• Clinical and Experimental Reproductive Medicine
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• 제48권4호
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• pp.352-361
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• 2021

Objective: The study assessed the developmental potential of germinal vesicle (GV) oocytes subjected to in vitro maturation (IVM) after prematuration culture with cilostamide (a phosphodiesterase-3 inhibitor) and the impact of cilostamide exposure on the morphology of meiosis II (MII) oocytes and subsequent embryo quality. Methods: In total, 994 oocytes were collected from 63 patients. Among 307 GV oocytes, 140 oocytes were selected for the experimental group and 130 oocytes for the control group. The denuded GV-stage oocytes were cultured for 6 hours with cilostamide in the experimental group and without cilostamide in the control group. After 6 hours, the oocytes in the experimental group were washed and transferred to fresh IVM medium. The maturational status of the oocytes in both groups was examined at 26, 36, and 48 hours. Fertilization was assessed at 18 hours post-intracytoplasmic sperm injection. Embryo quality was assessed on days 3 and 5. Results: In total, 92.1% of the oocytes remained in the GV stage, while 6.4% converted to the MI stage (p<0.01) after cilostamide exposure. In both groups, more MII oocytes were observed at 36 hours (25.8% vs. 21.5%) than at 26 hours (10.8% vs. 14.6%) and 48 hours (13% vs. 7.9%) (p>0.05). With the advent of cilostamide, blastocyst quality was better in the experimental group than in the control group (p<0.05). Conclusion: Cilostamide effectively blocked nuclear maturation and promoted cytoplasmic growth. Prematuration culture with cilostamide enabled synchronization between cytoplasmic and nuclear maturity, resulting in better blastocyst outcomes.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.31-31
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• 2018

Benign prostatic hyperplasia (BPH), which is the most common disorder in elderly men, involves androgenic hormone imbalance with chronic inflammation that causes imbalance between cell apoptosis and cell proliferation. As the root cause of the BPH remains unclear and synthetic drugs for treatment of BPH have undesirable side effects, the development of effective alternative medicines has been considered. Chinese Skullcap has been considered natural remedy to treat pyrexia, micturition disorder and inflammation. Although skullcap has effective properties on various diseases, the effects and molecular mechanism of Skullcap on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of Chinese Skullcap root extract (SRE) in testosterone-induced BPH rats. Compared with the untreated group, the SRE treatment group suppressed pathological alterations, such as prostate growth and increase in serum dihydrotestosterone and $5{\alpha}$-reductase levels. Furthermore, SRE significantly decreased the expression of androgen receptor and proliferating cell nuclear antigen. SRE also restored Bax/Bcl-2 balance. These effect of SRE was more prevalent than commercial $5{\alpha}$-reductase inhibitor, finasteride. Taken together, we propose that SRE suppresses abnormal androgen events in prostate tissue and inhibits the development of BPH by targeting inflammation- and apoptosis-related markers. These finding strengthens that SRE could be used as plant-based $5{\alpha}$-reductase inhibitory alternative.

• Nutrition Research and Practice
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• 제6권5호
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• pp.389-395
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• 2012

The study elucidated carbohydrase inhibition, anti-cancerous, free radical scavenging properties and also investigated the DNA and protein protection abilities of methanolic root extract of Rumex crispus (RERC). For this purpose, pulverized roots of Rumex crispus was extracted in methanol (80% and absolute conc.) for 3 hrs for $60^{\circ}C$ and filtered and evaporated with vacuum rotary evaporator. RERC showed high phenolic content ($211{\mu}g$/GAE equivalent) and strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ($IC_{50}$ = 42.86 (absolute methanol) and $36.91{\mu}g/mL$ (80% methanolic extract)) and reduced power ability. Furthermore, RERC exhibited significant protective ability in $H_2O_2/Fe^{3+}$/ascorbic acid-induced protein or DNA damage and percentage inhibition of the HT-29 cell growth rate following 80% methanolic RERC exposure at $400{\mu}g/mL$ was observed to be highest ($10.2%{\pm}1.03$). Moreover, methanolic RERC inhibited ${\alpha}$-glucosidase and amylase effectively and significantly (P < 0.05). Conclusively, RERC could be considered as potent carbohydrase inhibitor, anti-cancerous and anti-oxidant.

