• Journal of Life Science
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• v.29 no.11
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• pp.1179-1191
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• 2019

Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.

• Journal of Life Science
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• v.31 no.2
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• pp.229-236
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• 2021

This study was carried out to evaluate the antioxidant properties of the dried leaves and branches of Stewartia koreana Nakai. The dried leaf and branch of S. koreana were extracted with 70% ethanol at 80℃. The antioxidant activities of ethanol extracts of S. koreana leaf (EESL) and S. koreana branch (EESB) were analyzed. The total polyphenol contents in EESL and EESB were 162.57±0.9 mg of GAEs/extract g and 59.1±0.9 mg of GAEs/extract g, respectively. The flavonoid contents in EESL and EESB were 59.1±0.9 mg of QEs/extract g and 4.7±0.1 mg of QEs/extract g, respectively. EESL showed a better scavenging ability with DPPH and ABTS than EESB, at 0.4 mg/ml. Moreover, EESL were more effective according to ORAC values than EESL. The toxicity of EESL was investigated using a WST-1 assay on the human skin fibroblast cell line CCD-986sk. Therefore, EESL can be used as a potential source of functional, naturally-sourced material in cosmetics as well as food.

• Journal of Life Science
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• v.30 no.12
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• pp.1078-1084
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• 2020

Protaetia brevitarsis seulensis is an insect belonging to the order Coleoptera. This insect is reported to contain large amounts of physiologically active substances useful for liver protective effect and improvements in blood circulation as well as a broad source of edible protein. Antimicrobial peptides (AMPs) are found in a variety of species, from microorganisms to mammals, and play an important role in the innate immune systems of living things. Microglia are the main source of proinflammatory cytokines and nitric oxide (NO) in the central nervous system. Activated microglia secrete large amounts of neuroinflammatory mediators (e.g., TNF-α, NO, and ROS), which are the main cause of neuronal cell death. In the present study, we investigated the inhibitory effect of Protaetiamycine 6 (PKARKLQKLSAYKTTLRN-NH2), an AMP derived from Protaetia brevitarsis seulensis, on LPS-induced neuroinflammation in BV-2 microglia. Protaetiamycine 6 significantly inhibited NO production without cytotoxicity and decreased the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, Protaetiamycine 6 also reduced the production of neuroinflammatory cytokines on activated BV-2 microglia. These results suggest that Protaetiamycine 6 could be a good source of functional substance to prevent neuroinflammation and neurodegenerative diseases.

• Economic and Environmental Geology
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• v.54 no.3
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• pp.399-408
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• 2021

Natural soil was artificially contaminated with heavy metals (Cd, Pb, and Zn), and the movement of earthworm was characterized in real time using the ViSSET system composed of vibration sensor and the other components. The manifestation mechanism of ecological toxicity of heavy metals was interpreted based on the accumulative frequency of earthworm movement obtained from the real-time monitoring as well as the conventional indices of earthworm behavior, such as the change in body weight before and after tests and biocumulative concentrations of each contaminant. The results showed the difference in the earthworm movement according to the species of heavy metal contaminants. In the case of Cd, the earthworm movement was decreased with increasing its concentration and then tended to be increased. The activity of earthworm was severely increased with increasing Pb concentration, but the movement of earthworm was gradually decreased with increasing Zn concentration. The body weight of earthworm was proved to be greatly decreased in the Zn-contaminated soil, but it was similarly decreased in Cd- and Pb-contaminated soils. The bioaccumulation factor (BAF) was higher in the sequence of Cd > Zn > Pb, and particularly the biocumulative concentration of Pb did not show a clear tendency according to the Pb concentrations in soil. It was speculated that Cd is accumulated as a metallothionein-bound form in the interior of earthworm for a long time. In particular, Cd has a bad influence on the earthworm through the critical effect at its higher concentrations. Pb was likely to reveal its ecotoxicity via skin irritation or injury of sensory organs rather than ingestion pathway. The ecotoxicity of Zn seemed to be manifested by damaging the cell membranes of digestive organs or inordinately activating metabolism. Based on the results of real-time monitoring of earthworm movement, the half maximal effective concentration (EC50) of Pb was estimated to be 751.2 mg/kg, and it was similar to previously-reported ones. The study confirmed that if the conventional indices of earthworm behavior are combined with the results of newly-proposed method, the mechanism of toxicity manifestation of heavy metal contaminants in soils is more clearly interpreted.

