hyperlipidemia-induced rats. Measurements of major cell changes in the white blood cells (WBC) indicated no significant effects due to the administration of the microbial strains. Platelet (PLT) levels decreased by 18.4% in the Triton WR-1339-treated group (NCON) and recovered to the control (CON) group levels in the positive control (PCON) group and the microbial strain-administered groups (p<0.05). No functional changes were observed in red blood cells (RBC) by Triton WR-1339-induced hyperlipidemia. The blood AST, ALT, BUN, and creatinine levels did not indicated effects on liver and kidney function, and all rats administered the microbial mixture recovered. The blood lipid levels in the microbe-treated groups indicated reduced levels of triglyceride (TG) and total cholesterol (TC), and increased levels of serum HDL cholesterol. The HMG-CoA inhibition rate of 7-O-succinyl macrolactin A (SMA) produced by BP2 showed similar activity at a concentration of 1,000 times lower than that achieved with atorvastatin. The administration of the microbial strains to the Triton WR-1339-induced rat model of hyperlipidemia resulted in reduced weight gain without affecting the food and water intake. Thus, blood circulation can be improved by controlling serum lipid levels by the combined administration of the BP2 and Moja3 microbial strains.

The Protective Effect of Zizania latifolia Extract against t-BHP-induced Oxidative Stress in HepG2 Cells (고장초 추출물의 t-BHP로 산화적 손상이 유도된 HepG2 세포 보호 효과)

  • Park, Se-Ho;Lee, Jae-Yeul;Yang, Seun-Ah;Bang, Daesuk;Jhee, Kwang-Hwan
    • Journal of Life Science
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    • v.31 no.3
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    • pp.338-345
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    • 2021
  • Zizania latifolia has long been used as a tea for both edible and medicinal purposes. However, research into the use of Z. latifolia as a high value-added edible material is lacking. In a previous study, we confirmed that tricin is the major component in Z. latifolia. In this study, we investigated the protective effect of a Z. latifolia extract (ZLE). Toxicity tests of ZLE or tricin on HepG2 cells revealed no toxicity due to ZLE or tricin at all concentrations used. The reduction in cell viability by tert-butyl hydroperoxide (t-BHP) was suppressed by treatment with ZLE or tricin. In addition, ZLE or tricin effectively inhibited the production of reactive oxygen species (generation of hydrogen peroxide, alkoxy free radicals, and peroxyl free radicals by t-BHP) and oxidative damage. ZLE or tricin treatments also increased the protein expression of superoxide dismutase 1 (SOD1), catalase, heme oxygenase-1 (HO-1), and nuclear factor erythroid-related factor 2 (Nrf2), which are known as antioxidant enzymes, suggesting that the protective effect of ZLE is related to activation of tricin. Taken together, the results indicate that Z. latifolia can be developed as a functional food material for improving liver function.

Effects of Changbudodam-tang on Obesity-induced Rats (창부도담탕이 비만 유도 흰쥐에 미치는 영향)

  • Kim, Soo-Hyeon;Lee, Eun-Kyu;Choe, Yoo-Jin;Jo, Seong-Hui;Yang, Seung-Jeong
    • The Journal of Korean Obstetrics and Gynecology
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    • v.34 no.1
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    • pp.48-65
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    • 2021
  • Objectives: This study was designed to evaluate the efficacy of Changbudodam-tang on obesity by using high-fat diet rats. Methods: Rats were divided into five groups. Normal group: Normal diet, Control group: High-fat diet, Positive control group: High-fat diet+Dietamin 4 mg/kg/day, Changbudodam-tang-Low group: High-fat diet+Changbudodam-tang 250 mg/kg/day, Changbudodam-tang-High group: High-fat diet+Changbudodam-tang 500 mg/kg/day. Weight, food intake were measured every week. After 7 weeks, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, Triglyceride, free fatty acid, aspartate aminotransferase, alanine aminotransferase, complete blood count were measured and messenger ribonucleic acid expression of adiponectin, peroxisome proliferator-activated receptor-γ, leptin were observed using Reverse transcription polymerase chain reaction of liver cells. Results: There was no difference in food intake between groups. Body weight tended to decrease compared with the Control group, but it wasn't statistically meaningfull. The total cholesterol, low density lipoprotein-cholesterol, Triglyceride, free fatty acid tended to decrease compared with the Control group. High density lipoprotein-cholesterol tended to decrease compared with the Control group, but it wasn't statistically meaningfull. White blood cell, red blood cell, hemoglobin, platelet, aspartate aminotransferase, alanine aminotransferase were not affected by Changbudodam-tang. The messenger ribonucleic acid expression of Adiponectin, peroxisome proliferator-activated receptor-γ, leptin, which are involved in the differentiation of adipocytes, was decreased compared with the Control group. Conclusions: Based on the results above, it is suggested that Changbudodam-tang can be applied to improving serum lipid levels in obese patients caused by high fat diets.

