• Tuberculosis and Respiratory Diseases
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• 제56권6호
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• pp.638-645
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• 2004

연구배경 : Uteroglobin은 정상 폐상피세포에서 발현되는 단백질로 비소세포암 조직이나 세포주에서는 발현이 저하되어있다. 항염증작용을 하며 암세포에 과발현 시키면 암의 형질이 소실됨이 밝혀지고 있다. 역시 염증작용과 관련이 있는 cPLA2와 COX-2도 암과의 관련성이 밝혀지고 있고, 암억제나 MMP의 억제 등의 공통점을 가지고 있으나 이들의 관련성에 대해서는 밝혀진 바가 없다. 또한, COX-2의 암과의 관련성을 설명하는 기전으로 ERK 활성화의 관련 가능성이 있으나, uteroglobin과 ERK의 관련성도 아직 밝혀지지 않고 있다. 비소세포폐암 세포주에 uteroglobin을 과발현시킨 후, cPLA2와 COX-2의 발현, 그리고 MMP-2, MMP-9, ERK의 활성화가 어떻게 변화하는지에 대해 실험하였다. 방 법 : 폐선암세포주인 A549와 NCI-H460 세포주에 adenovirus-uteroglobin, adenovirus-null을 각각 20,100,200 moi로 transduction 시킨 뒤, 48시간 배양한 후에 단백질을 추출하였다. Uteroglobin의 발현을 확인한 후, cPLA2, COX-2, pERK, total ERK에 대해 Western blot을 시행하였고, 배양액으로 zymography를 시행하였다. 결 과 : A549 세포주와 NCI-H460 세포주에서 uteroglobin의 발현을 확인한 세포주에서 cPLA2와 COX-2의 발현이 감소함을 Western blot으로 확인하였고, pERK가 증가함을 Western blot으로 보았고, ERK의 활성화가 증가함을 확인하였다. MMP-9은 활성이 저하되었고, MMP-2는 변화가 없었다. MEK inhibitor인 U0126을 이용하여 ERK의 활성화를 저해시킨 후, uteroglobin의 발현에는 영향이 없었고, MMP-9의 활성저하효과가 소실되었다. 결 론 : 폐암세포주에서 uteroglobin의 항암작용기전에 cPLA2 와 COX-2의 발현의 감소와 ERK의 활성화가 기여할 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제25권5호
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• pp.648-657
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• 2015

H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction, respectively; immunohistochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced the cleavage of proapoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly(ADP)-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosisinducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in the G1/S phase. In addition, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.

• 동의생리병리학회지
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• 제22권6호
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• pp.1500-1508
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• 2008

The author investigated whether Chwiyeon-tang(PC), Haengso-tang(PH), Jawanchihyo-san(PJ) and Gamisocheongryong-tang(PS) significantly affect both PMA-induced mucin production and MUC5AC gene expression in airway epithelial cells and sulfur-dioxide-induced airway goblet cell hyperplasia and mucus hypersecretion animal model using rat. Possible cytotoxicity of each herbal medicine was assessed by measuring the survival and proliferation rate of NCI-H292 cells. Confluent NCI-H292 cells were pretreated for 30 min in the presence of PC, PH, PJ and PS, respectively, and treated with PMA(10 $ng/m{\ell}$), to assess the effect of each herbal medicine on PMA-induced mucin production by enzyme-linked immunosorbent assay(ELISA). Effects of each herbal medicine on PMA-induced MUC5AC gene expression from the same cells were investigated. Also, hypersecretion of airway mucus and goblet cell hyperplasia were induced by exposure of rats to $SO_2$ during 3 weeks. Effects of orally-administered PC, PH, PJ and PS during 1 week on intraepithelial mucosubstances and hyperplasia of goblet cells were examined using histological analysis after staining the epithelial tissue with PAS-alcian blue. (1) PC, PJ, PS and PH did not show significant effects on the survival and proliferation of NCI-H292 cells ; (2) PC, PJ and PS significantly decreased PMA-induced mucin production from NCI-H292 cells ; (3) PC, PJ and PS significantly inhibit the expression levels of PMA-induced MUC5AC gene in NCI-H292 cells ; (4) Among PC, PJ, PS and PH, only PS decreased $SO_2$-induced hyperplasia of airway goblet cells and intraepithelial mucosubstances. This result suggests that PC, PJ and PS can not only affect the production of mucin but also affect the expression of mucin gene and this can explain, at least in part, the traditional use of PC, PJ and PS for controlling airway diseases showing hypersecretion of mucus in oriental medicine.

• Asian-Australasian Journal of Animal Sciences
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• 제33권5호
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• pp.704-711
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• 2020

Objective: Muscle fiber types, numbers and area are crucial aspects associated with meat production and quality. However, there are few studies of pig muscle fibre traits in terms of the detection power, false discovery rate and confidence interval precision of whole-genome quantitative trait loci (QTL). We had previously performed genome scanning for muscle fibre traits using 183 microsatellites and detected 8 significant QTLs in a White Duroc×Erhualian F₂ population. The confidence intervals of these QTLs ranged between 11 and 127 centimorgan (cM), which contained hundreds of genes and hampered the identification of QTLs. A whole-genome sequence imputation of the population was used for fine mapping in this study. Methods: A whole-genome sequences association study was performed in the F₂ population. Genotyping was performed for 1,020 individuals (19 F₀, 68 F₁, and 933 F₂). The whole-genome variants were imputed and 21,624,800 single nucleotide polymorphisms (SNPs) were identified and examined for associations to 11 longissimus dorsi muscle fiber traits. Results: A total of 3,201 significant SNPs comprising 7 novel QTLs showing associations with the relative area of fiber type I (I_RA), the fiber number per square centimeter (FN) and the total fiber number (TFN). Moreover, one QTL on pig chromosome 14 was found to affect both FN and TFN. Furthermore, four plausible candidate genes associated with FN (kinase non-catalytic C-lobe domain containing [KNDC1]), TFN (KNDC1), and I_RA (solute carrier family 36 member 4, contactin associated protein like 5, and glutamate metabotropic receptor 8) were identified. Conclusion: An efficient and powerful imputation-based association approach was utilized to identify genes potentially associated with muscle fiber traits. These identified genes and SNPs could be explored to improve meat production and quality via marker-assisted selection in pigs.

