• Journal of Life Science
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• v.33 no.10
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• pp.767-775
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• 2023

Sulfasalazine is a disease-modifying antirheumatic abiotic agent. It is a derivative of aminosalicylic acid and has been used for the treatment of various inflammatory diseases, such as rheumatoid arthritis, ulcerative colitis, and Crohn's disease, since it was first synthesized in 1941 and approved as a medicine in the United States in 1950. However, its mechanism of action has not yet been clearly identified. In this study, the effects of sulfasalazine on cell survival, apoptosis, and cell cycle progression in macrophages, which are major immune cells that regulate inflammatory responses, were investigated using mouse macrophage RAW 264.7 cells. Sulfasalazine inhibited the viability of RAW 264.7 cells in a dose-dependent manner, starting at a concentration of 0.25 mM. Annexin-V staining was used to confirm that the decrease in cell viability was due to apoptosis, and the number of Annexin-V-positive cells increased significantly at a concentration of 0.25 mM or higher. The effect of sulfasalazine on the expression of key proteins that regulate the G0/G1 phase of the cell cycle was also investigated. Sulfasalazine treatment significantly increased the expression of the cyclin-dependent kinase inhibitors p21 and p27 in RAW 264.7 cells. Although sulfasalazine is frequently used as a control drug in studies on inflammatory diseases, such as inflammatory colitis and rheumatoid arthritis, studies on its effect on macrophages are very limited. Therefore, the results of this study are expected to provide vital information on the use of sulfasalazine as a disease treatment.

• IMMUNE NETWORK
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• v.22 no.3
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• pp.22.1-22.25
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• 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

• Journal of Life Science
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• v.23 no.9
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• pp.1096-1103
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• 2013

Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.

• Journal of the East Asian Society of Dietary Life
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• v.24 no.2
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• pp.166-175
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• 2014

This study was conducted to investigate the hepatoprotective effects of fermented Smilax china leaf ethylacetate extracts by Aspergillus oryzae on carbon tetrachloride-induced liver injury in mice. Experimental mice were divided into four groups (five mice/group) (NC; normal control group, CB; basic diet supplemented before $CCl_4$ treatment group, NS ; basic diet mixed with 0.5% Smilax china leaf ethyl acetate extract supplemented before $CCl_4$ treatment group, FS; basic diet mixed with 0.5% fermented Smilax china leaf ethyl acetate extract supplemented before $CCl_4$ treatment group) fed for 4 weeks each. In the $CCl_4$-treated groups (CB, NS and FS) compared with the NC group, liver weights, activities of alanine aminotransferase, aspartate aminotransferase, xanthine oxidase and aldehyde oxidase, contents of triglycerides, total cholesterol and LDL-cholesterol in serum, and hepatic lipid peroxide levels increased, whereas body weight gain and contents of glutathione and HDL-cholesterol decreased. Furthermore, in the FS groups compared with the NS and CB groups, increased or decreased indicators by $CCl_4$ treatment significantly decreased or increased, respectively. This study suggests that fermented Smilax china L. leaf extracts may regulate xanthine oxidase and aldehyde oxidase inhibitory activities and hepatoprotective effects due to flavonoid aglycone derived from its glycoside in leaves of Smilax china by fermentation of A. oryzae.

• The Journal of the Convergence on Culture Technology
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• v.4 no.3
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• pp.197-207
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• 2018