• Korean Journal of Mineralogy and Petrology
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• v.35 no.4
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• pp.447-455
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• 2022

Fully dehydrated Tl₁₂-LTA (|Tl₁₂|[Si₁₂Al₁₂O₄₈]-LTA,Tl₁₂-A) was treated with 6.0×10³ Pa of ZrI₄ (g) at 623 K for 72 hr under anhydrous conditions. The crystal structure of product, |Zr_0.25I_1.5Tl₁₂|[Si₁₂Al₁₂O₄₈]-LTA, was determined by single-crystal crystallography using synchrotron X-radiation in the cubic space group Pm3m (a = 12.337(2) Å). It was refined using all data to the final error index (for the 712 unique reflections for which F_o> 4σ(F_o) R₁/wR₂= 0.055/0.189. In this structure, octahedral ZrI₆^2- ions center about 25% of the large cavities (Zr-I = 2.91(4) Å). Each coordinates to eight Tl⁺ ions and they are further bridged by Tl⁺ ions in the planes of 8-rings to form a cubic three-dimensional ZrI₆Tl₁₁⁹⁺ cationic cluster. About 1.5 Tl⁺ ions per unit cell moved to deeper side of sodalite cavity after reaction with ZrI₄(g). The remaining Tl⁺ ions occupy well-established cation positions near 6- and 8-rings.

• Journal of Life Science
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• v.32 no.12
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• pp.919-928
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• 2022

As seen in the COVID-19 pandemic, unexpected emergence of new viruses presents serious concern on public health. Especially, the absence of effective vaccines or antiviral drugs against emerging viruses significantly increases the severity of disease and duration of viral circulation among population. Natural products have served as a major source for safe and effective antiviral drugs. In this study, we examined the virucidal activity of medical herb extracts with a view to discover novel antiviral agents with desired levels of safety and antiviral efficacy. Ethanol extracts of ten selected medical herbs were tested for antioxidant activity and in-vitro cytotoxicity in various animal cell lines. Of note, the herbal extracts showed broad and potent virucidal activities against rotavirus, hepatitis A virus, and influenza A virus. The extracts of Sorbus commixta and Glycyrrhiza uralensis showed strong virucidal activities against influenza A virus. We also examined whether the extracts of Sorbus commixta and Glycyrrhiza uralensis can be used as inactivating agents to prepare an inactivated viral vaccine. In a mouse model, influenza A virus inactivated by the extracts elicited high levels of neutralizing antibodies, and the vaccination provided complete protection against lethal challenge. These results suggest that herb-derived natural products can be developed to antiviral drugs as well as inactivating agents for preparation of inactivated viral vaccines.

• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.106-112
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• 1999

The therapeutic potential of phosphodiesterase 4(PDE4) inhibitors in inflammatory diseases including some autoimmune diseases has been explored recently with some hopeful results. These PDE4 inhibitors are thought to show their anti-inflammatory effect by down-regulating tumor necrosis factor-a (TNF-$\alpha$) production in lymphocytes and macrophages. A high concentration of TNF-$\alpha$has been found in rheumatoid arthritis (RA) synovium and reducing TNF-$\alpha$using biological agents was proven to be an effective RA treatment. To test the possibility of using PDE4 inhibitors for RA treatment, the effects of a newly synthesized PDE4 inhibitor, DWP205505, on TNF-$\alpha$ and IL-10 production was tested in cells isolated from normal peripheral blood and rheumatoid arthritis synovial fluid. Cytokine production was assayed at the protein level by sandwich enzyme-linked immunosorbent assay (ELISA) and at the mRNA expression level by semi-quantitative RT-PCR. Another PDE4 inhibitor, RP73401, was used for comparison. DWP205505 and RP73401 had no harmful effect on cell viability up to 10 $\mu$M concentration during the 24 h culture period. DWP205505 as well as RP73401 significantly reduced TNF-$\alpha$ secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (pBMC) and synovial fluid mononuclear cells (SFMC). The effect of DWP205505 or RP73401 treatment on the mRNA expression of TNF-$\alpha$ was also studied in LPS-stimulated PBMC and SFMC. TNF-$\alpha$ mRNA expression was increased by LPS stimulation and both of the PDE4 inhibitors suppressed TNF-$\alpha$ mRNA expression. For interleukin-l0 (IL-l0), a little different results were obtained from PBMC and SFMC; IL-l0 secretion was unaffected by LPS stimulation and only minimally affected by both of the PDE4 inhibitors in PBMC. In unstimulated SFMC, DWP205505 and RP73401 slightly enhanced IL-10 secretion, while they reduced IL-l0 secretion from LPS-stimulated SFMC where IL-l0 secretion was a lot higher than unstimulated SFMC. These results suggest that the newly synthesized PDE4 inhibitor DWP205505 may have anti-rheumatoid arthritis activity.