• 한국식품영양과학회지
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• 제45권4호
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• pp.474-483
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• 2016

본 연구에서는 마우스를 대상으로 enzymatically modified isoquercitrin(EMIQ)이 고지방식이에 의한 체중증가와 이와 관련된 혈중지표들의 변화에 미치는 영향을 알아보고, 지방조직을 중심으로 그 작용기작을 규명하고자 하였다. 10주간 고지방식이와 함께 섭취시킨 1.2% EMIQ는 마우스의 체중(-21%), 내장지방량(-31%) 그리고 혈중지표인 중성지방(-17%), 총콜레스테롤(-19%) 및 유리지방산(-26%)의 농도를 유의적으로 감소시켰다. 내장지방조직과 피하지방조직 모두에서 EMIQ는 PKA의 단백질량을 유의하게 증가시켰다. EMIQ는 또한 내장지방조직에서 지방생성 관련 유전자들의 발현($PPAR{\gamma}2$, $C/EBP{\alpha}$, FAS, aP2)을 유의하게 감소시킨 반면, 지방산 산화 관련 분자(p-HSL)를 유의하게 증가시켰고, 내장지방조직과 피하지방조직 모두에서 열발생 관련 유전자($PGC1-{\alpha}$, PRDM16, Cidea, UCP1)의 발현을 유의하게 증가시켰다. 따라서 EMIQ의 체중감소효능은 지방조직에서 PKA가 매개하는 지방생성, 지방산 산화 및 열 발생 관련 신호전달체계 유전자들의 발현변화와 관련이 있을 것으로 생각한다.

• 한국식품영양과학회지
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• 제33권8호
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• pp.1237-1245
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• 2004

브라질 기원인 신령 버섯 (A. blazei murill)은 강력한 항암 및 면역강화 작용을 가진 것으로 알려져 있다. 본 연구에서는 신령버섯 수용성 추출물(water extracted A. blazei Murill, WEAB)이 A549 인체 폐암세포 증식에 미치는 영향을 조사하였으며, 증식억제와 연관된 기전 해석을 시도하였다. WEAB가 처리된 A549 세포는 처리 농도 의존적으로 생존율이 감소되었으며, WEAB 처리는 암세포의 다양한 형태적 변형을 유발하였다. Flow cytometry 분석 결과로서 WEAB 처리에 의한 A549 폐암세포의 증식억제는 세포주기 G2/M arrest 및 apoptosis 유발과 직접적으로 연관성이 있음을 알 수 있었다. WEAB가 처리된 암세포에서 전사 및 번역 수준에서 cyclin A 발현의 감소 및 Cdk inhibitor p21 발현의 증가 현상이 관찰되었으나, cyclin B1, Cdk2, Cdc2, Wee1, Cdc25c 및 p53 등의 발현에는 큰 변화가 관찰되지 못하였다. 또한 WEAB의 처리는 COX-2 선택적 발현 저하를 유발하였으나, telomere 조절 관련 유전자들의 발현에는 큰 영향을 주지 못하였다. 이상의 결과는 신령버섯 추출물이 강력한 항암 및 암 예방 효능의 잠재력을 가지고 있음을 의미하며, 이에 관한 지속적인 연구가 필요할 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3595-3604
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• 2015

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

• Asian-Australasian Journal of Animal Sciences
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• 제31권4호
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• pp.595-606
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• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• 동의생리병리학회지
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• 제25권3호
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• pp.496-502
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• 2011

The present study was undertaken to investigate the effect of bee venom acupuncture therapy on the hair follicle growth by macroscopic, microscopic and immunohistochemical observation of skin 10 and 17 days after treatment. The results were as follows : Macroscopic hair follicle growth of 0.2 ml S.B.V. acupuncture treated group was more prominent than those of 0.1 ml S.B.V. acupuncture treated group and control group. Microscopic observation indicated that the hair follicle growth of control group reached anagen phase IV of hair growing cycle, and that of 0.1 ml and 0.2 ml S.B.V. acupuncture treated groups reached anagen phase VI and catagen, respectively. Immunohistochemical observations of the expression of various cytokines, enzymes and receptors in association with hair follicle cycle after local treatment of S.B.V. acupuncture therapy are as follows: Expression of fibroblast growth factor was more intense in epidermis and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than that of 0.1 ml S.B.V. acupuncture treated group and control group. Expression of epidermal growth factor was more intense in bulge and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than that of 0.1 ml S.B.V. acupuncture treated group and control group. Expression of c-kit receptor was more intense in epidermis, bulge and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than that of control group. Expression of vascular endothelial growth factor was more intense in epidermis, bulge and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than that of control group. Expression of protein kinase C-${\alpha}$ was more intense in epidermis, bulge and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than control group. It is concluded that bee venom acupuncture therapy promoted the expression of various cytokines, enzymes and receptors related to the hair growth cycle for hair growth. This findings indicates that bee venom acupuncture therapy is applicable to the treatment of hair loss.

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.299-306
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• 2013

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.