The radish skin and radish greens (mucheong) are an edible part of the radish. But they are removed before eating the radish and used as a byproduct or an animal feed material because of their tough and rough texture. This study was conducted to investigate the effect of supercritical heat-treated radish-extract on UV-induced Hos: HRM-2 wrinkled mouse animal model on anti-aging wrinkles. Supercritical heat-treated radish-extract was applied on the back of seven-weeks old HRM-2 mice. The effect of HRE on skin thickness, elasticity and wrinkle formation of the mice was observed by using UVB lamp to induce melanogenesis and wrinkle formation. As the result, increased depth of wrinkles was observed in the negative control group in comparison to the normal group. In contrast, decreased depth of wrinkles was observed in the radish-extract-free group compared to the negative control group. In the study of the effect of radish-extract on wrinkle-formation related gene expression and protein what protein expression, MMP-2 and MMP-2 gene expression significantly increased in the negative control group compared to the normal group. The gene expression reduced independence to the mass of radish-extract treated. Similar to quantitative results of mRNA expression, the expression of MMP-2 protein increased as a result of UVB-irradiation. The MMP-2 expression was inhibited in dependence to the mass of radish-extract treated. In conclusion, the supercritical heat-treated radish-extract has an effect on improving skin wrinkles not only when it is applied to the skin but also when orally ingested. Thus, it can be effectively used as a composition to health functional products. Thereafter, we can also conclude that radish, a food that does not show any side-effects even upon long-term intake, can reduce wrinkle formation as well as improve skin elasticity when taken regularly for a long period.

• Journal of Applied Biological Chemistry
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• v.57 no.1
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• pp.53-59
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• 2014

To evaluate the inhibitory effect of xanthine oxidase (XO) and aldehyde oxidase (AO), and antihyperuricemic effect by Aspergillus oryzae fermented Smilax china L. leaf extracts and fractions, we observed extracted yield by each solvent, the content of total polyphenol and total flavonoid (TF), the activities of XO and AO, and serum uric acid level. Extracted yield (g/kg) by 80% ethanol (EtOH) was 13.56, those of n-hexane, dichloromethane (DICM), ethylacetate (EtOAc) and n-butanol fraction (BuOH) were 1.35-3.33. Furthermore, total polyphenol content (mg/g-extract) of EtOAc fraction, BuOH fraction, DICM fraction and EtOH fraction is 478.07-501.26, 259.49-289.02, 165.03-232.27, 134.02-196.54, respectively. Those of fermented EtOAc and DICM fraction was 4.85 and 40.74% higher than that of non-fermented fraction, respectively, while the other fermented fractions were lower than those of non-fermented fractions. And total flavonoid content (mg/g-extract) of EtOAc fraction was higher than those of other fractions. Additionally, TF of fermented EtOAc and BuOH fraction is 10.56 and 60.17% higher, than that of fermented fraction, respectively, although those of the other fermented fractions was lower than that of non-fermented fractions. On the other hand, XO inhibitory activities of all fermented fractions was significantly higher than that of all non-fermented fraction, while those of fermented EtOAc (75.02%) and BuOH fraction (65.59%) was markedly higher than that of non-fermented fraction (39.42 and 5.34%), respectively. In addition, AO inhibitory activities of DICM and EtOAc fraction was 81.82 and 77.93% higher, respectively, than those of the other fractions, and those of fermented fractions as with XO were significantly higher than that of non-fermented fractions. Meanwhile, serum uric acid level (SU) of hyperuricemic control mice (HC, 6.98 mg/dL) was 1.83 folds higher than that of normal control (NC, 3.82 mg/dL). Furthermore, SU in the group treated with EtOAc fraction decreased in a dose dependent manner compared with the allopurinol control group, although those of fermented fractions were significantly lower than those of non-fermented fractions. This study suggests that fermented Smilax china L. leaf extracts may regulate the XO and AO inhibitory activities and antihyperuricemic effect due to aglycone components from glycoside form flavonoids by fermentation of A. oryzae.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.4
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• pp.608-614
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• 2013

We investigated the anti-wrinkle activity of an 80% ethanol extract of Curdrania tricuspidata leaves (CTL80) on ultraviolet-induced photoaging in hairless mice. Skin wrinkles were induced by 10 weeks of UVB-irradiation on the back of Skh-1 hairless mice three times a week. Mice were divided into ten groups; normal control (-UVB), UVB irradiated control group (+UVB), dietary groups (UVB+ascorbic acid 0.1%, UVB+CTL80 0.1%, UVB+CTL80 0.25%) and topical application groups (-UVB+base lotion (BL), UVB+BL, UVB+ascorbic acid 1%+BL, UVB+CTL80 1%+BL, UVB+CTL80 2%+BL). Wrinkle formation, histological changes, superoxide dismutase (SOD) activities, glutathione peroxidase (GSH-Px), and the expression of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9) were analyzed. Wrinkles for the +UVB groups formed as a pattern of deep furrows and thick crests. Wrinkles with CTL80 treatment formed as a pattern of shallow furrows and thin crests, with wrinkle areas were lower than the +UVB group. In an antioxidant analysis of mouse blood, SOD and GSH-Px activities were significantly higher in the CTL80 topical application group compared to the +UVB group. The mRNA expression of MMPs in the +UVB group was significantly higher than the normal control group, and significantly lower in the CTL80-treated group. In conclusion, CTL80 exerted anti-wrinkle activity on ultraviolet-induced photoaging by regulating antioxidative defense systems and MMPs expression.

