• 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.

• 한국수의병리학회지
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• 제3권2호
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• pp.87-91
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• 1999

The present study was undertaken to compare the variation on serum biochemical values by storage in the rats. Sera were prepared from 30 Sprague-Dawley rats of each sex. 5 aliquots from each serum were placed in a -80$^{\circ}C$ freezer with the exception of I aliquots which was analyzed immediately. The analysis was performed on the following months; 1, 2, 3, 6, and 12 months after freezing. The parameters measured) were aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), blood urea nitrogen(BUN) creatinine(CRE), glucose(GLU), total cholesterol(TCHO), triglyceride (TG), total protein(TP), albumin(ALB), total bilirubin(TBIL), calcium(Ca$\^$＋＋/), inorganic phosphorus(IP), creatine kinase (CK), phospholipid(PL), albumin-globulin ratio(A/G), sodium(Na$\^$＋/), potassium(K$\^$＋/), and chloride(Cl$\^$－/) The statistical analysis with Repeated Measures ANOVA, did not show statistical significance in the parameters of AST, ALT, BUN, TG, CK, A/G, Na$\^$＋/ of 1 month freezed sera, in those of AST, TG, CK, K$\^$＋/) of 2 month freezed sera, in those of AST, ALT, BUN, CRE, TCHO, TP, TBIL, CK, PL, Na$\^$＋/), K$\^$＋/), Ct on month fteezed sera, in those of Cl$\^$－/ of 6 month fteezed sera, and in those of ALT, TG, ALB of 12 month freezed sera in male SD rats. On the other hand, it did not show statistical significance in the parameters of AST, ALT, ALP, BUN, GLU, TCHO, TG, TBIL, CK, PL, A/G, Na$\^$＋/ of 1 month freezed sera, in those of AST, TCHO of 2 month freezed sera, in those of AST, BUN, CRE, TCHO, TP, TBIL, CK, PL of 3 month freezed sera, in those of TCHO, IP, PL of 6 month freezed sera, and in those of ALB of 12 month freezed sera in female SD rats. On the basis of the results, although there are some statistical variations in the biochemical values of the sera, it is suggested that if sera are analysed at the same time before 12 months storage in a －80 $^{\circ}C$ freezer, the storing time does not affect the biochemical evaluation of the sera in SD rats.

• 한국잡초학회지
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• 제14권1호
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• pp.16-22
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• 1994

경기도 광주군 및 연천군 일원에서 채취한 93종의 잡초종(雜草種)을 대상으로 항균활성(抗園活性), 항종양활성(抗腫瘍活性), 항산화활성(抗酸化活性), 제초활성(除草活性) 등 몇가지 생리활성(生理活性)을 조사함으로써 제초(雜草)의 유용적(有用的)인 측면(則面)의 확인 뿐 아니라 나아가서 잡초(雜草)로부터 새로운 생리활성물질탐색(生理活性物質探索)의 가능성(可能性)을 제시하고자 하였다. 곰팡이에 있어서 사과나무 점무늬낙엽병균(落葉病菌)에 대해서는 새삼, 고추 역병균(疫病菌)에 대해서는 돼지풀과 쥐손이풀, 참깨 역병균(疫病菌)에 대해서는 쑥부쟁이와 미국쑥부쟁이가 항균활성(抗菌活性)을 나타내었다. 세균에 있어서는 돼지풀, 쑥, 사철쑥, 여뀌바늘, 구절초, 쥐손이풀, 미국가막사리 등이 비교적 항균활성(抗菌活性)의 범위(範圍)가 넓었으며 개비름, 비름, 망초, 물질경이, 쇠무릎, 물봉선, 벼룩나물 등이 Gram 양성세균인 Bacillus subtilis PCI219에 대하여 선택적(選擇的)인 항균활성(抗菌活性)을 나타내었다. 그리고 새삼, 개가장, 갈대, 쉽사리, 기름나물 등이 세포벽(細胞壁) 결손(缺損) 변이주(變異洙)인 Pseudomonas aeruginosa N10 균주에 대하여 선택적(選擇的)인 항균활성(抗菌活性)을 나타내었다. K562 세포(細胞)에 대한 protein kinase C 활성(活性)으로 조사한 antibleb 활성(活性)은 큰개여뀌, 사철쑥, 국화방망이, 개가장, 쥐손이풀, 바늘사초 등에서 나타났으며 특히 큰개여뀌에서는 조시료(粗試料) 상태에서 10mg/ml 농도(濃度)에서도 강한 활성(活性)을 나타내었다. 항산화활성(抗酸化活性)에 있어서는 바디나물, 쇠뜨기, 승마, 큰개여뀌, 쥐손이풀, 달맞이꽃, 방동사니대가리 등이 비교적 강한 활성(活性을) 나타내었으며 제초활성(除草活性)에 있어서는 여뀌바늘, 기름나물 등이 비교적 강한 활성(活性)을 나타내었다.

