• Nutrition Research and Practice
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• v.17 no.6
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• pp.1056-1069
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• 2023

BACKGROUND/OBJECTIVES: Grifola frondosa, commonly referred to as the maitake mushroom, has been studied extensively to explore its potential health benefits. However, its anti-inflammatory effects in skin disorders have not been sufficiently elucidated. This study aimed to elucidate the anti-inflammatory role of the ethanol extract of G. frondosa in atopic dermatitis (AD) using in vivo and in vitro models. MATERIALS/METHODS: We investigated its impact on skin and spleen inflammatory responses in Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in a mouse model. Additionally, we determined the immunosuppressive response and mechanism of G. frondosa by inducing atopic-like immune reactions in keratinocytes through tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. RESULTS: Our study revealed that G. frondosa ameliorates clinical symptoms in an AD-like mouse model. These effects contributed to the suppression of Th1, Th2, Th17, and Th22 immune responses in the skin and spleen, leading to protection against cutaneous inflammation. Furthermore, G. frondosa inhibited the production of antibodies immunoglobulin (Ig)E and IgG2a in the serum of AD mice. Importantly, the inhibitory effect of G. frondosa on inflammatory cytokines in TNF-α/IFN-γ-stimulated AD-like keratinocytes was associated with the suppression of MAPK (Mitogen Activated Protein Kinase) pathway activation. CONCLUSIONS: Collectively, these findings highlight the potential of G. frondosa as a novel therapeutic agent for AD treatment and prevention.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.21-26
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• 2011

Ceramide is an important lipid mediator of extracellular signals that control various cellular functions, including apoptosis. In this study, we showed that ceramide induced apoptosis in U373MG human glioblastoma cells associated with G1 cell cycle arrest. Treatment of cells with ceramide increased proapoptotic Bax expression and inhibited the expression of antiapoptotic Bcl-2 and Bcl-xL Ceramide also downregulated cyclin E, cyclin D1, cdk 2, and cdk4 which are involved in regulating cell cycle. In addition, ceramide suppressed phosphorylation of Akt, Bad, p70 S6 kinase, and 4E-BP1, suggesting the involvement of Akt/mTOR signaling pathway. Additionally, okadaic acid, an inhibitor of protein phosphatase 2A, partially blocked the ceramide mediated inhibition of phosphorylation of Akt and 4E-BP1. These results suggest that ceramide induces apoptosis in U373MG glioblastoma cells by regulating multiple signaling pathways that involve cell cycle arrest associated with Akt signaling pathway.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.38-43
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• 2020

Hand, foot, and mouth disease (HFMD) is caused by enterovirus 71 (EV71) in infants and children under six years of age. HFMD is characterized by fever, mouth ulcers, and vesicular rashes on the palms and feet. EV71 also causes severe neurological manifestations, such as brainstem encephalitis and aseptic meningitis. Recently, frequent outbreaks of EV71 have occurred in the Asia-Pacific region, but currently, no effective antiviral drugs have been developed to treat the disease. In this study, we investigated the antiviral effect of salvianolic acid B (SalB) on EV71. SalB is a major component of the Salvia miltiorrhiza root and has been shown to be an effective treatment for subarachnoid hemorrhages and myocardial infarctions. HeLa cells were cultured in 12-well plates and treated with SalB (100 or 10 ㎍/ml) and 10⁶ PFU/ml of EV71. SalB treatment (100 ㎍/ml) significantly decreased the cleavage of the eukaryotic eIF4G1 protein and reduced the expression of the EV71 capsid protein VP1. In addition, SalB treatment showed a dramatic decrease in viral infection, measured by immunofluorescence staining. The Akt signaling pathway, a key component of cell survival and proliferation, was significantly increased in EV71-infected HeLa cells treated with 100 ㎍/ml SalB. RT-PCR results showed that the mRNA for anti-apoptotic protein Bcl-2 and the cell cycle regulator Cyclin-D1 were significantly increased by SalB treatment. These results indicate that SalB activates Akt/PKB signaling and inhibits apoptosis in infected HeLa cells. Taken together, these results suggest that SalB could be used to develop a new therapeutic drug for EV71-induced HFMD.

