• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7763-7768
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• 2014

Background: Gastritis and gastric cancer are the most common diseases in the Kazakh population. Polymorphisms in genes coding of cytokines have been played important role with gastric disease risk. The risk alleles of cytokines in patients with gastritis can predict the risk of developing gastric cancer. The aim of this study was to investigate cytokine gene polymorphisms as risk factors for the development of gastritis in a case-control study with gastritis patients and healthy individuals from the Kazakh ethnic group, living in North Kazakhstan. Materials and Methods: The polymerase chain reaction followed by direct sequencing were used for detection of two functional polymorphisms in the IL1 gene family, and TaqMan SNP Genotyping Assay Sets were applied for three potentially functional polymorphisms in the IL10 gene, and one in the TNFA promoter. Results: Association analysis of studied allelic variants and the development of gastritis in H. pylori-positive patients showed that IL1B -31C/C, IL1B -511T/T and IL1RN -2/2 allelic variants were associated with development of gastritis (OR=1.8 (1.07-3.16), p=0.025; OR=1.7 (1.04-2.99), p=0.035, and OR=4.92 (2.45-9.85), p<0.001) respectively. Haplotype C-Т that combines both homozygous allelic variants of IL1B gene also had a statistically significant association with slightly higher OR (OR: 1.43, 95% CI: 1.08-1.88). Conclusions: The data from the current study showed that the genotype IL-1B -511Т/-31C-IL1-RN-2 and H. pylori infection increase risk of gastritis in the Kazakh population. That genotype combination might be a factor increasing the risk of developing gastric cancer.

• BMB Reports
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• v.38 no.4
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• pp.447-456
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• 2005

TNF-$\alpha$ plays a pivotal role in inflammation processes which are mainly regulated by endothelial cells. While TNF-$\alpha$ induces apoptosis of several cell types like tumor cells, endothelial cells are resistant to TNFa mediated cell death. The cytotoxic effects of TNF-$\alpha$ on most cells are only evident if RNA or protein synthesis is inhibited, suggesting that de novo RNA or protein synthesis protect cells from TNF-$\alpha$ cytotoxicity, presumably by NF-${\kappa}B$ mediated induction of protective genes. However, the cytoprotective genes involved in NF-${\kappa}B$ dependent endothelial cell survival have not been sufficiently identified. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-$\alpha$ inducible genes in human arterial endothelial cells related to cell survival and cell cycle. The TNF-$\alpha$-induced expression of the RNA binding protein $p54^{nrb}$ and the 14-3-3 protein HS1 as shown here for the first time may contribute to the TNF-$\alpha$ mediated cell protection of endothelial cells. These genes have been shown to play pivotal roles in cell survival and cell cycle control in different experimental settings. The concerted expression of these genes together with other genes related to cell protection and cell cycle like DnaJ, $p21^{cip1}$ and the ubiquitin activating enzyme E1 demonstrates the identification of new genes in the context of TNF-$\alpha$ induced gene expression patterns mediating the prosurvival effect of TNF-$\alpha$ in endothelial cells.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.493-499
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• 2019

Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor $(NF)-{\kappa}B$ pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an $NF-{\kappa}B$ inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the $NF-{\kappa}B$ pathway during macrophage-mediated inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.5
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• pp.169-176
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• 2021

This study was conducted to suggest the Cudrania tricuspidata leaf and Achyranthes japonica Nakai Complex (CAC) possibility of use as a functional natural material for improving bone disease. Cudrania tricuspidata leaf and Achyranthes japonica Nakai were mixed in the same amount, extracted with hot water, and then powdered and used in the study. After, the cytotoxicity of CAC for osteoblasts (MG63 cell), osteoclasts (differentiated RAW264.7 cell), and macrophages (RAW264.7 cell) were evaluated by MTT assay, and ALP assay and TRAP assay were performed to confirm the differentiation capacity of osteoblasts and osteoclasts, respectively. In addition, the anti-inflammatory effect in macrophages was evaluated by ELISA, qRT-PCR, and western blot assay. CAC did not proliferated osteoblasts and osteoclasts, but increased ALP activity against osteoblasts differentiation and decreased TRAP activity against osteoclasts differentiation. CAC did not proliferated macrophages but decreased nitric oxide production. Also, decreased NOS2, IL1B, IL6, PTGS2, and TNFA gene expression, and JNK and p38 protein phosphorylation in a concentration-dependent manner, but ERK protein phosphorylation was not changed. As a result, CAC increased the differentiation and activation of osteoblasts, inhibited the differentiation and activation of osteoclasts, and regulated the expression of inflammatory cytokines in macrophages. Therefore, it is thought that CAC can be used as a functional natural material that prevents bone disease and has an anti-inflammatory effect.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.12-12
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• 2021

