• Reproductive and Developmental Biology
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• 제37권2호
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• pp.57-64
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• 2013

Developmental potential of cloned embryos is related closely to epigenetic modification of somatic cell genome. The present study was to investigate the effects of applying histone deacetylation inhibitor, trichostatin A (TSA) to activated porcine embryos on subsequent development of porcine parthenogenetic and nuclear transfer embryos. Electrically activated oocytes were treated with 5 nM TSA for different exposure times (0, 1, 2 and 4 hr) and then the activated embryos were cultured for 7 days. The reconstructed embryos were treated with different concentrations of 0, 5, 10 and 25 nM TSA for 1 hr. Also 5 nM TSA was tested with different exposure times of 0, 0.5, 1, 2 and 4 hr. And fetal fibroblast cells were treated with 50 nM TSA for 1, 2 or 4 hr and with 5 nM TSA for 1 hr. Cumulus-free oocytes were enucleated and reconstructed by TSA-treated donor cells and electrically fused and cultured for 6 days. In parthenogenetic activation experiments, 5 nM TSA treatment for 1 hr significantly improved the percentage of blastocyst developmental rates than the other groups. Total cell number of blastocysts in 1 hr group was significantly higher than other groups or control. Similarly, blastocyst developmental rates of porcine NT embryos following 5 nM TSA treatment for 1 hr were highest. And the reconstructed embryos from donor cells treated by 50 nM TSA for 1 hr improved the percentage of blastocyst developmental rates than the control group. In conclusion, TSA treatment could improve the subsequent blastocyst development of porcine parthenogenetic and nuclear transfer embryos.

• 생명과학회지
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• 제12권1호
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• pp.55-60
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• 2002

골격근 세포의 분화는 근육특이 유전자들의 전사적 활성과 근육아세포에서 근육소관으로의 형태적 분화로 특징지어진다. 본 연구에서는 TSA가 근육형성의 일련의 과정에서 NF-kB DNA 결합 활성과 융합에 미치는 영향을 조사하였다. 대조군과 비교해서 TSA가 처리된 C2C12 myoblast는 융합하여 근육소관을 형성할 수 없었으며 NF-kB DNA 결합 활성은 억제되었다. 이런 현상들이 TSA에 의한 직접적인 것인지 알아보기 위해서 TSA가 처리되지 않고 분화를 유도하기 위해서 사용된 배지를 농축하여 C2C12 myoblast에 TSA와 함께 동시에 처리하였다. 그 결과 세포는 융합하여 근육소관을 형성하였으며 NF-kB DNA 결합 활성이 회복되었다. 이러한 결과는 TSA가 아마도 여러 관련 인자들을 통해 myoblast의 융합과 NF-kB DNA 결합 활성을 억제함으로 근육형성과정에 영향을 미침을 시사한다.

• Clinics in Shoulder and Elbow
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• 제26권1호
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• pp.32-40
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• 2023

Background: The purpose of this study was to identify predictors of the time from initial presentation to total shoulder arthroplasty (TSA) in patients with primary glenohumeral osteoarthritis (OA) and rotator cuff (RTC) arthropathy who were conservatively managed with corticosteroid injections. Methods: We conducted a retrospective cohort study of patients who underwent TSA from 2010 to 2021. Kaplan-Meier survival analysis was used to estimate median time to TSA for primary OA and RTC arthropathy patients. The Cox proportional hazards model was used to identify significant predictors of time to TSA and to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical significance was set at P<0.05. Results: The cohort included 160 patients with primary OA and 92 with RTC arthropathy. In the primary OA group, median time to TSA was 15 months. Significant predictors of shorter time to TSA were older age at presentation (HR, 1.02; 95% CI, 1.00-1.04; P=0.03) and presence of moderate or severe acromioclavicular joint arthritis (HR, 1.45; 95% CI, 1.05-2.01; P=0.03). In the RTC arthropathy group, median time to TSA was 14 months, and increased number of corticosteroid injections was associated with longer time to TSA (HR, 0.87; 95% CI, 0.80-0.95; P=0.003). Conclusions: There are distinct prognostic factors for progression to TSA between primary OA patients and RTC arthropathy patients managed with corticosteroid injections. Multiple corticosteroid injections are associated with delayed time to TSA in RTC arthropathy patients.

• Clinics in Shoulder and Elbow
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• 제25권1호
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• pp.42-48
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• 2022

Background: Total shoulder arthroplasty (TSA) has been demonstrated to be an effective treatment for multiple shoulder pathologies. The purpose of our study was to compare the relative value units (RVUs) per minute of surgical time for primary and revision TSA. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients that underwent primary TSA, one-component revision TSA, and two-component revision TSA between January 1, 2015 and December 31, 2017 using current procedure terminology codes. RVUs were divided by mean operative time for each procedure to determine the amount of revenue generated per minute. Rates were compared between the groups using a one-way analysis of variance with post-hoc Tukey test. Statistical significance was set at p<0.05. Results: When dividing compensation by surgical time, we found that two-component revision generated more compensation per minute compared to primary TSA (0.284±0.114 vs. 0.239±0.278 RVU per minute or $10.25±$4.11 vs. $8.64±$10.05 per minute, respectively; p=0.001). Conclusions: The relative value of revision TSA procedures is weighted to account for the increased technical challenges and time associated with these procedures. This study confirms that reimbursement is higher for revision TSA compared to primary TSA.

