• Journal of Life Science
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• v.31 no.6
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• pp.603-608
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• 2021

The purpose of this perspective research is to discuss the potential role of exercise-interventions in COVID-19, terms of prevention and prognosis in the periods of the COVID-19 vaccine. SARCO-CoV-2. COVID-19 was detected as a new virus causing severe cardiovascular and respiratory complications. It emerged as a global public health emergency and national pandemic. It caused more than 1 million deaths in the first 6 months of the pandemic and resulted in huge social and economic fluctuations internationally. Unprecedented stressful situations, such as COVID-19 blue and COVID-19 red impact on many health problems. In healthy individuals, COVID-19 infection may induced no symptoms (i.e., asymptomatic), whereas others may experience flu-like symptoms, such as ARDS, pneumonia, and death. Poor health status, such as obesity and cardiovascular and respiratory complications, are high risk factors for COVID-19 prevention, occurrence, and prognosis. Several COVID-19 vaccines are currently in human trials. However, the efficacy and safety of COVID-19 vaccines, including potential side effects, such as anaphylaxis (a life-threatening allergic reaction) and rare blood clots, still need to be investigated. On the basis of direct and indirect evidence, it seems that regular and moderate physical exercise can be recommended as a nonpharmacological, efficient, and safe way to cope with COVID-19. Physical inactivity and metabolic abnormalities are directly associated with reduced immune responses, including reduced innate, CMI, and AMI responses. Due to prolonged viral shedding, quarantine in inactive, obese and disease people should likely be longer than physical active people. Multicomponent and systemic exercise should be considered for the obese, disease, and elderly people. More mechanism research is needed in this area.

• Journal of Life Science
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• v.33 no.2
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• pp.169-175
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• 2023

As a protective defensive mechanism against ultraviolet (UV) light exposure in skin tissue, melanocytes produce the pigment melanin. Tyrosinase plays a key role in melanin production in melanocytes. However, the overproduction of melanin can lead to lesions, such as freckles and dark spots. Thus, it is clinically important to find a modulating molecule to control melanogenesis by regulating tyrosinase expression and/or activity. It is known that catechin, a plant flavonoid, can reduce melano- genesis through the downregulation of tyrosinase expression. Here, we tested whether catechin derivatives isolated from the stem bark of Ulmus parvifolia have an effect on melanin production by regulating tyrosinase in mouse melanoma cells and in vitro mushroom tyrosinase. The catechin derivatives used in this study included C5A, C7A, C7G, and C7X. Treatments using these catechin derivatives reduced melanin production in mouse melanoma B16F10 cells in which melanogenesis was stimulated by α-MSH. Notably, the anti-melanogenic effects of catechin derivatives were similar to those of kojic acid, a well-known anti-melanogenic molecule. Both C5A and C7A directly inhibited the activity of tyrosinase isolated from mushrooms in vitro. Furthermore, our in silico computational simulation showed that these two compounds were expected to bind to the active site of tyrosinase, which is similar to kojic acid. In addition, all four catechin derivatives reduced tyrosinase protein expression. In summary, our results showed that catechin derivatives can reduce melanogenesis by regulating tyrosinase activity or expression. Thus, this study suggests that catechin derivatives isolated from U. parvifolia can be novel modulators of melanin production.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.379-390
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• 1997

Background : It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pulmonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutropenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. Method : The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cells was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. Results : The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA : More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells : In the ETX-group, the number of total cells (p < 0.01) and of macrophage and neutrophil (p < 0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC-group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and it took part in less than 0.1% of total BAL cells (p < 0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF : In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p < 0.05 and < 0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p < 0.05 vs NC-group), but the value was statistically not different from that of ETX-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p < 0.05), but showed still a higher value compared to that of NC-group (p < 0.05). A change of cytokine concentration in the BALF : TNF -alpha and IL-6 were elevated in the ETX - and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells : There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p < 0.0008 vs NC-group), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion : Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveolar macrophages.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.51-66
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• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

• Korean Journal of Environmental Agriculture
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• v.22 no.3
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• pp.185-191
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• 2003

