• YAKHAK HOEJI
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• v.57 no.1
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• pp.37-42
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• 2013

In this present study, we determined the immunoregulatory activity of ginsenoside Rd extract from Panax ginseng. To determine the activity, we tested Rd against $CD4^+$ Th cells in a murine model of type 1 diabetes, which involves Th1-dominant immunity. The type 1 diabetes was caused by streptozotocin (STZ) and the severity of the diabetes was evaluated by measuring the degree of hyperglycemia, a major symptom of diabetes. The data resulting from experiments showed that ginsenoside Rd induced a greater level of Th1 type cytokines [IFN-${\gamma}$ & IL-2] than Th2 type [IL-4 & IL-10] (P<0.05), which was determined by cytokine profile analysis. In the animal model of diabetes, the depletion of $CD4^+$ Th cells by a treatment of anti-CD4 mAb resulted in considerably lower values of blood-glucose levels than those of the mAb-untreated mice, which indicates that the Th1 immune response from $CD4^+$ Th cells are responsible for diabetes. Based on these observations, the effect of Rd on diabetes was examined in the same animal model. Results showed that Rd-treated mice groups had increased levels of blood glucose compared to Rd-untreated mice groups that were used as a negative control (P<0.05). In other words, Rd aggravated the diabetes via the Th1 immune response. In conclusion, ginsenoside Rd had an immunoregulatory activity of Th1-dominant immunity.

• Molecules and Cells
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• v.42 no.11
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• pp.773-782
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• 2019

Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKT-mTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53-dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, $p21^{Cip1/WAF1}$ is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of $p21^{Cip1/WAF}$. Taken together, these results suggest that CK2 downregulation induces dephosphorylation of Ser 392 on p53, which subsequently increases the stability of SUV39h1 and the expression of $p21^{Cip1/WAF1}$, leading to H3K9me3 and SAHFs formation.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.225-236
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• 2021

The epipyrone (EPN) biosynthetic gene cluster of Epicoccum nigrum is composed of epnC, epnB, and epnA, which encode cytochrome P450 oxidase, glycosyltransferase, and highly reducing polyketide synthase, respectively. Gene inactivation mutants for epnA, epnB, and epnC were previously generated, and it was found that all of them were incapable of producing EPN and any of its related compounds. It was also reported that epnB inactivation abolished epnA transcription, generating ΔepnAB. This study shows that the introduction of native epnC readily restored EPN production in ΔepnC, suggesting that epnC is essential for polyketide release from EpnA and implies that EpnC works during the polyketide chain assembly of EpnA. Introduction of epnC promoter-epnA restored EPN production in ΔepnA. The ΔepnB genotype was prepared by introducing the epnA expression vector into ΔepnAB, and it was found that the resulting recombinant strain did not produce any EPN-related compounds. A canonical epnB inactivation strain was also generated by deleting its 5'-end. At the deletion point, an Aspergllus nidulans gpdA promoter was inserted to ensure the transcription of epnA, which is located downstream of epnB. Examination of the metabolite profile of the resulting ΔepnB mutant via LC-mass spectrometry verified that no EPN-related compound was produced in this strain. This substantiates that C-glycosylation by EpnB is a prerequisite for the release of EpnA-tethered product. In conclusion, it is proposed that cytochrome P450 oxidase and glycosyltransferase work in concert with polyketide synthase to generate EPN without the occurrence of any free intermediates.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.177-187
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• 2021

Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

• Microbiology and Biotechnology Letters
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• v.47 no.2
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• pp.310-316
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• 2019

