• Reproductive and Developmental Biology
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• v.37 no.2
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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.

• Journal of Life Science
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• v.12 no.1
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• pp.55-60
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• 2002

The differentiation of skeletal muscle precursor cells in culture is marked by the transcriptional activation of muscle-specific genes and the morphological differentiation of myoblast into multinucleate myotube. In this study, we examined the effect of TSA (Trichostatin A) on WF-kB DNA binding activity and muscle cell fusion in the process of myogenesis. Under TSA treatment, C2C12 myoblast could not fuse to myotube and its NF-kB DNA binding activity was also blocked. To investigate whether these phenomenons were affected by TSA in direct or not, differentiation media (DM) used to differentiate cells without TSA was concentrated and added to C2C12 myoblast with TSA simultaneously. C2C12 myoblast was fused to myotube and NF-kB DNA binding activity was recovered. These results suggest that TSA affects on the differentiation of myoblast, perhaps through several factors, by inhibiting myoblst fusion and blocking NF-kB DNA binding activity.

• Clinics in Shoulder and Elbow
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• v.26 no.1
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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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• v.25 no.1
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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.

• Journal of Life Science
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• v.15 no.5 s.72
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• pp.726-733
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• 2005

Histone deacetylase (HDAC) inhibitors target key steps of tumor development. They inhibit proliferation, induce differentiation and/or apoptotic cell death, and exhibit potent antimetastatic and antiangiogenic properties in cancer cells in vitro and in vivo. Although they are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. The present study was undertaken to investiate the underlying mechanism of a HDAC inhibitor trichostatin A (TSA)-induced growth arrest and its effect on the cell cycle control gene products in a human lung carcinoma cell line A549. TSA treaoent induced the growth inhibition and morphological changes in a concentration-dependent manner. Treatment of A549 cells with TSA resulted in a concentration-dependent increased G1 (under 100 ng/ml) and/or G2/M (200 ng/ml) cell population of the cell cycle as determined by flow cytometry Moreover, 200 ng/ml TSA treatment significantly induced the population of sub-G1 cells (23.0 fold of control). This anti-proliferative effect of TSA was accompanied by a marked inhibition of cyclins, positive regulators of cell cycle progression, and cyclin-dependent kinases (Cdks) expression and concomitant induction of tumor suppressor p53 and Cdk inhibitors such as p21 and p27 Although further studies are needed, these findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of TSA in human lung carcinoma cells.

• Journal of Life Science
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• v.18 no.3
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• pp.336-343
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• 2008

Histone deacetylases (HDACs) inhibitors have emerged as the accessory therapeutic agents for various human cancers, since they can block the activity of specific HDACs, restore the expression of some tumor suppressor genes and induce cell differentiation, cell cycle arrest and apoptosis in vitro and in vivo. In the present study, we investigated that the effect of trichostatin A (TSA), an HDAC inhibitor, on the cell growth and apoptosis, and its effect on the nuclear factor-kappaB $(NF-{\kappa}B)$ activity in 267B1 human prostate epithelial cells. Exposure of 267B1 cells to TSA resulted in growth inhibition and apoptosis induction in and dose-dependent manners as measured by fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. TSA treatment inhibited the levels of IAP family members such as c-IAP-1 and c-IAP-2 and induced the proteolytic activation of caspase-3, -8 and -9, which were associated with concomitant degradation of poly (ADP-ribose)-polymerase, ${\beta}-catenin$ and laminin B proteins. The increase in apoptosis by TSA was connected with the translocation of $NF-{\kappa}B$ from cytosol to nucleus, increase of the DNA binding as well as promoter activity of $NF-{\kappa}B$, and degradation of cytosolic inhibitor of KappaB $(I{\kappa}B)-{\alpha}$ protein. We therefore concluded that TSA demonstrated anti-proliferative and apoptosis-inducing effects on 267B1 cells in vitro, and that the activation of caspases and $NF-{\kappa}B$ may play important roles in its mechanism of action. Although further studies are needed, these findings provided important insights into the possible molecular mechanisms of the anti-cancer activity of TSA.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.11
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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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• v.37 no.1
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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.

• Microbiology and Biotechnology Letters
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• v.45 no.1
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• pp.81-86
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• 2017

Alignment of 967 reference sequences of the typical 2-Cys peroxiredoxin family of proteins revealed that 10 amino acids were conserved, with over 99% identity. To investigate whether the conserved aspartic acid residues and serine residue affect the peroxidase and chaperone activity of the protein, we prepared yeast TSA1 mutant proteins in which aspartic acids at positions 75 and 103 were replaced by valine or asparagine, and serine at position 73 was replaced by alanine. By non-reducing SDS-PAGE, TSA1 and the S73A, D75V and D75N mutants were detected in dimeric form, whereas the D103V and D103N mutants were detected in various forms, ranging from high molecular-weight to monomeric. Compared with wild type TSA1, the D75N mutant exhibited 50% thioredoxin peroxidase activity, and the S73A and D75V mutants showed 25% activity. However, the D103V and D103N mutants showed no peroxidase activity. All proteins, except for the D103V and D103N mutants, exhibited chaperone activity at $43^{\circ}C$. Our results suggest that the two conserved aspartic acid residues and serine residue of TSA1 play important roles in its thioredoxin peroxidase activity, and D103 plays a critical role in its chaperone activity.

• Bulletin of the Korean Chemical Society
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• v.10 no.1
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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.