• 생명과학회지
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• 제15권5호
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• pp.726-733
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• 2005

Histone deacetylase (HDAC) 억제제가 새로운 항암치료제 후보물질로서 유용성이 높은 것으로 평가되지만, 아직까지 인체폐암세포에 관한 연구는 상대적으로 미미한 실정이다. 따라서 본 연구에서는 폐암세포에 미치는 HDAC 억제제의 항암작용 기전을 조사하기 위하여 A549 인체폐암세포주를 대상으로 암세포의 증식에 미치는 대표적인 HDAC 억제제인 tichostatin A (TSA)에 의한 영향을 세포주기 조절관련인자 중심으로 조사하였다. TSA의 처리에 의하여 A549 폐암세포의 증식은 처리 농도 의존적으로 억제되었으며, 심한 형태적 변형을 동반하였다. 저농도 처리군에서는 TSA 농도가 증가할수록 세포주기 G1기의 빈도가 증가하였으나, 고농도 처리군에서는 G2/M기에 속하는 세포의 빈도가 증가되었다. 또한 apoptosis 유발의 간접적인 지표가 되는 sub-G1기에 속하는 세포의 빈도 역시 TSA 처리 농도 의존적으로 매우 증가되었다. 이러한 TSA의 A549 폐암세포 증식억제 효과는 cyclins 및 CdkS의 발현 억제, 종양억제유전자인 p53 및 Cdks 억제제인 p21과 p27의 발현 증가와도 연관성이 있었다. TSA의 항암 기전을 규명하기 위해서는 더 많은 연구가 부가적으로 필요하겠지만, 본 연구의 결과들에 의하면 TSA는 강력한 인체폐암세포의 증식 억제 및 항암작용이 있음을 시사하여 준다고 할 수 있다.

• 생명과학회지
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• 제18권3호
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• pp.336-343
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• 2008

본 연구에서는 인체전립선 상피세포인 267B1 세포에서 HDAC 저해제인 TSA에 의한 증식억제가 apoptosis 유도에 의한 것임을 제시하였다. 이러한 TSA에 의한 267B1 세포의 apoptosis에는 c-IAP-1 및 c-IAP-2와 같은 IAP family의 발현감소가 동반되었으나 Bax 및 Bcl-2와 같은 Bcl-2 family의 발현에는 큰 변화가 없었다. 그리고 TSA에 의한 267Bl 세포의 apoptosis는 caspase의 활성에 의한 표적 단백질들의 분해와 연관성이 있었다. 또한 TSA에 의한 apoptosis 유도에서 $NF-{\kappa}B$의 활성이 증가된다는 것을 세포질에서 $NF-{\kappa}B$의 핵 내로의 이동에 따른 전사활성의 증가 현상에 의한 것임을 다양한 방법으로 제시하였다. 본 연구의 결과는 TSA와 같은 HDAC 저해제에 의한 apoptosis 유도에는 $NF-{\kappa}B$의 활성 증가가 동반될 수 있음을 보여주는 결과로서 HDAC 저해제의 항암활성에 대한 $NF-{\kappa}B$의 새로운 역할 가능성을 제시하여 주는 것으로서 이에 관한 추가적인 연구의 필요성을 제시하였다.

• Asian-Australasian Journal of Animal Sciences
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• 제26권11호
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• pp.1545-1552
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• 2013

This study was conducted to investigate the effects of Trichostatin A (TSA) on cumulus expansion during mouse oocyte maturation. TSA treatment inhibited cumulus expansion and significantly reduced the cumulus expansion index (CEI) (p<0.05). To determine the underlying mechanism, the expression levels of several key factors that play crucial roles in cumulus expansion including components of extracellular matrix (ECM) (Has2, Ptgs2, Ptx3, and Tnfaip6) and Growth differentiation factor 9 (GDF9) were measured in control and TSA treated samples by real-time PCR. The effect of TSA on ERK phosphorylation (p-ERK1/2) in cumulus cells and GDF9 protein level in fully grown oocytes (FGOs) were detected by Western blotting. The expression levels of the ECM genes were significantly decreased (p<0.05) by TSA treatment while GDF9 expression did not response to TSA (p>0.05). TSA treatment blocked the activation of ERK1/2 (p<0.05) and had no significant effect on GDF9 protein expression (p>0.05). Collectively, these results suggested that TSA treatment altered ECM gene expression and blocked ERK1/2 activation to inhibit cumulus expansion in the mouse.