• Nutrition Research and Practice
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• v.11 no.5
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• pp.357-364
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• 2017

BACKGROUND/OBJECTIVES: Oxidative stress is closely related with inflammation and development of many diseases. Black soybean seed coat contains high amount of anthocyanins, which are well-known for free radical scavenging activities. This study investigated inflammatory response and action mechanism of black soybean anthocyanins with regard to antioxidant activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. MATERIALS/METHODS: RAW 264.7 cells were treated with anthocyanins extracted from black soybean seed coats in a concentration range of 12.5 to $100{\mu}g/mL$. The production of reactive oxygen species (ROS), secretion of pro-inflammatory mediators and cytokines, and the signaling in the mitogen activated protein kinases (MAPKs) pathway were examined. RESULTS: Black soybean anthocyanins significantly decreased LPS-stimulated production of ROS, inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$, and pro-inflammatory cytokines, including tumor necrosis factor ${\alpha}$ and interleukin-6, in a dose-dependent manner without cytotoxicity (P < 0.001). Black soybean anthocyanins downregulated the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells (P < 0.001). Moreover, black soybean anthocyanins inhibited LPS-induced phosphorylation of MAPKs, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 (P < 0.001). CONCLUSION: These results suggest that black soybean anthocyanins exert anti-inflammatory activity by inhibiting ROS generation and subsequent MAPKs signaling, thereby inhibiting inflammatory responses.

• Molecules and Cells
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• v.44 no.8
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• pp.591-601
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• 2021

Cilia are highly specialized organelles that extend from the cell membrane and function as cellular signaling hubs. Thus, cilia formation and the trafficking of signaling molecules into cilia are essential cellular processes. TULP3 and Tubby (TUB) are members of the tubby-like protein (TULP) family that regulate the ciliary trafficking of G-protein coupled receptors, but the functions of the remaining TULPs (i.e., TULP1 and TULP2) remain unclear. Herein, we explore whether these four structurally similar TULPs share a molecular function in ciliary protein trafficking. We found that TULP3 and TUB, but not TULP1 or TULP2, can rescue the defective cilia formation observed in TULP3-knockout (KO) hTERT RPE-1 cells. TULP3 and TUB also fully rescue the defective ciliary localization of ARL13B, INPP5E, and GPR161 in TULP3 KO RPE-1 cells, while TULP1 and TULP2 only mediate partial rescues. Furthermore, loss of TULP3 results in abnormal IFT140 localization, which can be fully rescued by TUB and partially rescued by TULP1 and TULP2. TUB's capacity for binding IFT-A is essential for its role in cilia formation and ciliary protein trafficking in RPE-1 cells, whereas its capacity for PIP₂ binding is required for proper cilia length and IFT140 localization. Finally, chimeric TULP1 containing the IFT-A binding domain of TULP3 fully rescues ciliary protein trafficking, but not cilia formation. Together, these two TULP domains play distinct roles in ciliary protein trafficking but are insufficient for cilia formation in RPE-1 cells. In addition, TULP1 and TULP2 play other unknown molecular roles that should be addressed in the future.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.655-660
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• 2023

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

• BMB Reports
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• v.52 no.11
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• pp.647-652
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• 2019

G protein-coupled estrogen receptor (GPER) is known to play an important role in hormone-associated cancers. G-1, a novel synthetic GPER agonist, has been reported to exhibit anti-carcinogenic properties. However, the chemotherapeutic mechanism of GPER is yet unclear. Here, we evaluated GPER expression in human gastric cancer tissues and cells. We found that G-1 treatment attenuates GPER expression in gastric cancer. GPER expression increased G-1-induced antitumor effects in mouse xenograft model. We analyzed the effects of knockdown/overexpression of GPER on G-1-induced cell death in cancer cells. Increased GPER expression in human gastric cancer cells increased G-1-induced cell death via increased levels of cleaved caspase-3, -9, and cleaved poly ADP-ribose polymerase. Interestingly, during G-1-induced cell death, GPER mRNA and protein expression was attenuated and associated with ER stress-induced expression of PERK, ATF-4, GRP-78, and CHOP. Furthermore, PERK-dependent induction of ER stress activation increased G-1-induced cell death, whereas PERK silencing decreased cell death and increased drug sensitivity. Taken together, the data suggest that the induction of ER stress via GPER expression may increase G-1-induced cell death in gastric cancer cells. These results may contribute to a new paradigm shift in gastric cancer therapy.