Hsa-miR-422a Originated from Short Interspersed Nuclear Element Increases ARID5B Expression by Collaborating with NF-E2

  • Kim, Woo Ryung;Park, Eun Gyung;Lee, Hee-Eun;Park, Sang-Je;Huh, Jae-Won;Kim, Jeong Nam;Kim, Heui-Soo
    • Molecules and Cells
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    • v.45 no.7
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    • pp.465-478
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    • 2022
  • MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate the expression of target messenger RNA (mRNA) complementary to the 3' untranslated region (UTR) at the post-transcriptional level. Hsa-miR-422a, which is commonly known as miRNA derived from transposable element (MDTE), was derived from short interspersed nuclear element (SINE). Through expression analysis, hsa-miR-422a was found to be highly expressed in both the small intestine and liver of crab-eating monkey. AT-Rich Interaction Domain 5 B (ARID5B) was selected as the target gene of hsa-miR-422a, which has two binding sites in both the exon and 3'UTR of ARID5B. To identify the interaction between hsa-miR-422a and ARID5B, a dual luciferase assay was conducted in HepG2 cell line. The luciferase activity of cells treated with the hsa-miR-422a mimic was upregulated and inversely downregulated when both the hsa-miR-422a mimic and inhibitor were administered. Nuclear factor erythroid-2 (NF-E2) was selected as the core transcription factor (TF) via feed forward loop analysis. The luciferase expression was downregulated when both the hsa-miR-422a mimic and siRNA of NF-E2 were treated, compared to the treatment of the hsa-miR-422a mimic alone. The present study suggests that hsa-miR-422a derived from SINE could bind to the exon region as well as the 3'UTR of ARID5B. Additionally, hsa-miR-422a was found to share binding sites in ARID5B with several TFs, including NF-E2. The hsa-miR-422a might thus interact with TF to regulate the expression of ARID5B, as demonstrated experimentally. Altogether, hsa-miR-422a acts as a super enhancer miRNA of ARID5B by collaborating with TF and NF-E2.

Antioxidative Activities and Protective Effects on Alcohol-Induced Oxidative Stress in the Human Hepatic HepG2 Cells of Undaria pinnatifida and Costaria costata Extracts (미역과 쇠미역 추출물의 항산화 및 간 보호 효과)

  • Kim, Ki An;Oh, Tae-Hwan;Chun, Sang-Ho
    • Journal of Marine Life Science
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    • v.6 no.2
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    • pp.66-72
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    • 2021
  • We investigated the antioxidant and hepatoprotective effects of extracts from the Undaria pinnatifida and Costaria costata against ethanol-induced oxidative damage. The total polyphenol and flavonoid contents were highest in the 70% ethanol extract from Undaria pinnatifida and Costaria costata. Also, the radical scavenging activity of DPPH (IC50 0.33± 0.21, 0.48±0.47 mg/ml) and ABTS (IC50 0.34±0.30, 0.47±0.17 mg/ml) in the 70% ethanol extract was higher than that of the hot water and 10% ethanol extracts. To determine the hepatoprotective effects of extracts in ethanol-induced oxidative damage, cell viability was measured using an MTT assay. In the pre-treatment of Undaria pinnatifida and Costaria costata hot water extracts, the concentration-dependent increased the cell viability compared with the ethanol treated cells (73.95%) by 89.91~97.63% and 84.99~90.54%, respectively. The data suggests that 70% ethanol extracts have antioxidant activity and hot water extracts exhibit hepatoprotective effects. Therefore, Undaria pinnatifida and Costaria costata may be considered potential agents for control ethanol-induced liver damage.

Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated Ca2+-activated Cl- channels

  • Ruilian Xiu;Jie Jia;Qing Zhang;Fengjiao Liu;Yaxin Jia;Yuanyuan Zhang;Beibei Song;Xiaodan Liu;Jingwei Chen;Dongyang Huang;Fan Zhang;Juanjuan Ma;Honglin Li;Xuan Zhang;Yunyun Geng
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.6
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    • pp.521-531
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    • 2023
  • Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (Emax) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

Monitoring of Japanese eel (Anguilla japonica) diseases from 2021 to 2023: significance of Japanese Eel Endothelial Cells-infecting Virus (JEECV) and Edwardsiella anguillarum (2021년부터 2023년까지 뱀장어(Anguilla japonica) 질병 모니터링: 혈관내피세포감염바이러스(JEECV)와 Edwardsiella anguillarum의 중요성)

  • Hyeon-Kyeong Kim;Mun-Hee Jang;Sung-Ju Jung
    • Journal of fish pathology
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    • v.36 no.2
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    • pp.239-250
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    • 2023
  • Disease monitoring was conducted to investigate the recent disease occurrence in Japanese eels (Anguilla japonica). Between May 2021 and March 2022, an investigation was conducted on eels from seven farms experiencing mortality. JEECV (Japanese eel endothelial cells-infecting virus) was detected in all examined farms, each exhibiting co-infections with 1 or 2 bacteria, including Edwardsiella anguillarum, E. piscisida, Aeromonas sp., Citrobacter freundii, Lactococcus garviae, or Vibrio sp. From March 2022 to October 2023, monthly periodic inspections were carried out at a farm in Yeonggwang, Jeollanam-do, for a total of 22 times. JEECV was detected in 10 out of 22 times, even when mortality was not recorded. Bacteria such as E. anguillarum, C. freundii, Aeromonas sp., and Vibrio sp. were isolated, but consistent clinical signs of liver abscess and hemorrhagic lesions were only recognized in fish infected with E. anguillarum. Other bacteria were often isolated from apparently healthy fish. In conclusion, mortality in eel farms frequently occurs due to co-infections of JEECV with bacteria rather than JEECV alone. Therefore, to reduce eel mortality, it is crucial to decrease co-infections, with a particular emphasis of JEECV and E. anguillarum.

Alterations and Co-Occurrence of C-MYC, N-MYC, and L-MYC Expression are Related to Clinical Outcomes in Various Cancers

  • Moonjung Lee;Jaekwon Seok;Subbroto Kumar Saha;Sungha Cho;Yeojin Jeong;Minchan Gil;Aram Kim;Ha Youn Shin;Hojae Bae;Jeong Tae Do;Young Bong Kim;Ssang-Goo Cho
    • International Journal of Stem Cells
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    • v.16 no.2
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    • pp.215-233
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    • 2023
  • Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.