Distribution of Salmonella enterica serovars and their associated virulence determinants is wide-spread among food animals, which are continuously implicated in periodic salmonellosis outbreaks globally. The aim of this study was to determine and evaluate the diversity of five Salmonella serovar virulence genes (invA, pefA, cdtB, spvC and iroN) isolated from food animals and humans. Using standard microbiological techniques, Salmonella spp. were isolated from the feces of humans and three major food animals. Virulence determinants of the isolates were assayed using PCR. Clonal relatedness of the dominant serovar was determined via pulsed-field gel electrophoresis (PFGE) using the restriction enzyme, Xbal. Seventy one Salmonella spp. were isolated and serotyped into 44 serovars. Non-typhoidal Salmonella (NTS; 68) accounted for majority (95.8%) of the Salmonella serovars. Isolates from chicken (34) accounted for 47.9% of all isolates, out of which S. Budapest (14) was predominant (34.8%). However, the dominant S. Budapest serovars showed no genetic relatedness. The invA gene located on SPI-1 was detected in all isolates. Furthermore, 94% of the isolates from sheep harbored the spvC genes. The iroN gene was present in 50%, 100%, 88%, and 91% of isolates from human, chicken, sheep, and cattle, respectively. The pefA gene was detected in 18 isolates from chicken and a single isolate from sheep. Notably, having diverse Salmonella serovars containing plasmid encoded virulence genes circulating the food chain is of public health significance; hence, surveillance is required.

• Molecules and Cells
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• v.42 no.10
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• pp.702-710
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• 2019

Neuroinflammation is an important contributor to the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD). We previously reported that our novel synthetic compound KMS99220 has a good pharmacokinetic profile, enters the brain, exerts neuroprotective effect, and inhibits $NF{\kappa}B$ activation. To further assess the utility of KMS99220 as a potential therapeutic agent for PD, we tested whether KMS99220 exerts an anti-inflammatory effect in vivo and examined the molecular mechanism mediating this phenomenon. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, oral administration of KMS99220 attenuated microglial activation and decreased the levels of inducible nitric oxide synthase and interleukin 1 beta ($IL-1{\beta}$) in the nigrostriatal system. In lipopolysaccharide (LPS)-challenged BV-2 microglial cells, KMS99220 suppressed the production and expression of $IL-1{\beta}$. In the activated microglia, KMS99220 reduced the phosphorylation of $I{\kappa}B$ kinase, c-Jun N-terminal kinase, and p38 MAP kinase; this effect was mediated by heme oxygenase-1 (HO-1), as both gene silencing and pharmacological inhibition of HO-1 abolished the effect of KMS99220. KMS99220 induced nuclear translocation of the transcription factor Nrf2 and expression of the Nrf2 target genes including HO-1. Together with our earlier findings, our current results show that KMS99220 may be a potential therapeutic agent for neuroinflammation-related neurodegenerative diseases such as PD.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1927-1936
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• 2020

Tunicates are known to contain biologically active materials and one species in particular, the sea peach (Halocynthia aurantium), has not been thoroughly studied. In this study we aimed to analyze the fatty acids profile of the H. aurantium body wall and its immunomodulatory effects on RAW264.7 macrophage-like cells. The fatty acids were classified into three categories: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). Omega-3 fatty acid content, including EPA and DHA, was higher than omega-6 fatty acids. H. aurantium body wall fatty acids exhibited enhanced immune response and anti-inflammatory effects on RAW264.7 macrophage-like cells. Under normal conditions, fatty acids significantly increase nitric oxide (NO) and PGE2 production in a dose-dependent manner, thereby improving the immune response. On the other hand, in LPS-treated RAW264.7 cells, fatty acids significantly decreased nitric oxide (NO) and PGE2 production in a dose-dependent manner, thereby enhancing anti-inflammatory effects. Fatty acids transcriptionally control the expression of the immune-associated genes, iNOS, IL-1β, IL-6, COX-2, and TNF-α, via the MAPK and NF-κB signaling cascades in RAW264.7 cells. However, in LPS-stimulated RAW264.7 cells, H. aurantium body wall fatty acids significantly inhibited expression of inflammatory cytokine; similarly, production of COX-2 and PGE2 was inhibited. The results of our present study provide insight into the immune-improving and anti-inflammatory effects of H. aurantium body wall fatty acids on macrophages. In addition, our study demonstrates that H. aurantium body wall is a potential source of immune regulatory components.