최근 길어진 여름 및 이상고온 현상이 지속됨에 따라 심화되는 광노화 피부의 특징으로는 건조, 굵고 깊은 주름, 탄력저하 및 불균일한 색소침착 등이 나타나게 됨. 화장품 소재는 기존 광노화 관련 화학물질인 Retinol 등을 대체하기 위해 자연 유래 성분을 적용한 신소재 연구를 진행하고 있음. 흰목이버섯(Tremella fuciformis)은 흰목이목에 속하는 버섯류로 자실체는 한천질로서, 주름이 되어 갈라져 있거나 또는 귓불 모양을 이루고 있으며, 크기는 10 cm 정도이다. 중국에서는 보양식의 주재료로 쓰일 만큼 탁월한 항노화 효능이 알려져 있다. 본 연구에서는 흰목이버섯의 자실체에서 추출하여 정제한 β-Glucan의 성분 확인, in vitro 수준의 피부 항노화 효과, 동물대체 독성 시험을 통한 피부독성 확인 및 인체 피부유효성 평가를 통한 항노화 효과를 확인하였다. 흰목이에서 추출, 정제 후 Bio-LC를 통한 유리당 분석 결과 Mannose, Fucose, Glucose를 확인하였으며, Human Keratinocyte에 UVB를 조사하여 광노화를 유발한 피부세포에 피부 자극 및 탄력저하 인자인 IL-6, TNFa 및 MMP-1을 평가한 결과 농도 의존적으로 현저히 개선됨을 확인하였다. 또한 보습 및 피부장벽 개선 인자인 Filaggrin과 Involucrin 생성효능을 평가한 결과 매우 높이 생성됨을 확인하였다. 본 연구결과를 토대로 광독성, 피부감작성 및 안점막 동물대체 독성시험을 실시한 결과 무독성임을 확인하여 피부에 안전하면서 효능이 우수한 것을 in vitro 수준에서 확인하였고, 피부 홍반완화, 주름개선, 탄력개선 및 보습증가 등 광노화 예방효과를 인체를 대상으로 평가한 결과 유의적인 홍반완화, 주름개선, 탄력 및 보습증가효과를 확인하였다. 본 연구결과를 종합하여 볼 때 흰목이버섯에서 추출, 정제한 β-Glucan은 in vitro 수준에서 자외선으로 인한 피부 트러블 완화, 탄력 및 보습개선을 확인하였고 독성시험을 통해 무자극임을 판정하였으며, 인체유효성 평가를 통해 광노화 예방효과를 확인하였으며 본 결과를 통해 아시아 및 글로벌 시장으로 천연유래 항노화 소재로 확장하고자 한다.

• Animal Bioscience
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• v.36 no.6
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• pp.851-860
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• 2023

Objective: This study aims to evaluate the target genes of gga-miR-20a-5p and the regulated immune responses in the chicken macrophage cell line, HD11, by the exosome-mediated delivery of miR-20a-5p. Methods: Exosomes were purified from the chicken macrophage cell line HD11. Then, mimic gga-miR-20p or negative control miRNA were internalized into HD11 exosomes. HD11 cells were transfected with gga-miR-20a-5p or negative control miRNA containing exosomes. After 44 h of transfection, cells were incubated with or without 5 ㎍/mL poly(I:C) for 4 h. Then, expression of target genes and cytokines was evaluated by quantitative realtime polymerase chain reaction. Results: Using a luciferase reporter assay, we identified that gga-miR-20a-5p directly targeted interferon gamma receptor 2 (IFNGR2), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase kinase kinase 5 (MAP3K5), and mitogen-activated protein kinase kinase kinase 14 (MAP3K14). Moreover, the exosome-mediated delivery of gga-miR-20a-5p successfully repressed the expression of IFNGR2, MAPK1, MAP3K5, and MAP3K14 in HD11 cells. The expressions of interferon-stimulated genes (MX dynamin like GTPase 1 [MX1], eukaryotic translation initiation factor 2A [EIF2A], and oligoadenylate synthase-like [OASL]) and proinflammatory cytokines (interferon-gamma [IFNG], interleukin-1 beta [IL1B], and tumor necrosis factor-alpha [TNFA]) were also downregulated by exosomal miR-20a-5p. In addition, the proliferation of HD11 cells was increased by exosomal miR-20a-5p. Conclusion: The exosome-mediated delivery of gga-miR-20a-5p regulated immune responses by controlling the MAPK and apoptotic signaling pathways. Furthermore, we expected that exosomal miR-20a-5p could maintain immune homeostasis against highly pathogenic avian influenza virus H5N1 infection by regulating the expression of proinflammatory cytokines and cell death.