• 생명과학회지
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• 제21권11호
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• pp.1549-1557
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• 2011

TRAIL은 다양한 암세포에서 apoptosis를 유발하는 것으로 알려져 있으나 간암세포를 포함한 일부 암세포에서 TRAIL 저항성이 획득된 것으로 보고되어지고 있다. 대두의 대표적인 생리활성 물질인 isoflavonoid계열 genistein은 이미 많은 암세포에서 apoptotic 효능을 가진 것으로 알려져 있으나 TRAIL에 의한 apoptosis 유도에 미치는 영향과 기전에 대한 연구는 여전히 미비한 실정이다. 본 연구에서는 TRAIL 저항성을 가진 Hep3B 간암세포에서 TRAIL에 의한 apoptosis 유도를 genistein이 더욱 상승시킬 수 있음을 보고하고자 한다. 본 연구의 결과에 의하면, Hep3B 세포에 세포독성을 보이지 않는 범위의 genistein에 의한 TRAIL 유도 apoptosis 상승효과는 미토콘드리아의 기능 손상과 연관성이 있었다. 또한 genistein과 TRAIL 복합처리에 의한 apoptosis 유도는 p38 MAPK 활성 저하로 더욱 상승하였으며, 이는 Bid의 truncation 증가, pro-apoptotic 단백질인 Bax의 발현 증가와 anti-apoptotic Bcl-2의 발현 감소 및 미토콘드리아에서 세포질로의 cytochrome c 유출의 증가와 연관성이 있었다. 또한 p38 MAPK 억제제는 genistein 및 TRAIL 복합처리에 의한 caspase의 활성 증가와 PARP 단백질의 단편화를 촉진시켰으며, 이는 미토콘드리아의 기능적 손상 증가에 의한 것임을 알 수 있었다. 따라서 본 연구의 결과는 genistein이 TRAIL에 의한 apoptosis 유도를 효과적으로 증가시킬 수 있으며, 이러한 과정이 p38 MAPK 의존적으로 이루어짐을 알 수 있었다.

• 사상체질의학회지
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• 제15권1호
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• pp.72-89
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• 2003

To elucidate the neuroprotective effect of Yeoldahanso-tang(YHT) on nerve cells damaged by hypoxia, the cytotoxic effects of exposure to hypoxia were determined by XTT(SODIUM3,3'-{I-[(PHENYLAMINO) CARBONYL]-3,4-TETRAZOLIUM}- BIS (4-METHOXY-6-NITRO) BENZENE SULFONIC ACID HYDRATE), NR(Neutral red), MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and SRB(Sulforhodamin B) asssay. The activity of catalase and SOD(Superoxide dismutase) was measured by spectrophometry, and $TNF-{\alpha}$(Tumor cell necrosis $fector-{\alpha}$) and PKC(Protein kinase C) activity was measured after exposure to hypoxia and treatment of YHTWE. Also the neuroprotective effect of YHTWE was researched for the elucidatioion of neuroprotective mechanism. The results were as follows; 1. Hypoxia decreased cell viability measured by XTT, NR assay when cultured cerebral neurons were exposed to 95% N2/5% CO2 for $2{\sim}26$ minutes in these cultures and YHTWE inhibited the decrease of cell viability. 2. H2O2 treatment decreased cell viability measured by MTT, and SRB assay when cultured cerebral neurons were exposed to 1-80 ${\mu}M$ for 6 hours, but YHTWE inhibited the decrease of cell viability. 3. Hypoxia decreased catalase and SOD activity, and also $TNF-{\alpha}$ and PKC activity in these cultured cerebral neurons, but YHTWE inhibited the decrease of the catalase and SOD activity in these cultures. 4. Hypoxia triggered the apoptosis via caspase activation and internucleosomal DNA fragmentation. Also hypoxia stimulate the release of cytochrome c forom mitochondria. YHTWE inhibited the apoptosis via caspase activation induced by hypoxia. From these results, it can be suggested that brain ischemia model induced hypoxia showed neurotoxicity on cultured mouse cerebral neurons, and the YHTWE has the neuroprotective effect in blocking the neurotoxicity induced by hypoxia in cultured mouse cerebral neurons.