The mechanism imparting salt tolerance to crop plants remains still unsolved, although soybean has been classified as a susceptible plant to NaCl. To determine optimum parameters on physiological responses for improving sensitivity of salinity in breeding program, soybean (Glycine max Merr., cv. "Gwan-gan") plants were grown in a greenhouse, treated 20 days after emergence for 7 days with NaCl at 0, 30, 60, and 90mM, corresponding to electric conductivity of 1.2, 4.4, 7.3, and 10.4 dS/m, respectively, and assessed 30 days after treatment. Chlorophyll contents were significantly decreased by NaCl ($0.4{\sim}1.0\;mg/g$) compared to control (1.2 mg/g). Photosynthesis rate by NaCl treatment at $0{\sim}90\;mM$ at flowering stage was ranged from 5.0 (control) to $9.6\;{\mu}mol/m^2/s$. Oxygen for respiration was consumed from 5.4 to $9.7\;{\mu}mol/m^2/s$ so that the ratio of $O_2$ (evolution:consumption) was increased with the increase of NaCl, indicating that $O_2$ consumption seems to go beyond $O_2$ evolution. Water potential of leaf at vegetative stage II was ranged from -0.6 to -1.8 MPa and the highest level was observed at mid-day. Water potential by salt stress was decreased with range of $-2.1{\sim}-2.7MPa$ compared to control. Transpiration was decreased from 17% to 20% by NaCl stress. Water vapor diffusing resistance of intercellular air space was affected significantly, increasing up to $16{\sim}24%$ compared to control by NaCl treatment. Salt-treated soybean tended to accumulate $Na^+$, specially in root, with reduced absorption of N, P, $K^+$, $Ca^{2+}$, and $Mg^{2+}$ contents. Free proline content of soybean leaf as affected by different NaCl concentrations was increased 4.2 times ($184{\sim}434\;{\mu}g/g$) more than control. NaCl also increased activities of nitrate reductase and peroxidase by $28{\sim}161%$ and $3{\sim}22%$, respectively. The results show that physiological characteristics of soybean plants during assay were useful as the best parameters of salt stress or salt tolerance test to improve sensitivity in screening and breeding program among cultivars or germplasms.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.4
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• pp.403-412
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• 2016

The tight junction, one of Intercellular junctions, performs a variety of biological functions by bonding adjacent cells, including the barrier function to control the movement of the electrolyte and water. Recent studies have revealed that unusual expression of tight junction-related genes have been shown to be related in cancer development and progression. Recently, there are many reports that control of tight junction proteins expression is closely related to the skin moisture. In this study, we are focusing on the regulating mechanism of tight junction-associated genes by the steviol and its derivatives. Steviol, used as a sweetner, is known to chemical compound isolated from stevia plant. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay was carried out in HaCaT cells (human keratinocyte cell line) in order to determine the cytotoxicity. As a result, while steviol showing cytotoxicity from $250{\mu}M$, steviol derivatives are not cytotoxic more than $250{\mu}M$ concentration. We have observed a change in the tight junction protein via quantitative real-time PCR. Claudin 8 among tight junction proteins is only significantly reduced up to 30% in the presence of steviol. In addition, cell migration was inhibited by steviol, not by stevioside and rebaudioside. Finally, we could observe that steviol, not stevioside and rebaudioside, is able to increase the skin barrier permeability through the transepithelial electric resistance (TEER) measurements. These results suggest that the steviol and its derivatives are specifically acts on the tight junction related gene expression, but steviol derivatives are more suitable as a cosmetic material.

• Journal of Life Science
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• v.28 no.8
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• pp.945-954
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• 2018

Omega-3 polyunsaturated fatty acids (${\omega}3$-fatty acid) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effects in human tongue squamous cell carcinomas (SCCs) remain unclear. This study was designed to examine the effect of ${\omega}3$-fatty acid desaturase (fat-1) gene expression on invasion and tumorigenicity in human tongue SCC cells and the molecular mechanism of its action. Docosahexaenoic acid (DHA) treatment inhibited in vitro invasion in a dose-dependent manner. In zymography, matrix metalloproteinase-9 (MMP-9) and Matrix metallopeptidase-2 (MMP-2) activities were reduced, and MMP-9 and MMP-2 promoter activities were inhibited by the DHA treatment. In addition, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) promoter reporter activities were inhibited in SCC-4 and SCC-9 cells after the DHA treatment. To investigate the effect of a high level of endogenous ${\omega}3$ fatty acids, a stable SCC-9 cell line expressing the ${\omega}3$-desaturase gene (fSCC-9sc) was generated. The growth rate and colony-forming capacity of fSCC-9sc were remarkably decreased as compared with those of fSCC-9cc. Likewise, the tumor size and volume of fSCC-9sc implanted into nude mice were significantly inhibited, with increases in the cell death index. Furthermore, a transwell chamber invasion assay showed a reduction in cell invasion of the fSCC-9sc lines when compared with that of the fSCC-9cc line. These findings suggested that fat-1 gene expression inhibited tumorigenicity, as well as invasion in human tongue SCC cells. Thus, utilization of ${\omega}3$ fatty acids may represent a promising therapeutic approach for chemoprevention and the treatment of human tongue SCCs.

• Environmental Analysis Health and Toxicology
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• v.18 no.2
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• pp.89-94
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• 2003

Tributyltin (TBT) used world-wide in antifouling paints for ships is a widespread environmental pollutant and cause reproductive organs atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of toxicity in reproductive organs by TBT. In this study, we investigated that the mechanisms underlying DNA fragmentation induced by TBT in the rat leyding cell line, R2C. Effects of TBT on intracellular Ca$\^$2+/ level and reactive oxygen species (ROS) were investigated in R2C cells by fluorescence detector. TBT significantly induced intracellular Ca$\^$2+/ level in a time-dependent manner. The rise in intracellular Ca$\^$2+/ level was followed by a time-dependent generation of reactive oxygen species (ROS) at the cytosol level. Simultaneously, TBT induced the release of cytochrome c from the mitochondrial membrane into the cytosol. Furthermore, ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca$\^$2+/ chelator, indicating the important role of Ca$\^$2+/ in R2C during these early intracellular events. In addition, Z-DEVD FMK, a caspase-3 inhibitor, decreased apoptosis by TBT. Taken together, the present results indicated that the apoptotic pathway by TBT might start with an increase in intracellular Ca$\^$2+/ level, continues with release of ROS and cytochrome c from mitochondria, activation of caspases,and finally results in DNA fragmentation.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.1-11
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• 1989