• Journal of Korean Neurosurgical Society
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• 제37권1호
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• pp.16-19
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• 2005

Objective: This study is designed to evaluate the clinical outcome, the safety and the effectiveness of the open sella methods(OSM) with intentionally staged transsphenoidal approach(TSA) for giant pituitary adenomas(GPA). Methods: Eight patients with GPA were managed by the OSM with intentionally staged TSA. There were 5 nonfunctioning adenomas, 2 prolactin-secreting adenomas, and 1 growth hormone-secreting adenoma. Among them, 6 patients underwent two times of TSA, one patient underwent three times of TSA, and the other patient underwent two times of TSA followed by radiation therapy. The mean time interval between staged operations was 3.9 months except for one case. Results: Seven out of the eight patients with GPA treated with the OSM with intentionally staged TSA showed that the tumors were completely removed on magnetic resonance imaging and that they were free from headache and visual problem suffered previously. Only one patient experienced severe complications including panhypo-pituitarism, cerebrospinal fluid rhinorrhea and permanent diabetes insipidus. Conclusion: With the surgical treatment for 8 cases of GPA, which extended to the suprasellar and parasellar area, we suggest that the OSM with intentionally staged TSA is a safe and effective method in management for GPA.

• 한국미생물·생명공학회지
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• 제45권1호
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• pp.81-86
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• 2017

퍼옥시레독신은 티오레독신, 티오레독신 환원효소, NADPH로 이루어진 티오레독신 시스템의 환원력을 이용하여 과산화물을 제거하는 티오레독신 과산화효소 활성과 다른 단백질의 열변성에 의한 응집을 막아주는 샤페론 활성을 갖는 효소이다. 정형 2-Cys Prx군에 속하는 퍼옥시레독신 참고서열 1,024개 중 부분적인 서열 등을 제외한 967개 서열을 정렬하였을 때 75번과 103번 아스파트산 잔기는 99% 보존되었고, 73번 세린 잔기는 97% 보존되었음에도 불구하고 잘 보존된 아스파트산 잔기와 세린 잔기에 대해 알려지지 않았다. 이 잔기가 TSA1의 두가지 효소 활성에 미치는 영향을 알아보기 위해 재조합 단백질을 이용하여 활성도를 알아보았다. in vitro 실험을 통하여 잘 보존된 잔기인 103번 아스파트산은 75번 아스파트산보다 티오레독신 퍼옥시레독신 활성 및 분자 샤페론 활성에 더 영향을 미치고, 103번의 음전하는 분자 샤페론 활성에 중요한 역할을 하며 과산화효소활성에는 75번과 103번의 음전하가 관여함을 알 수 있었다. 또한 73의 세린 잔기 역시 과산화효소에 영향을 미치는 잔기임을 알 수 있었다. 최근 출아 효모 퍼옥시레독신인 TSA2의 79번과 109번의 세린 잔기를 시스테인 잔기로 변이시킨 경우 두 변이 단백질 모두 과산화효소 활성과 샤페론 활성이 증가되었는데 이는 ${\beta}$-sheet 구조의 증가와 관련되는 것으로 보고하였다[28]. 이들 두 세린 잔기는 TSA1 구조에 의하면 모두 ${\alpha}$-나선 구조에 위치하였다. 반면에 73번의 세린 잔기는 ${\beta}$-sheet의 C-말단에 위치하는 잔기로 과산화효소 활성에 대한 영향이 다르게 나타나는 것으로 추정된다. 추후 생체 내 실험을 통하여 아스파트산 잔기의 변이가 과산화물 저항성이 미치는 영향 및 열 저항성(thermal stress)에 미치는 역할을 살펴볼 필요가 있다. 또한 아스파트산 잔기와 과산화물과의 반응 및 분자 샤페론과의 반응에 장애가 되는 요인이 무엇인지에 대한 추가 연구가 필요할 것이다.

• Bulletin of the Korean Chemical Society
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• 제10권1호
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• pp.72-74
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• 1989

Aminolysis of various carboxyl-containing ester substrates by triamines was kinetically studied in dimethyl sulfoxide (DMSO) in the presence of p-toluenesulfonic acid (TSA) or in the presence of sulfuric acid and potassium iodide (KI). In the presence of TSA or KI, the pseudo-first-order rate constants ($k_o$) were proportional to the total amine concentration ($N_o$). This stands in marked contrast with the corresponding reactions carried out with sulfuric acid added as the sole additive, in which saturation kinetic behavior of ko with respect to No was manifested. This indicates that complex formation between the ester substrate and the amine is greatly suppressed by the addition of TSA or KI. The second-order rate constants obtained in the presence of TSA or KI were substantially greater than those measured in the absence of any additive. These kinetic features were explained in terms of tight interaction between the protonated amines with I- or TSA-. Thus, the results were related to the hydrogen bonding that involves DMSO, bisulfate ion, I-, TSA-, and the protonated forms of triamines.