• 미생물과산업
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• 제19권4호
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• pp.32-35
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• 1993

ras는 활성화 형태인 GTP bound form과 비활성화 형태인 GDP bound form의 두 형태로 존재하며 두 형태를 매개하는 regulatory protein들에 의해 그 activity가 조절된다. 또한 ras는 GTP와 GDP에 강한 친화성이 있으며 세포내에는 GTP보다 GDP가 더 많이 있어서 평소에는 ras가 GDP와 결합하고 있다가 활성화될때만 GTP와 결합하는 것으로 추정된다. GDP bound ras는 guanine nucloetide exchange protein(GEP)에 의해 활성화된 GTP bound form으로 전환되며 ras의 기능이 발휘된 후에는 GTPase activating protein(GAP)에 의해 비활성화된다. Yeast의 경우 IRA1과 2의 product가 GAP의 역할을 하는 것으로 알려져 있고 CDC25 gene의 product가 GEP의 기능을 담당하는 것으로 알려져 있다. NF1 gene은 Von Recklinghausen Neurofibromatosis Type I 질병을 가진 환자에게서 발견되었는데 부분적으로 sequencing한 결과에 따르면 yeast의 IRA1/2, mammalian GAP gene product와 protein homology가 높은 것으로 나타났다. Yeast의 경우 IRA1/2 gene의 손실이나 mammalian ras gene의 transformation으로 인한 heat shock sensitivity가 NF1 gene(2,3) 혹은 GAP(4)의 expression으로 suppression된 것으로 보아 NF1이 GAP protein으로서 ras를 불활성화 시킨다는 것이 판명되었다. 결론적으로 ras의 활성은 GTP bound 혹은 GDP bound의 양쪽형태를 이동하면서 조절되는데 이 기능은 GAP과 GEP 또는 그의 유사 protein들에 의해 수행되며 이러한 regulatory protein들은 growth factor, cytokine 그리고 protein kinase 같은 signal에 의해 활성화된다고 생각된다. 본 총설에서는 ras protein의 여러가지 성질보다는 ras의 modification과 관련하여 항암제로 사용할 수 있는 ras에 specific한 약품개발의 가능성과 현재 알려진 ras의 inhibitor를 중심으로 논하고자 한다.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.331-336
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• 2010

In rapidly growing tumors, hypoxia commonly develops due to the imbalance between $O_2$ consumption and supply. Hypoxia Inducible Factor (HIF)-$1{\alpha}$ is a transcription factor responsible for tumor growth and angiogenesis in the hypoxic microenvironment; thus, its inhibition is regarded as a promising strategy for cancer therapy. Given that CamKII or PARP inhibitors are emerging anticancer agents, we investigated if they have the potential to be developed as new HIF-$1{\alpha}$-targeting drugs. When treating various cancer cells with the inhibitors, we found that a CamKII inhibitor, KN-62, effectively suppressed HIF-$1{\alpha}$ specifically in hepatoma cells. To examine the effect of KN-62 on HIF-$1{\alpha}$-driven gene expression, we analyzed the EPO-enhancer reporter activity and mRNA levels of HIF-$1{\alpha}$ downstream genes, such as EPO, LOX and CA9. Both the reporter activity and the mRNA expression were repressed by KN-62. We also found that KN-62 suppressed HIF-$1{\alpha}$ by impairing synthesis of HIF-$1{\alpha}$ protein. Based on these results, we propose that KN-62 is a candidate as a HIF-$1{\alpha}$-targeting anticancer agent.

• 동의생리병리학회지
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• 제17권2호
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• pp.568-573
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• 2003

We invesgated the GBH water extracts can be used as a potential cancer chemopreventive agent in humans, especially in hepatological cancer cell lines. The GBH was found to act as an potent inhibitor of COX-I only, but not as COX-2 inhibitor. Furthermore, the extract mediated anti-inflammatory effects and inhibited COX-associated hydroperoxidase functions(antipromotion activity). Inhibitory effect of the GBH water extracts on the growth of cancer cell lines such as HepG2 cell and Hep3B cell was shown.