• Journal of Life Science
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• v.34 no.5
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• pp.304-312
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• 2024

This study was conducted to characterize strain Y10, isolated from discarded chicken feathers. Strain Y10 was identified as Bacillus amyloliquefaciens through phenotypic and 16S rRNA gene analysis. B. amyloliquefaciens Y10 exhibited plant growth-promoting activities, including the production of fungal cell-degrading enzymes (cellulase, lipase, protease, and pectinase), siderophores, ammonia, and indoleacetic acid. Furthermore, strain Y10 was able to inhibit the mycelial growth of several phytopathogenic fungi. When 0.1% sucrose as a carbon source and 0.05% casein as a nitrogen source were added to the basal medium, adjusted to pH 10, and cultured at 35℃, the degradation rate of chicken feathers by strain Y10 was about two times higher than that of the basal medium, with the feathers almost completely degraded in four days. Strain Y10 also degraded various keratin substrates, including duck feathers, wool, and human nails. It was confirmed that the feather hydrolyzates prepared using strain Y10 exhibited antioxidant activities, such as 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (EC₅₀ = 0.38 mg/ml) and superoxide dismutase-like activity (EC₅₀ = 183.7 mg/ml). These results suggest that B. amyloliquefaciens Y10 is a potential candidate for the development of bioinoculants and feed additives applicable to the agricultural and livestock industries, as well as the microbiological treatment of keratin waste.

• Journal of Life Science
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• v.34 no.7
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• pp.443-452
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• 2024

This study aimed to examine the influence of 3,6-anhydroxygalactose (L-AHG) on the pro-inflammatory M1 polarization and pro-inflammatory responses observed in the RAW264.7 mouse macrophage cell line following stimulation with lipopolysaccharides (LPS). L-AHG exhibited a significant and dose-dependent inhibition of inducible nitric oxide synthase (iNOS) expression, a hallmark of M1 polarization, and subsequent NO production in LPS-stimulated RAW264.7 cells. Furthermore, the LPS-induced upregulation of cyclooxygenase-2 (COX-2), which drives the production of prostaglandin E2, an inflammatory mediator, was also inhibited by L-AHG. L-AHG did not affect the LPS-triggered Toll-like receptor 4 (TLR4)-mediated pro-inflammatory signaling pathway, which culminated in the activation of transforming growth factor-β-activated kinase 1 (TAK1). However, it was observed to inhibit the generation of reactive oxugen species (ROS) in a dose-dependent manner, as well as the TAK1-driven activation of JNK and p38 MAPK. Given that the active p38 MAPK is known to contribute to the assembly of active nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which catalyzes the intracellular generation of pro-inflammatory ROS in LPS-stimulated macrophages, the dose-dependent reduction in the LPS-induced ROS generation by L-AHG may be mainly due to the prevention of TAK1-driven activation of p38 MAPK. Together, these results demonstrate that the L-AHG-mediated inhibition of the TAK1-JNK/p38 MAPK activation phase of the pro-inflammatory signaling pathway in LPS-stimulated RAW264.7 cells by L-AHG represents a promising mechanism for suppressing M1 polarization and pro-inflammatory responses in macrophages.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.129-138
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• 2023

Purpose: Cancer incidence is known to be higher in patients with inborn errors of immunity (IEI) compared to the general population in addition to traditionally well-known infection susceptibility. We aimed to investigate cancer occurrence in patients with IEI in a single center. Methods: Medical records of IEI patients treated at Samsung Medical Center, Seoul, Korea were retrospectively reviewed from November 1994 to September 2023. Patients with IEI and cancer were identified. Results: Among 194 patients with IEI, seven patients (3.6%) were diagnosed with cancer. Five cases were lymphomas, 4 of which were Epstein-Barr virus (EBV)-associated lymphomas. The remaining cases included gastric cancer and multiple myeloma. The median age at cancer diagnosis was 18 years (range, 1-75 years). Among patients with cancer, underlying IEIs included X-linked lymphoproliferative disease-1 (XLP-1, n=3), activated phosphoinositide 3-kinase delta syndrome (APDS, n=2), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) haploinsufficiency (n=2). Seventy-five percent (3/4) of XLP-1 patients, 40.0% (2/5) of APDS patients, and 50.0% (2/4) of CTLA-4 haplo-insufficiency patients developed cancer. Patients with XLP-1 developed cancer at earlier age (median age 5 years) compared to those with APDS and CTLA-4 (P<0.001). One patient with APDS died during hematopoietic cell transplantation. Conclusions: Cancer occurred in 3.6% of IEI patients at a single center in Korea. In addition to infectious complications and inflammation, physicians caring for IEI patients should be aware of the potential risk of cancer, especially in association with EBV infection.