• Molecules and Cells
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• 제37권12호
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• pp.857-864
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• 2014

Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the antiapoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADPribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.

• Journal of Acupuncture Research
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• 제31권1호
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• pp.95-103
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• 2014

Objectives : The aim of this study is to evaluate the effect of Paljeong-san pharmac-opuncture(PJS) on the rat model of benign prostatic hyperplasia(BPH). Methods : Rats were divided into 5 groups, with 6 rats in each group. The 5 groups included sham-operated group(sham group), BPH model group(BPH group), finasteride-treated group (fina group), PJS-treated groups(PJS 10 and PJS 100 group). Testosterone was injected subcutaneously to the castrated rats except sham group for BPH model. During 4-week experimental period, finasteride(5 mg/kg) was administrated orally once daily in fina group, PJS in PJS 10(10 mg/kg) and PJS 100(100 mg/kg) group and normal saline in sham and BPH group were injected subcutaneously once daily at Jungwan($CV_{12}$). We checked prostate weights, serum concentration of dihydrotestosterone(DHT), morphologic changes of the prostate, and the amount of expression of the proliferating cell nuclear antigen(PCNA) and $5{\alpha}$-reductase gene to evaluate the effect of PJS after 4-week experimental period. Results : 1. PJS and finasteride treatment reduced prostate weights comparing with BPH group, but PJS-treated groups showed no significant changes, unlikely fina group. 2. PJS-treated groups showed significant degreases in concentration of DHT. 3. PJS-treated groups showed significant degreases concentration-dependently in the amount of expression of the PCNA and $5{\alpha}$-reductase gene. 4. PJS treatment showed shrinking of thickness in the prostatic epithelial tissue. Conclusions : PJS has the effects that improve the symptoms of BPH through inhibiting proliferation of the prostatic tissues.

• Clinical Pain
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• 제19권2호
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• pp.80-89
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• 2020

Objective: We compared the regenerative effects of microcurrent therapy (MT) according to the type of electric current, which were direct current microcurrent therapy (DCMT) and alternating current microcurrent therapy (ACMT) on atrophied calf muscle in cast-immobilized rabbit. Method: Rabbits were allocated into control group (sham MT), ACMT group, and DCMT group. Before starting treatment, right gastrocnemius (GCM) muscle was immobilized by cast for 2 weeks. Compound muscle action potential of tibial nerve in nerve conduction study, circumference of calf muscle using a ruler, and thickness of medial and lateral GCM muscle measured by ultrasound, cross sectional area (CSA), and proliferating cell nuclear antigen (PCNA) ratios (%) of muscle fibers were measured on the immunohistochemical analysis. Results: The mean atrophic changes (%) in right medial and lateral GCM muscle thickness, right calf circumference, and amplitude of CMAP of the right tibial nerve in ACMT group and DCMT group were significantly lower than those in control group, respectively (p<0.05). The mean CSA (μm²) of type I and type II and PCNA ratios (%) of medial and lateral GCM muscle fibers in ACMT group and DCMT group were significantly greater than those in control group, respectively (p<0.05). There were no significant differences between the ACMT group and DCMT group at all parameters. Conclusion: This study demonstrated that ACMT and DCMT showed better regeneration effect than sham MT. Microcurrent may be effective in regeneration of atrophied muscle regardless of the type of current.

• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.421-426
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• 2015

The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through $G_0/G_1$ to S phase of the cell cycle, as measured by [$^3H$]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at $G_0/G_1$ phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

• 생명과학회지
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• 제28권10호
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• pp.1220-1232
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• 2018

