• 한국발생생물학회지:발생과생식
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• 제26권3호
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• pp.117-126
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• 2022

Bromodomain-containing protein 7 (BRD7) participates in many cellular processes and embryo development. BRD7 is down-regulated in various cancers and evidence of its tumor suppressor function has been accumulating. Here, we identified transforming stimulated clone 22 (TSC-22) as a novel BRD7 interacting protein and show its novel function as a positive regulator of BRD7. We found that TSC-22 expression potentiated the inactivation of the extracellular signal-regulate kinase (ERK) pathway by BRD7. Our data establishes TSC-22 as a modulator of BRD7 and unravels the molecular mechanisms that drive the synergistic tumor-suppressing effects of TSC-22 and BRD7. Our findings may open new avenues for developing novel molecular therapies for tumors exhibiting down-regulated BRD7 and/or TSC-22.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1615-1619
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• 2015

Background: Promoter hypermethylation mediated gene silencing of tumor suppressor genes is considered as most frequent mechanism than genetic aberrations such as mutations in the development of cancers. BRD7 is a single bromodomain containing protein that functions as a subunit of SWI/SNF chromatin-remodeling complex to regulate transcription. It also interacts with the well know tumor suppressor protein p53 to trans-activate genes involved in cell cycle arrest. Loss of expression of BRD7 has been observed in breast cancers and nasopharyngeal carcinomas due to promoter hypermethylation. However, the genetic status of BRD7 in oral squamous cell carcinomas (OSCCs) is not known, although OSCC is one of the most common among all reported cancers in the Indian population. Hence, in the present study we investigated OSCC samples to determine the occurrence of hypermethylation in the promoter region of BRD7 and understand its prevalence. Materials and Methods: Genomic DNA extracted from biopsy tissues of twenty three oral squamous cell carcinomas were digested with methylation sensitive HpaII type2 restriction enzyme that recognizes and cuts unmethylated CCGG motifs. The digested DNA samples were amplified with primers flanking the CCGG motifs in promoter region of BRD7 gene. The PCR amplified products were analyzed by agarose gel electrophoresis along with undigested amplification control. Results: Methylation sensitive enzyme technique identified methylation of BRD7 promoter region seventeen out of twenty three (74%) well differentiated oral squamous cell carcinoma samples. Conclusions: The identification of BRD7 promoter hypermethylation in 74% of well differentiated oral squamous cell carcinomas indicates that the methylation dependent silencing of BRD7 gene is a frequent event in carcinogenesis. To the best of our knowledge, the present study is the first to report the occurrence of BRD7and its high prevalence in oral squamous cell carcinomas.

• 한국축산식품학회지
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• 제38권4호
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• pp.703-710
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• 2018

Bromodomain-containing protein 2 (BRD2) is a nuclear serine/threonine kinase involved in transcriptional regulation. We investigated the expression and association of the BRD2 gene as a candidate gene for meat quality traits in Berkshire pigs. BRD2 mRNA was expressed at relatively high levels in muscle tissue. Statistical analysis revealed that the c.1709G>C polymorphism of the BRD2 gene was significantly associated with carcass weight, meat color ($a^*$, redness), protein content, cooking loss, water-holding capacity, carcass temperatures 4, 12 and 24 h postmortem, and the 24 h postmortem pH in 384 Berkshire pigs. Therefore, this polymorphism in the porcine BRD2 gene may be used as a candidate genetic marker to improve meat quality traits in pigs.

• 대한치과교정학회지
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• 제26권4호
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• pp.359-371
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• 1996

