• BMB Reports
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• v.53 no.6
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• pp.311-316
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• 2020

Cholestasis is a condition in which the bile duct becomes narrowed or clogged by a variety of factors and bile acid is not released smoothly. Bile acid-induced liver injury is facilitated by necrotic cell death, neutrophil infiltration, and inflammation. Metformin, the first-line treatment for type 2 diabetes, is known to reduce not only blood glucose but also inflammatory responses. In this study, we investigated the effects of metformin on liver injury caused by cholestasis with bile acid-induced hepatocyte injury. Static bile acid-induced liver injury is thought to be related to endoplasmic reticulum (ER) stress, inflammatory response, and chemokine expression. Metformin treatment reduced liver injury caused by bile acid, and it suppressed ER stress, inflammation, chemokine expression, and neutrophil infiltration. Similar results were obtained in mouse primary hepatocytes exposed to bile acid. Hepatocytes treated with tauroursodeoxycholic acid, an ER stress inhibitor, showed inhibition of ER stress, as well as reduced levels of inflammation and cell death. These results suggest that metformin may protect against liver injury by suppressing ER stress and inflammation and reducing chemokine expression.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1440-1446
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• 1997

The radiologically detectable pulmonary involvement of NHL at diagnosis is about 4%. The commonest intrathoracic manifestations of secondary pulmonary lymphoma are mediastinal or hilar lymph node enlargement And the most frequent manifestations of pulmonary parenchymal lymphoma are lymphomatous nodules. But, when patients with newly diagnosed lymphoma exhibit rapidly progressive parenchymal lesions, an infection, such as pneumonia, is usually suspected. We present a report of a patient who developed rapidly progressive pulmonary involvement with T cell lymphoma, which was considered to be pneumonia because of high fever and rapidly progressive radiologic findings.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.79-85
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• 2020

Background: Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori-induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori-infected gastric epithelial cells. Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori-infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined. Results: H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori-infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori-infected gastric epithelial cells, similar to KRG. Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori-infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.

• Molecules and Cells
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• v.41 no.5
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• pp.401-412
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• 2018

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

• Environmental Mutagens and Carcinogens
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• v.25 no.4
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• pp.157-160
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• 2005

Antibiotic resistance of bacteria in the biofilm mode of growth contributes to the chronicity of infection and disease. The penetration of antibiotic, through biofilm developed in an itt vitro model system was investigated. Antibiotic resistant bacteria (E. coli) were obtained from Culture Collection of Antibiotic Resistant Microbes. Ca-alginate bead used as simulated biofilm and a cell entrapment test using compressed air were experiment for the improvement cell viability. Antibiotic susceptibilities though biofilms was measured by assaying the concentration of antibiotic that diffused through the biofilm to minimal inhibition concentration (MIC). Survival of immobilized cells were reduced as compared to free cells. In case of antibiotic susceptible E. coli reduced continuously, but antibiotic resistant E. coli kept up survival rate constantly. Survival was showed after exposed to the antibiotics that the more treated antibiotic resistant E. coli and low concentration of antibiotics) the more survived.

• Archives of Plastic Surgery
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• v.34 no.2
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• pp.261-264
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• 2007

Purpose: Extranodal marginal zone B cell lymphoma of MALT type represents approximately 8% of non-Hodgkin's lymphomas and this lymphoma is present in extranodal sites. Although the presentation of this lymphomain in stomach is usually associated with H. pylori infection in 95% of cases, MALT lymphoma found in soft tissue has been reported very rarely in the field of plastic surgery. We report a case of MALT lymphoma in the submandibular gland without any involvement of other organs such as the stomach. Methods: A 49-year-old man complained of a huge neck mass sized about $10{\times}12cm$. It started about 2 years ago and grew rapidly for the late 6 months. It was of hard nature with erythematous skin overlying it. Under the diagnosis of possible malignant lymphoma or sarcoma, radical resection was performed and the defect was reconstructed using transverse rectus abdominis musculocutaneous free flap. Results: The mass was well demarcated from the normal tissue, $11{\times}10.5{\times}10cm$ in size and whitish-gray color. Immunohistochemical analysis demonstrated that the tumor cells were LCA(+), CD20(+), CD3(-) and CD5(-). The tumor was diagnosed as extranodal marginal zone B cell lymphoma. The patient was treated with prophylactic radiation therapy after surgery, there was no complication for 1 year. Conclusion: We reported that very rare form of MALT lymphoma in 49-year-old male patient was experienced with clinical characteristics, histologic features and references.