본 연구는 토끼의 상악동에 Bio-Oss와 ${\beta}-TCP$를 이식한 후 골 재생 과정을 조직학적으로 비교하기 위하여 수행되었다. 12마리의 수컷 토끼를 4마리씩 3군으로 구분하였다. 토끼의 양쪽 상악동 점막을 거상한 후 한쪽은 Bio-Oss를 이식하였고, 다른 쪽은 ${\beta}-TCP$를 이식한 후 본래의 골편으로 창을 봉합하였다. 2주, 4주 및 8주 후에 토끼를 희생시키고 조직절편을 만든 후 Bio-Oss군과 ${\beta}-TCP$군의 골 재생 양상을 비교하였다. 조직계측학적 분석을 위하여 각각의 조직절편에 hematoxylin-eosin, Masson trichrome 및 tartrate-resistant acid phosphatase 염색을 하였고, proliferating cell nuclear antigen (PCNA), type I collagen 및 osteocalcin의 발현 양상을 비교하기 위하여 면역조직화학 염색을 하였다. 광학현미경 시야에서 계측프로그램을 이용하여 계측하고 분석하여 다음과 같은 결과를 얻었다. Bio-Oss군과 ${\beta}-TCP$군 모두 2주군에서 초기 골 형성이 시작되었고, 4주군에서는 각 이식재 입자의 표면에 형성된 다량의 신생골이 관찰되었으며, 8주군에서는 신생골의 골량이 더 증가되어 있었고 층판골과 골수조직도 관찰되었다. 신생골의 양은 4주군까지 두 군이 비슷하였으나, 8주군에서는 ${\beta}-TCP$군에서 유의한 증가가 계측되었다. 이식재의 양은 4주군부터 8주군까지 ${\beta}-TCP$군에서 유의하게 감소되었으며, 파골세포의 수는 4주군에서 8주군까지 ${\beta}-TCP$군에서 유의하게 증가되어 있었다. PCNA에 대한 면역반응성은 8주군에서 감소되었지만 두 군간의 유의한 변화는 없었다. Type I collagen의 발현은, 2주군에서는 ${\beta}-TCP$군에서 유의하게 증가되었지만, 8주군에서는 Bio-Oss군에서 유의한 증가가 관찰되었다. Osteocalcin에 대한 면역반응성은 8주까지 증가되었으며 두 군간의 유의한 차이는 없었다. 이러한 조직학적 결과들은 임플란트를 위한 이식재의 선택에 도움을 줄 수 있다. 이상의 결과들을 종합하면 Bio-Oss와 ${\beta}-TCP$는 모두 검증된 이식재 이지만, 토끼의 상악동 거상술에서는 ${\beta}-TCP$가 좀 더 우수한 골 재생 결과를 보였다.

• 약학회지
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• 제50권2호
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• pp.84-92
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• 2006

The present study investigated an effect of arsenic trioxide on the urethane-induced lung carcinogenesis in mice. To understand its carcinogenesis, we examined proliferating cell nuclear antigen (PCNA), apoptotic index as well as cell cycle-related proteins (cyclin D1, p21, and p27). Urethane was injected intraperitoneally in ICR mice, and then they were sacrificed at 5, 15, or 25 weeks following treatment of arsenic trioxide. Arsenic trioxide was given with tap water at a concentration of 1 mg/l (low-dose) and 5mg/1 (high-dose) for 25 weeks. During the carcinogenesis, sequential histological changes from hyperplasia to adenomas, and ultimately to overt carcinomas were noted. The development of hyperplasias, adenomas, and carcinomas in the lung were slightly increased by the treatment of low-dose arsenic trioxide. However, there is no correlation between dose and tumor multiplicity. The administration of low-dose arsenic trioxide, significantly increased the tumor size. The proliferative index observed on 5 weeks after significantly increased. Cyclin D1 and p21 protein, cell cycle related proteins, were more significantly increased in hyperplasia and adenoma in low dose arsenic treated group than urethane alone group. The p27 protein expression did not show any significantly changes with arsenic treated or untreated group. Low dose exposure to arsenic trioxide resulted in increased expression of cyclin D1 and p21 protein. The present results indicate that low-dose treatment of arsenic trioxide, but not high dose of it, partly modulate the cellular proliferation, cyclin D1, and p21 protein expression, and that this effect may contribute to accelerated development of lung adenocarcinomas in urethane-induced mice.

• Animal Bioscience
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• 제35권7호
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• pp.989-998
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• 2022

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW^0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW^0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

• Molecules and Cells
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• 제39권5호
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• pp.418-425
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• 2016

Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neural-lineage differentiation in human umbilical cord derived MSCs (hUC-MSCs) in vitro at concentrations ranging from 0.1 to $10{\mu}M$, and whether it exerts the effects by modulating the SIRT1 signaling. Herein, we demonstrated that RES at the concentrations of 0.1, 1 and $2.5{\mu}M$ could promote cell viability and proliferation, mitigate senescence and induce expression of SIRT1 and Proliferating Cell Nuclear Antigen (PCNA) while inhibit the expression of p53 and p16. However, the effects were reversed by 5 and $10{\mu}M$ of RES. Furthermore, RES could promote neural differentiation in a dose-dependent manner as evidenced by morphological changes and expression of neural markers (Nestin, ${\beta}III-tubulin$ and NSE), as well as pro-neural transcription factors Neurogenin (Ngn)1, Ngn2 and Mash1. Taken together, RES exerts a dosage-dependent effect on the self-renewal and neural differentiation of hUC-MSCs via SIRT1 signaling. The current study provides a new strategy to regulate the fate of hUC-MSCs and suggests a more favorable in vitro cell culture conditions for hUCMSCs-based therapies for some intractable neurological disorders.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5331-5339
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• 2013

Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post-initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant ($p{\leq}0.05$) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferase and reduced glutathione. Whereas the supplementation of ACME significantly ($p{\leq}0.05$) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

• Molecules and Cells
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• 제45권12호
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• pp.935-949
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• 2022

Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of β-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)- related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.