• Food Science and Preservation
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• v.22 no.6
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• pp.893-900
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• 2015

In this study, we evaluated the antidiabetic effect of a submerged culture of Ceriporia lacerata mycelium (CL01) on hematological indices, as well as protein and mRNA expression of the insulin-signaling pathway, in db/db mice. After CL01 was administrated for 4 weeks, blood glucose levels decreased consistently, and plasma insulin and c-peptide levels each decreased by roughly 55.8%, 40% of those in the negative control (p<0.05). With regard to HOMA-IR, an insulin resistance index, insulin resistance of the CL01-fed group improved over that of the negative control group by about 62% (p<0.05). In addition, we demonstrated that the protein expression levels of pIR, pAkt, pAMPK, and GLUT4 and the mRNA expression levels of Akt2, IRS1, and GLUT4 in the muscle cells of db/db mice increased in the CL01-fed group compared to the corresponding levels in the control group. These results demonstrate that CL01 affects glucose metabolism, upregulates protein and gene expression in the insulin-signaling pathway, and decreases blood glucose levels effectively by improving insulin sensitivity. More than 90% of those who suffer from type 2 diabetes are more likely to suffer from hyperinsulinemia, hypertension, obesity, and other comorbidities because of insulin resistance. Therefore, it is possible that CL01 intake could be used as a fundamental treatment for type 2 diabetes by lowering insulin resistance, and these results may prove be useful as basic evidence for further research into the mechanisms of a cure for type 2 diabetes.

• Korean Journal of Animal Reproduction
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• v.24 no.3
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• pp.231-239
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• 2000

In this study, we observed the effects of dioxin on weights of body, testes and other organs, the number and motility of sperm in the a various dose after two days' of administration in mice. Animals were treated with oral dose of dioxin 10, 20, 30, 40 mg/kg body weight, respectively. 1, After administration dioxin at doses of 10, 20, 30 and 40 $\mu\textrm{g}$/kg to the mice, the changes in body weights were 30.6 $\pm$ 2.g~40.7 $\pm$ 3.9g and 30.8 $\pm$4.1g~39.5g $\pm$3.1 for 10 and 20 $\mu\textrm{g}$/kg dosed group, 31.0 $\pm$ 3.5g ~ 39.0 $\pm$ 3.5g, 30.6 $\pm$ 3.4g~38.3 $\pm$ 4.0g for 30 and 40 $\mu\textrm{g}$/kg dosed group. The body weight of dioxin-administered group showed lower value when compared to 30.6 $\pm$ 2.8g ~ 44.5 $\pm$ 3.1g of which is control group's. 2. After administration of dioxin at doses of 10, 20, 30 and 40 $\mu\textrm{g}$/kg to the mice, the increase in the number of WBC was prominent, but the increase in the number of RBC wasn't significant, though the values of Hb, PCV, and PLT were higher than those of control group's. 3. After administration of dioxin at doses of 10. 20, 30 and 40 $\mu\textrm{g}$/kg to the mice, the changes in sperm number were 112.5 $\pm$ 3.7~119.4 $\pm$4.2 $\times$ 10$^{6}$ $m\ell$, 103.9 $\pm$3.8 ~ 110.2 $\pm$ 3.6 $\times$ 10$^{6}$ $m\ell$, 97.5 $\pm$ 3.4 ~105.7 $\pm$ 4.4 $\times$ 10$^{6}$ $m\ell$, 87.2 $\pm$ 3.7~98.5 $\pm$ 3.8 $\times$ 10$^{6}$ $m\ell$, respectively. The sperm number of dioxin-administered group showed lower value than that of control group's, which was 119.0 $\pm$ 4.3 ~ 120.7 $\pm$ 4.8 $\times$ 10$^{6}$ $m\ell$. After administration of dioxin at doses of 10~40 $\mu\textrm{g}$/kg to the mice, the sperm motility were 69.4$\pm$ 3.0 ~ 86.6 $\pm$4.7%. The sperm motility of dioxin-administered group showed lower value than that of control group's. 4. After administration of dioxin at doses of 10, 20, 30 and 40$\mu\textrm{g}$/kg to the mice, the organ weight of each dioxin-administered group's was decreased a little compared to that of control group's. 5. After administration of dioxin at doses of 10, 20, 30 and 40 $\mu\textrm{g}$/kg to the mice, the weights of spleen, kidneys, and liver showed increase a little.