교정력에 의한 성견의 치아이동시 발생하는 조직변화 중 치주인대 내에서의 세포활성도의 변화를 교정력의 크기와 기간에 따라 알아 보고자 하였다. 생후 1년 6개월된 성견 6마리를 5마리의 실험군과 1마리의 대조군으로 나누었고 실험군에서 하악 좌측에는 강한 힘 (250-300g)을, 하악 우측에는 약한 힘 (50-75g)을 제1소구치와 제2소구치 사이에 open coil spring으로써 적용하였다. 실험군의 성견을 각각 12시간, 24시간, 3일, 1주, 2주에 Bromodeoxyuridine(BrdU)을 주입하고 희생시켰다. 하악 제 1,2 소구치 부위의 조직을 채득하여 통법에 따라 파라핀 포매하였으며, H & E 염색과 항 BrdU 항체를 이용한 면역조직화학적 염색을 시행한 결과 다음과 같은 결론을 얻었다. 견인측에서의 치주인대 단절과 혈관확장은 12시간째에서 관찰되어 증가하다가 3일째 이후에는 감소되었는데 약한 힘을 준 경우보다 강한 힘을 준 경우에서 더 많았으며 압박측에서의 치주인대의 초자양변성과 파골세포 활성은 12시간째에서부터 관찰되어 3일째까지 증가하다가 7일째부터 감소하였는데 약한 힘을 준 경우보다 강한 힘을 준 경우에서 더 많이 나타났다. 대조군의 BrdU 발현은 구강상피와 치주인대의 섬유모세포에서 주로 많았고 골세포나 파골세포에서는 음성 반응을 보였으며 실험군의 BrdU 발현은 압박 측보다 견인측에서 많았으며 치경부쪽보다는 치근단쪽에서 더 많았다. 약한 힘을 준 경우에서는 BrdU 발현이 1일째에 가장 많이 나타나다가 감소되었고 강한 힘을 준 경우에서는 12시간째에서 최고에 달하다가 이후에는 감소되었으나 14일째에는 실험군과 대조군 간에 큰 차이가 없었다.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.229-233
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• 2013

This study was aimed at investigating the possible effects of phytoceramide (Pcer) on learning and memory and their underlying mechanisms. Phytoceramide was orally administered to ICR mice for 7 days. Memory performances were assessed using the passive avoidance test and Y-maze task. The expressions of phosphorylated cAMP response element binding protein (pCREB), brain-derived neurotrophic factor (BDNF) were measured with immunoblot. The incorporation of 5-bromo-2-deoxyuridine (BrdU) in hippocampal regions was investigated by using immunohistochemical methods. Treatment of Pcer enhanced cognitive performances in the passive avoidance test and Y-maze task. Immunoblotting studies revealed that the phosphorylated CREB and BDNF were significantly increased on hippocampus in the Pcer-treated mice. Immunohistochemical studies showed that the number of immunopositive cells to BrdU was significantly increased in the hippocampal dentate gyrus regions after Pcer-treatment for 7 days. These results suggest that Pcer contribute to enhancing memory and BDNF expression and it could be secondary to the elevation of neurogenesis.

• 대한한의학회지
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• 제31권3호
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• pp.107-121
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• 2010

Objective: This study aimed to ascertain the curative effects of Gamisipjeon-tang (GST) used for wound healing on the skin regeneration of deep second degree burns in mice. Material & Methods: In vitro, the $I{\kappa}B$ kinase (IKK) mRNA expression, inducible nitric oxide synthase (iNOS) mRNA expression, and cyclooxygenase-2 (COX-2) mRNA expression in the GST concentration from 1 mg/$m{\ell}$ to 10 mg/$m{\ell}$ were measured. In vivo, the mice were divided into four groups : the normal group, the BE group (burn-elicited group, control group), the DC group (Duoderm CGF-treated group after burn elicitation), and the GST group (Gamisipjeon-tang treated group after burn elicitation). To determine the anti-inflammatory effects, nuclear factor (NF)-${\kappa}B$ p65, iNOS, COX-2 positive reaction were measured by immunohistochemistry. To estimate the skin regenerative effects, change of burn area, 5-bromo-2'-deoxyuridine (BrdU), and fibroblast growth factor (FGF) positive reaction were analyzed. Results: In vitro, the iNOS, IKK, COX-2 mRNA expression decreased according to the increase of GST concentration. The significant decrease of COX-2, iNOS, NF-${\kappa}B$ positive reaction were the highest in the GST group, followed by the DC group and the BE group (p<0.05). The diameter of burn area was significantly decreased in the GST group as compared to that in the DC and BE group (p<0.05). The BrdU and FGF positive reaction increased more significantly in the GST group than in the DC group, and more significantly in the DC group than in the BE group on the 3rd and 7th day after burn (p<0.05). FGF positive reaction increased in the BE and DC group, whereas it decreased significantly in the GST group on the 14th day (p<0.05). The BrdU positive reaction increased in the BE group, whereas it decreased significantly in the DC and GST group on the 14th day (p<0.05). Conclusions: This study shows that GST could decrease the inflammatory response and accelerate the skin regeneration as compared to the duoderm CGF in mice with deep second degree burns.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.94-94
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• 2003