• Steel and Composite Structures
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• v.38 no.5
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• pp.477-496
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• 2021

The main objective of this paper is to study vibration of sandwich open cylindrical panel with damaged core and FG face sheets based on three-dimensional theory of elasticity. The structures are made of a damaged isotropic core and two external face sheets. These skins are strengthened at the nanoscale level by randomly oriented Carbon nanotubes (CNTs) and are reinforced at the microscale stage by oriented straight fibers. These reinforcing phases are included in a polymer matrix and a three-phase approach based on the Eshelby-Mori-Tanaka scheme and on the Halpin-Tsai approach, which is developed to compute the overall mechanical properties of the composite material. Three complicated equations of motion for the panel under consideration are semi-analytically solved by using 2-D differential quadrature method. Several parametric analyses are carried out to investigate the mechanical behavior of these multi-layered structures depending on the damage features, through-the-thickness distribution and boundary conditions. It is seen that for the large amount of power-law index "P", increasing this parameter does not have significant effect on the non-dimensional natural frequency parameters of the FG sandwich curved panel. Results indicate that by increasing the value of isotropic damage parameter "D" up to the unity (fully damaged core) the frequency would tend to become zero. One can dictate the fiber variation profile through the radial direction of the sandwich panel via the amount of "P", "b" and "c" parameters. It should be noticed that with increase of volume fraction of fibers, the frequency parameter of the panels does not increase necessarily, so by considering suitable amounts of power-law index "P" and the parameters "b" and "c", one can get dynamic characteristics similar or better than the isotropic limit case for laminated FG curved panels.

• Animal Bioscience
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• v.35 no.7
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• pp.1080-1090
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• 2022

Objective: This study aimed to characterize the effect of pre-treated black garlic (BG) extracts addition into retorted Korean ginseng chicken soup (Samgyetang) on the fatty acid composition and flavour-related indexes. Methods: Four different treatments; Samgyetang made with a 5% (w/w) addition of garlic (G), fresh BG (FBG), oven-dried BG (DBG), or encapsulated BG (EBG) extracts were developed and compared to negative control (NC) without any extract addition. Prepared samples were cooked via retorting at 121.1℃, 1.5 kgf/cm² for 1 h. Results: The BG treated samples were higher in C18:3n3 and C18:2n6 fatty acids, with thrombogenic index was 18% to 20% lower than the NC. EBG yielded the highest umami-related nucleotides (5'-guanosine monophosphate and 5'-inosine monophosphate) and modified some free amino acid (alyne, phenylalanine and leucine) thus possessed the highest equivalent umami concentration among samples. Some individual aldehydes (pentanal, hexanal, and heptanal) were lower, while furans and volatile sulfur compounds were higher than the NC and G treatment group, indicating a potential suppression of unpleasant flavour alongwith the intensificiation of favourable flavour from the addition of BG extracts into retorted Samgyetang. Conclusion: Taken together, the synergistic results of this study indicate that incorportating suitable pre-treatment of BG extract could be of critical importance for the development of the retorted Samgyetang with improved flavour and functionalities.

• Steel and Composite Structures
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• v.41 no.6
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• pp.899-910
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• 2021

A 4-unknown shear deformation theory is applied to investigate the vibration of functionally graded plates under thermal environment. The plate is fabricated from a functionally graded material mixed of ceramic and metal with continuously varying material properties through the plate thickness. Three types of thermal loadings, uniform, linear and nonlinear temperature rises along the plate thickness are taken into account. The present theory contains four unknown functions as against five or more in other higher order shear deformation theories. The through-the-thickness distributions of transverse shear stresses of the plate are considered to vary parabolically and vanish at upper and lower surfaces. The present model does not require any problem dependent shear correction factor. Analytical solutions for the free vibration analysis are derived based on Fourier series that satisfy the boundary conditions (Navier's method). Benchmark solutions are firstly considered to evaluate the accuracy of the proposed model. Comparisons with the solutions available in literature revealed the good capabilities of the present model for the simulations of vibration responses of FG plates. Some parametric studies are carried out for the frequency analysis by varying the volume fraction profile and the temperature distribution across the plate thickness.