• Parasites, Hosts and Diseases
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• v.29 no.3
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• pp.279-292
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• 1991

The immune response to sheep red blood cell (sRBC) was monitored in the mice infected with Ascaris strum or Trichinella spiralis. The effects of the infection with T. spiralis or the injection with cyclophosphamide (CY) as an immunosuppression agent prior to challenge infection with the embryonated eggs of A. suum were monitored in mice by means of the level of infection with A. strum and cellular and humoral immune response to sRBC. following the oral administration of 1, 000 eggs of A. suum to mice, delayed-type hypersensitivity (DTH) and rosette-forming rate were gradually decreased and reached to the lowest levels at the 5th week and 6th week postinfection, respectively, and then returned to normal at the loth week. The hemagglutinin (HA) and hemolysin (HE) titers were gradually elevated and reached to peak at the 3rd week postinfection, and then returned to normal level. The appearance ratios of the eosinophils and mast cells were in peak at the 4th week and the 2nd week postinfection, respectively. Meanwhile the harvest ratio of A. suum larvae from the liver and lungs was 21.97% at the 1st week postinfection. Following the oral administration of 300 T. spiralis infective larvae, DTH and rosette-forming rate were gradually decreased with the lapse of time and reached the lowest values in the 30th and 21st day of postinfection, and then slightly increased and transiently decreased in the 70th and 80th day of postinfection, respectively. HA and HE titers were the lowest in the 21st and 90th day, whereas the ratios of eosinophils and mast cells were the highest on the 40th and 14th day posti nfecti on, ruts petit i vela. Following the intraperitoneal injection of CY, the body weight, the spleen weight, DTH, rosette-orming ratio, HA and HE titers, the number of WBC and the ratio of the mast cell were predominantly decreased in the 5th day, and then returned to the same value of the 1st day postinjection. The ratio of eosinophils was gradually decreased following to advance of days. At the 1st, 5th and loth days after intraperitoneal injection of CY of 400 mg/kg, a dose with 1, 000 eggs of A. suum was administered orally to mice, and harvest rate of the larvae at the 7th day postadministration was 7.07% in the 1st day, 14.94% in the 5th day, 10.1% in the loth day, 8.02% in control group. The effect of prior infection with infective larvae of T. spiralis upon immunological sequelae of a challenge infection of mice with embryonated eggs of A. suum in 30 or 70 days interval was checked. On the 37th day of prior infection with T. spiralis, that was the 7th day with A. suum postinfection, DTH and rosette-forming rate were drastically decreased, but the ratio of mast cells was highly increased and the ratio of eosinophils, HA and HE titers were fairly increased. On the other hand, the rate of larvae harvest was 9.3% in experimental group in contrast with 22.18% in control group. Meanwhile the effect of immune response to sRBC was similar to that of the former, but DTH and rosettt-forming rate were greatly decreased in the 77th day after prior infection with the 7th day after challenge infection in compariton with control. At that time, Ascaris larvae were harvested 8.3% in experimental group in comparison with 10.5% in control group.