• Animal Bioscience
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• 제35권3호
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• pp.367-376
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• 2022

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry as well as the economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for HPAIV resistance. Therefore, in this study, we investigated gene expression related to cytokine-cytokine receptor interactions by comparing resistant and susceptible Ri chicken lines for avian influenza virus infection. Methods: Ri chickens of resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) lines were selected by genotyping the Mx dynamin like GTPase (Mx) and major histocompatibility complex class I antigen BF2 genes. These chickens were then infected with influenza A virus subtype H5N1, and their lung tissues were collected for RNA sequencing. Results: In total, 972 differentially expressed genes (DEGs) were observed between resistant and susceptible Ri chickens, according to the gene ontology and Kyoto encyclopedia of genes and genomes pathways. In particular, DEGs associated with cytokine-cytokine receptor interactions were most abundant. The expression levels of cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and IL-18), chemokines (C-C Motif chemokine ligand 4 [CCL4] and CCL17), interferons (IFN-γ), and IFN-stimulated genes (Mx1, CCL19, 2'-5'-oligoadenylate synthase-like, and protein kinase R) were higher in H5N1-resistant chickens than in H5N1-susceptible chickens. Conclusion: Resistant chickens show stronger immune responses and antiviral activity (cytokines, chemokines, and IFN-stimulated genes) than those of susceptible chickens against HPAIV infection.

• Journal of Nutrition and Health
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• 제56권2호
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• pp.123-139
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• 2023

구기엽 추출물 (LLE)과 클로로필을 제거한 구기엽 추출물 (LLE(Ch^-))이 MCD diet로 비알코올성 지방간을 유도한 C57BL/6 mouse와 팔미트산으로 지방 축적을 유도한 HepG2 세포에서 지방축적의 억제에 미치는 영향을 검토하였다. 대조군 대비 LLE(Ch^-)는 혈장 TG 농도와 혈장 AST와 ALT의 활성을 유의하게 감소시켰으며 LLE군에서는 혈장 ALT 활성이 유의하게 감소하였다. 두 군 모두 간조직의 TG와 cholesterol 함량을 유의하게 낮추었으며 간조직의 병리학적 변화 결과에서 LLE군에 비해 LLE(Ch^-)군에서 지방축적의 억제효과가 더 크게 나타났다. 팔미트산 0.5 mM을 처리한 HepG2 세포에서 LLE와 LLE(Ch^-)가 1,000 ㎍/mL 농도까지 독성이 없었으며 대조군에 비하여 각각 200 ㎍/mL과 500 ㎍/mL 농도부터 세포 내 지방 축적량을 유의하게 감소시켰고 pAMPK와 pACC 발현이 농도 의존적으로 증가하였으며 FAS발현은 농도 의존적으로 억제되었다. 결과적으로 구기엽 100% 에탄올 추출물들은 간조직의 지방 축적을 억제할 수 있으며 그 효과는 클로로필 제거 구기엽의 활성이 좀 더 큰 것으로 나타났다. 따라서 이 두 소재 모두 항 지방간 효능이 있는 것으로 판단되며 기능성 소재로서의 개발 가능성을 확인하였다.