• Toxicological Research
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• v.26 no.4
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• pp.261-266
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• 2010

In the workplace, the arsenic is used in the semiconductor production and the manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers may be exposed to airborne arsenic during its use in manufacturing. The purpose of this study was to evaluate the potential toxicity of particulate matters (PMs) doped with arsenic (PMs-Arsenic) using a rodent model and to compare the genotoxicity in various concentrations and to examine the role of PMs-Arsenic in the induction of signaling pathway in the lung. Mice were exposed to PMs $124.4{\pm}24.5\;{\mu}g/m^3$ (low concentration), $220.2{\pm}34.5\;{\mu}g/m^3$ (middle concentration), $426.4{\pm}40.3\;{\mu}g/m^3$ (high concentration) doped with arsenic $1.4\;{\mu}g/m^3$ (Low concentration), $2.5\;{\mu}g/m^3$ (middle concentration), $5.7\;{\mu}g/m^3$ (high concentration) for 4 wks (6 h/d, 5 d/wk), respectively in the whole-body inhalation exposure chambers. To determine the level of genotoxicity, Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital micronucleus (SMN) assay were performed. Then, signal pathway in the lung was analyzed. In the genotoxicity experiments, the increases of aberrant cells were concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus frequency at high concentration. The inhalation of PMs-Arsenic increased an expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated mammalian target of rapamycin (p-mTOR) at high concentration group. Taken together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful risk assessment in the workplace.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.8
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• pp.1075-1081
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• 2014

CRBP1 (cellular retinol binding protein 1) and CRBP3 (cellular retinol binding protein 3), are important components of the retinoid signaling pathway and take part in vitamin A absorption, transport and metabolism. Based on the role of vitamin A in chicken laying performance, we investigated the polymorphism of CRBP1 and CRBP3 genes in 349 chickens using single strand conformation polymorphism and DNA sequencing methods. Only one polymorphism was identified in the third intron of CRBP1, two polymorphisms were detected in CRBP3; they were located in the second intron and the third intron respectively. The association studies between these three SNPs and laying performance traits were performed in Erlang mountainous chicken. Notably, the SNP g.14604G>T of CRBP1 was shown to be significantly associated with body weight at first egg (BWFE), age at first egg (AFE), weight at first egg (WFE) and total number of eggs with 300 age (EN). The CRBP3 polymorphism g.934C>G was associated with AFE, and the g.1324A>G was associated with AFE and BWFE, but none of these polymorphisms were associated with egg quality traits. Haplotype combinations constructed on these two SNPs of CRBP3 gene were associated with BWFE and AFE. In particular, diplotype H2H2 had positive effect on AFE, BWFE, EN, and average egg-laying interval. We herein describe for the first time basic research on the polymorphism of chicken CRBP1 and CRBP3 genes that is predictive of genetic potential for laying performance in chicken.

• Development and Reproduction
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• v.16 no.1
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• pp.69-75
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• 2012

Hatching occurred in the time dependent manners and strictly controlled. Although, the hatching processes are under the control of muti-embryotrophic factors and the expressed G proteins of cell generate integrated activation, the knowledge which GPCRs are expressed during hatching stage embryos are very limited. In the present study, which G proteins are involved was examined during blastocyst development to the hatching stage. The early-, expanded-, and lobe-stage blastocysts were treated with various $G_{\alpha}$ activators and H series inhibitors, and examined developmental patterns. Pertusis toxin (PTX) improved the hatching rate of the early-stage blastocyst and lobe-formed embryos. Cholera toxin (CTX) suppressed the hatching of the early-stage blastocyst and expanded embryos. The effects of toxins on hatching and embryo development were changed by the H7 and H8. These results mean that PTX mediated GPCRs activation is signaling generator in the nick or pore formation in the ZP. In addition, PTX mediated GPCR activation induces the locomotion of trophectoderm for the escaping. CTX mediate GPCRs activation is the cause of suppression of hatching processes. Based on these data, it is suggested that various GPCRs are expressed in the periimplantation stage embryos and the integration of the multiple signals decoding of various signals in a spatial and temporal manner regulate the hatching process.