In this study, it was aimed to investigate the role of serotonergic neurotransmission in nucleus tractus solitarius (NTS) for the central regulation of blood pressure and heart rate and its involvement in baroreceptor reflex activation in rats. A microinjection of 5-hydroxytryptamine (5-HT) into the NTS produced decreases in blood pressure and heart rate. Maximal decreases were $34.4{\pm}1.6$ mmHg and $41.7{\pm}10.2$ beats per min by 300 pmol of 5-HT. Microinjections of ${\alpha}-methylnor-adrenaline$ $({\alpha}-MNE)$ and clonidine manifested similar decreases in blood pressure and heart rate. The hypotensive and bradycardial effects of 5-HT were blocked by previous applications of 5-HT antagonists, ritanserin, methysergide and ketanserin into the NTS, respectively. By pretreatment with reserpine and 6-hydroxydopamine (6-OHDA, i.c.v.), both hypotensive and bradycardial effects of 5-HT were significantly attenuated. Pretreatment with 5, 7-dihydroxytryptamine (5,7-DHT, i.c.v.) enhanced the hypotensive and bradycardial effects of 5-HT. Similarly, following pretreatment with 6-OHDA, the effects of clonidine were increased. Pretreatment either with 5,7-DHT or 6-OHDA significantly attenuated the sensitivity of baroreflex produced either by phenylephrine or by sodium nitroprusside. When either 5,7-DHT or 6-OHDA was injected into the NTS $(5,7-DHT;\;8{\mu}g\;6-OHDA;\;10{\mu}g)$, both of the baroreflex sensitivities were impaired. In the immunohistochemical study, the injection of 6-OHDA into the the NTS led to reduction of axon terminal varicosity, however, the injection did not reduce the numbers of catecholaminergic cell bodies. Likewise, when 5,7-DHT was injected into the NTS, the varicosity of serotonergic axon terminals was markedly reduced. Based on these results, it is suggested that (1) stimulation of serotonergic receptors in the NTS leads to decreases in blood pressure and heart rate as observed with the stimulation of catecholaminergic system, (2) both serotonergic and catecholaminergic receptors may be located postsynaptically, and (3) the serotonergic neurons as well as catecholaminergic neurons may have a close relevance for the activation of baroreflex.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.346-352
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• 2010

Introduction: Heat shock protein70 (HSP70) is a highly conserved family of proteins produced after a variety of stresses. Many studies reported that the overexpression of HSP70 can improve the prognosis of the patients with sepsis through a reduction of the nitric oxide concentration. However, these results only revealed the effect of HSP70 and nitric oxide. No studies have examined the relationship between HSP70 and nitric oxide. The aim of this study was to evaluate the effect of the overexpression of HSP70 on the expression of inducible nitric oxide synthase and the nitric oxide concentration. In addition, the mechanism of the relationship of HSP70 and inducible nitric oxide synthase (iNOS) in sepsis was examined. Materials and Methods: The experiments were performed on male sprague-dawley rats. Sepsis was induced by a cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 hour after the initiation of sepsis. Serum and lung tissues were acquired from the rats 12 hours or 24 hours after the initiation of sepsis. The nitric oxide concentration, the expression of HSP70 in lung, and the gene expression of iNOS in lung were analyzed. The three groups, sham operation, CLP and CLP+GLN, were compared. Results: Compared to the other groups, in CLP+GLN, GLN administered after the initiation of sepsis enhanced the expression of HSP70 in the lung at 12 hours ($47.19{\pm}10.04$ vs. $33.22{\pm}8.28$, P=0.025) and 24 hours ($47.06{\pm}10.60$ vs. $31.90{\pm}4.83$, P=0.004). In CLP+GLN, GLN attenuated the expression of iNOS messenger RNA (mRNA) in the lung at 12 hours ($5,513.73{\pm}1,051.60$ vs. $4,167.17{\pm}951.59$, P=0.025) and 24 hours ($18,740.27{\pm}8,241.20$ vs. $9,437.65{\pm}2,521.07$, P=0.016), and reduced the concentration of nitric oxide in the serum at 12 hours ($0.86{\pm}0.48$ vs. $3.82{\pm}2.53$, P=0.016) and 24 hours ($0.39{\pm}0.25$ vs. $1.85{\pm}1.70$, P=0.025). Conclusion: The overexpression of HSP70 induced by the administration of GLN in sepsis attenuates the expression of the iNOS gene but reduces the nitric oxide concentration.