Endocrine disrupters (EDs) are exogenous chemicals that interfere with the production, releasing, metabolism, excretion, binding of natural hormones, and whole endocrine systems. EDs are very dangerous since they are extremely stable, not easily degraded, and accumulated in fat and tissue. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is known as the most toxic EDs. Therefore, this study was conducted to investigate the effects of TCDD on proliferation of human breast cancer (MCF-7) and endometrial adenocarcinoma (Hec-1B) cells. 10, 100, and 1000 nM of TCDD were treated with steroid free condition. Viable cell counting, MTT, and BrdU assay was performed to investigate cell proliferation. Apoptosis was investigated using DNA laddering. Although, DNA fragmentation as the evidence of apoptosis was not detected, all of these cell lines showed restricted proliferation at 48 hrs after 100 and 1000 nM TCDD treatments. Recently, it has been reported that the expression of transforming growth factor $\beta$s (TGF-$\beta$s) are increased in TCDD treatment and also involved in regulation of cell cycle. Therefore, these results were considered that the decreased cell prolifcration by TCDD is related to the expression of TGF-$\beta$s.

• 대한약침학회지
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• 제19권2호
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• pp.122-128
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• 2016

Objectives: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. Methods: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. Results: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. Conclusion: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up-regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia.

• 대한약침학회지
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• 제18권4호
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• pp.20-25
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• 2015

Objectives: Recently, thread-embedding therapy (TET) has been widely applied in Korean medicine for cosmetic purposes such as reducing skin wrinkles. An inserted thread was reported to have induced continuous stimulation, followed by support for connective tissue regeneration. However, the potential role of TET in hair-growth has not yet been reported. Methods: We designed this study to evaluate whether TET has a hair-growth-promoting effect. C57 black 6 (C57BL/6) mice were divided into three groups: normal saline-treated, minoxidil-treated, and thread-embedded groups. Normal saline or 5% minoxidil was topically sprayed on the dorsal skin of the mice once a day for 16 days. Medical threads were embedded into the dorsal skin of the mice in a single application. Hair growth activity was evaluated by using dermoscopic and microscopic observations. Sections of the dorsal skin were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), fibroblast growth factor-7 (FGF-7), and fibroblast growth factor-5 (FGF-5) were detected by using immunohistochemical staining. A reverse transcription-polymerase chain reaction (RT-PCR) analysis was adopted to measure the messenger RNA (mRNA) expressions of FGF-7 and FGF-5. Results: TET enhanced anagen development in the hair follicles of C57BL/6 mice. The expressions of BrdU and PCNA, both of which imply active cellular proliferation, were increased by using TET. Moreover, TET increased the expression of FGF-7, an anagen-inducing growth factor, while decreasing the expression of FGF-5, an anagen-cessation growth factor, both at the protein and the mRNA levels. Conclusion: TET enhanced hair re-growth in C57BL/6 mice. TET regulated the expressions of anagen-associated growth factors and activated the proliferation of hair follicular cells in depilated skin lesions. Considering its long-lasting effect, TET may be a good alternative therapeutic for the treatment of alopecia.

• 대한한의학회지
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• 제30권5호
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• pp.50-60
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• 2009

Objectives: To elucidate the antitumor activities of Hang-Am-Dan (HAD), we investigated the anti-proliferative effects and related mechanisms of HAD, the main ingredients such as Cordyceps Militaris and Santisigu Tuber, and its main effective components cordycepin and colchicin, respectively. Methods: We cultivated Calu6 and MCF-7 cells and gave them phosphate-buffered saline extracts of HAD, each ingredient of HAD, and the main effective components of each ingredient. After these processes, we performed MTT assay, BrdU assay, TUNEL assay, SDS-PAGE and Western blot analysis and observed the results. Results: The survival rate of these two cancer cells in HAD were 34-38%. The survival rate in extract of Cordyceps militaris (ECM) and extract of Santisigu tuber (EST) were both about 50%. Cordycepin showed decreased survival rate in both cancer cells, 32% and 89%. Colchicin also showed decreased survival rate, 30% and 16%. We observed that all of the cancer cells got apoptotic bodies after adding the extracts and they have more apoptotic bodies when they were exposed to more extracts. The expression of caspase-3 was increased in Calu6 cell lines treated with the ECM, cordycepin and colchicin. The expression of p53 and p21 were increased in the MCF-7 cell lines treated with the ECM and cordycepin. Conclusions: HAD showed cytotoxic activities on the two kinds of human cancer cell lines, Calu6 and MCF-7. Additionally, HAD and its main ingredients caused a dose-dependent inhibition of cell proliferation and induced the apoptotic cell death.