• 대한의생명과학회지
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• 제16권2호
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• pp.71-74
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• 2010

Cell proliferation is governed by precise and orderly process the regulation of which involves many different proteins. The key enzyme for cell growth and arrest is cyclin dependent kinases (cdks). In human cells, several cdks orchestrate four distinct cell cycle phases (M, $G_1$, S and $G_2$ ) and they sequentially operate in an order of cdc1, cdk4, cdk6 and cdk2. The regulatory components of cdks consist of cyclins and two family of cdk inhibitors, INK4 (inhibitors of cdk4) and KIP (kinase inhibitor protein). $G_1$ regulatory molecules for cdk mainly respond to environmental cues of mitogenic and anti-mitogenic stimuli and therefore influence activities of $G_1$ cdks, namely, cdk4/6 and cdk2. $G_1$ inhibitors include $p21^{CIP}$ and $p27^{KIP1}$. Between them, $p27^{KIP1}$ has attracted attentions of many researchers because of its characteristic regulatory features and diverse functions. Besides, the role of $p27^{KIP1}$ in cancer development warrants further studies in the future. Therefore, this review will focus on the recent findings and especially on the complexity of regulatory mechanisms of $p27^{KIP1}$.

• Archives of Pharmacal Research
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• 제21권1호
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• pp.41-45
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• 1998

Hypericin, a photosensitizing plant pigment, was found to be a potent inducer of differentiation of human myeloid leukemia U-937 cells. At a concentration of $0.2{\mu}M$, hypericin exhibited 50% growth inhibition. An effect on cell differentiation by hypericin was assessed by its ability to induce phagocytosis of latex particles, and to reduce nitroblue tetrazolium (NBT). Approximately 51% of $0.2{\mu}M$ hypericin-treated cells were stained with NBT and 63% showed phagocytic activity. In order to establish whether hypericin induces differentiation of U-937 cells to macrophage or granulocyte, esterase activities and cell sizes were measured. When U-937 cells were treated with $0.2{\mu}M$ and $0.15{\mu}M$ of hypericin, the .alpha.-naphthyl acetate esterase activity was increased by 38.4% and 48.1%, respectively, but naphthol AS-D chloroacetate esterase activity was not influenced. The size of hypericin-treated cells in terms of cell mass was larger than that observed in untreated cells as determined by flow cytometry. Protein kinase C (PKC) inhibitor, NA-382, decreased the NBT reducing activity of hypericin, whereas a cAMP-dependent protein kinase A (PKA) inhibitor, H-89, did not show any influence on the differentiations. These results indicate that hypericin triggers differentiation toward monocyte/macrophage lineage by PKC stimulation.

• Journal of Microbiology
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• 제33권4호
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• pp.315-321
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• 1995

The relationship between morphological differentiation and production of trypsin-like protease (TLP_ in streptomycetes was studied. All the Streptomyces spp.In this study produced TLP just before the onset of aerial mycelium formation. Addition of TLP inhibitor, TLCK, to the top surface of colonies inhibited aerial mycelium formation as well as TLP inhibitor, TLCK, to the top surface of colonies inhibited aerial mycelium formation as well as TLP activity. Addition of 2% glucose to the Bennett agar medium repressed both the aerial mycelium formation and TLP production in S. abuvaviensis, S. coelicolor A3(2), S exfoliatus, S. microflavus, S. roseus, s. lavendulae, and S. rochei. However the addition of glucose did not affect S. limosus, S. felleus, S. griseus, S. phaechromogenes, and S. rimosus. The glucose repression on aerial mycelium formation and production of TLP was relieved by the addition of glucose anti-metabolite (methyl .alpha.-glucopyranoside). Therefore, it was concluded that TLP production is coordinately regulated with morphological differentiation and TLP activity is essential for morphological differentiation in streptomycetes. The proposed role of TLP is that TLP participates in the degradation of substrate mycelium protein for providing nutrient for aerial mycelial growth.

• 한국한의학연구원논문집
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• 제4권1호통권4호
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• pp.129-138
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• 1998

Angiogenesis, the formation of new blood vessels, is considered to be involved in many pathological symptoms such as diabetic retinopathy, arthritis, inflammation and solid tumour. In particular, it is thought that angiogenesis is critical for development and growth of solid tumour. Recent study shows that there is a highly significant association of microvessel density with overall survival and relapse-free survival in patients with breast tumour In this study, the inhibition effect of angiogenesis of traditional herbs used for the treatment of cancer was examined. It was found out that the extract of Agaricus blazei by boiling water is a possible inhibitor of angiogenesis. It inhibited normal developmental angiogenesis In the chorioallantoic membrane of chick embryos and also inhibited capillary-like tube formation by endotherial cells on matrigel in vitro. These results suggest that Agaricus blazei can be a potent angiogenesis inhibitor.