• International Journal of Advanced Culture Technology
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• v.6 no.4
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• pp.275-283
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• 2018

Cancer show distinct pattern of gene expression when it is compared to normal. This difference results malignant characteristic of cancer. Many cancer drugs are targeting this difference so that it can selectively kill cancer cells. One of the recent demand for personalized treating cancer is retrieving normal tissue from a patient so that the gene expression difference between cancer and normal be assessed. However, in most clinical situation it is hard to retrieve normal tissue from a patient. This is because biopsy of normal tissues may cause damage to the organ function or a risk of infection or side effect what a patient to take. Thus, there is a challenge to estimate normal cell's gene expression where cancers are originated from without taking additional biopsy. In this paper, we propose in-silico based prediction of normal cell's gene expression from gene expression data of a tumor sample. We call this challenge as reverting the cancer into normal. We divided this challenge into two parts. The first part is making a generator that is able to fool a pretrained discriminator. Pretrained discriminator is from the training of public data (9,601 cancers, 7,240 normals) which shows 0.997 of accuracy to discriminate if a given gene expression pattern is cancer or normal. Deceiving this pretrained discriminator means our method is capable of generating very normal-like gene expression data. The second part of the challenge is to address whether generated normal is similar to true reverse form of the input cancer data. We used, cycle-consistent adversarial networks to approach our challenges, since this network is capable of translating one domain to the other while maintaining original domain's feature and at the same time adding the new domain's feature. We evaluated that, if we put cancer data into a cycle-consistent adversarial network, it could retain most of the information from the input (cancer) and at the same time change the data into normal. We also evaluated if this generated gene expression of normal tissue would be the biological reverse form of the gene expression of cancer used as an input.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2019.05a
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• pp.528-532
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• 2019

The dorsal root ganglion (DRG) was isolated from mouse embryos and Schwann cells and neuronal cells were cultured in vitro. The neurons and Schwann cells were cultured separately and the two kinds of cells were cultured together for three weeks. Generation of myelination was confirmed by transmission electron microscope and confocal microscope using a myelinaion protein, myelin protein zero (MPZ) antibody. The sindbis virus was infected for three days in the myelinated culture cells and then demyelination was carried out. The process of demyelination was also confirmed by transmission electron microscopy and confocal microscopy using myelin protein zero (MPZ) antibody. The study was supported by a Basic Research Program through the National Research Foundation (NRF) funded by the Ministry of Science and Technology, ICT and Future Plans (NRF-2016R1A2B4016552 and 2017R1A2B3005753).

• Journal of Ginseng Research
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• v.43 no.2
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• pp.312-318
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• 2019

Background: To date, no study has described disease progression in Asian patients infected with HIV-1 subtype D. Methods: To determine whether the disease progression differs in patients infected with subtypes D and B prior to starting combination antiretroviral therapy, the annual decline (AD) in $CD^{4+}$ T cell counts over $96{\pm}59months$ was retrospectively analyzed in 163 patients and compared in subtypes D and B based on the nef gene. Results: $CD^{4+}$ T cell AD was significantly higher in the six subtype D-infected patients than in the 157 subtype B-infected patients irrespective of Korean Red Ginseng (KRG) treatment (p < 0.001). Of these, two subtype D-infected patients and 116 subtype B-infected patients had taken KRG. AD was significantly lower in patient in the KRG-treated group than in those in the $KRG-na{\ddot{i}}ve$ group irrespective of subtype (p < 0.05). To control for the effect of KRG, patients not treated with KRG were analyzed, with AD found to be significantly greater in subtype D-infected patients than in subtype B-infected patients (p < 0.01). KRG treatment had a greater effect on AD in subtype D-infected patients than in subtype B-infected patients (4.5-fold vs. 1.6-fold). Mortality rates were significantly higher in both the 45 $KRG-na{\ddot{i}}ve$ (p < 0.001) and all 163 (p < 0.01) patients infected with subtype D than subtype B. Conclusion: Subtype D infection is associated with a >2-fold higher risk of death and a 2.9-fold greater rate of progression than subtype B, regardless of KRG treatment.

• Biomedical Science Letters
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• v.26 no.4
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• pp.288-295
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• 2020

Infection of Helicobacter pylori on gastric mucosa is associated with various gastric diseases. According to the WHO, H. pylori causes gastric cancer and has been classified as a class I carcinogen. Riboflavin is an essential vitamin which presents in a wide variety of foods. Previous studies have shown that riboflavin/UVA was effective against the growth inhibition of Staphylococcus aureus, S. epidermidis and multidrug-resistant Pseudomonas aeruginosa and had the potential for antimicrobial properties. Thus, we hypothesized that riboflavin has a potential role in the growth inhibition of H. pylori. To demonstrate inhibitory concentration of riboflavin against H. pylori, we performed agar and broth dilution methods. As a result, we found that riboflavin inhibited the growth of H. pylori. The MIC was 1 mM in agar and broth dilution test. Furthermore, to explain the inhibitory mechanism, we investigated whether riboflavin has an influence on the replication-associated molecules of the bacteria using RT-PCR to detect mRNA expression level in H. pylori. Riboflavin treatment of H. pylori led to down-regulation of polA and dnaB mRNA expression levels in a dose dependent manner. After then, we also confirmed whether riboflavin has cytotoxicity to human cells. We used AGS, a gastric cancer cell line, and treated with riboflavin did not show statistically significant decrease of cell viability. Thus, these results indicate that riboflavin can suppress the replication machinery of H. pylori. Taken together, these findings demonstrate that riboflavin inhibits growth of H. pylori by inhibiting replication of the bacteria.