• Molecules and Cells
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• 제42권5호
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• pp.397-405
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• 2019

The regulatory role of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in both cancerous and noncancerous cells have been widely reported. This study aimed to evaluate the role of lncRNA GAS5 in heart failure caused by myocardial infarction. We reported that silence of lncRNA GAS5 attenuated hypoxia-triggered cell death, as cell viability was increased and apoptosis rate was decreased. This phenomenon was coupled with the down-regulated expression of p53, Bax and cleaved caspase-3, as well as the up-regulated expression of CyclinD1, CDK4 and Bcl-2. At the meantime, the expression of four heart failure-related miR-NAs was altered when lncRNA GAS5 was silenced (miR-21 and miR-142-5p were up-regulated; miR-30b and miR-93 were down-regulated). RNA immunoprecipitation assay results showed that lncRNA GAS5 worked as a molecular sponge for miR-142-5p. More interestingly, the protective actions of lncRNA GAS5 silence on hypoxia-stimulated cells were attenuated by miR-142-5p suppression. Besides, TP53INP1 was a target gene for miR-142-5p. Silence of lncRNA GAS5 promoted the activation of PI3K/AKT and MEK/ERK signaling pathways in a miR-142-5p-dependent manner. Collectively, this study demonstrated that silence of lncRNA GAS5 protected H9c2 cells against hypoxia-induced injury possibly via sponging miR-142-5p, functionally releasing TP53INP1 mRNA transcripts that are normally targeted by miR-142-5p.

• Tuberculosis and Respiratory Diseases
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• 제76권3호
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• pp.114-119
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• 2014

Background: Epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, has anti-cancer activity in human and animal models. We investigated the schedule-dependent effect of EGCG and paclitaxel on growth of NCI-H460 non-small cell lung cancer cells. Methods: To investigate the combined effect of EGCG (E) and paclitaxel (P), combination indices (CIs) were calculated, and cell cycle analysis was performed. For the effect on cell apoptosis, western blot analysis was also performed. Results: CI analysis demonstrated that both concurrent and sequential E ${\rightarrow}$ P treatments had antagonistic effects (CIs >1.0), but sequential P ${\rightarrow}$ E had synergistic effects (CIs <1.0), on the growth inhibition of NCI-H460 cells. In the cell cycle analysis, although paclitaxel induced $G_2/M$ cell cycle arrest and increased the sub-G1 fraction, concurrent EGCG and paclitaxel treatments did not have any additive or synergistic effects compared with the paclitaxel treatment alone. However, western blot analysis demonstrated that sequential P ${\rightarrow}$ E treatment decreased the expression of Bcl-2 and procaspase-3 and increased poly(ADP-ribose) polymerase (PARP) cleavage; while minimal effects were seen with concurrent or sequential E ${\rightarrow}$ P treatments. Conclusion: Concurrent or sequential E ${\rightarrow}$ P treatment had opposite effects to P ${\rightarrow}$ E treatment, where P ${\rightarrow}$ E treatment showed a synergistic effect on growth inhibition of NCI-H460 cells by inducing apoptosis. Thus, the efficacy of EGCG and paclitaxel combination treatment seems to be schedule-dependent.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.175-181
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• 2018

Carbon monoxide (CO) is well-known as toxic gas and intrinsic signaling molecule such as neurotransmitter and blood vessel relaxant. Recently, it has been reported that low concentration of CO exerts therapeutic actions under various pathological conditions including liver failure, heart failure, gastric cancer, and cardiac arrest. However, little has been known about the effect of CO in neurodegenerative diseases like Parkinson's disease (PD). To test whether CO could exert a beneficial action during oxidative cell death in PD, we examined the effects of CO on 6-hydroxydopamine (6-OHDA)-induced cell death in C6 glioma cells. Treatment of CO-releasing molecule-2 (CORM-2) significantly attenuated 6-OHDA-induced apoptotic cell death in a dose-dependent manner. CORM-2 treatment decreased Bax/Bcl2 ratio and caspase-3 activity, which had been increased by 6-OHDA. CORM-2 increased phosphorylation of NF-E2-related factor 2 (Nrf2) which is a transcription factor regulating antioxidant proteins. Subsequently, CORM-2 also increased the expression of heme oxygenase-1 and superoxide dismutases (CuZnSOD and MnSOD), which were antioxidant enzymes regulated by Nrf2. These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.

• Journal of Chest Surgery
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• 제27권6호
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• pp.427-434
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• 1994

A clinical study was designed to evaluate myocardial metabolism during continuous cold blood cardioplegia [Group A, n=10] in comparison with continuous warm blood cardioplegia [Group B, n=10], in a prospective randomized manner. Myocardial metabolism was assessed in two ways: either by collecting blood from coronary sinus before and after cardiopulmonary bypass or by collecting blood from cardioplegic affluent and effluent simultaneously at the beginning and at the end of cardioplegia. The former samples were assayed for gas analysis, lactic acid and cardiac enzyme [CK, LDH, SGOT] and the latter for gas analysis and lactic acid as a maker of anaerobic metabolism. The results were as follows. 1] Myocardial metabolism was shown to be continued in the state of cardioplegia at lower temperature as evidenced by high oxygen extraction of cardioplegic solution in Group A. 2] Anaerobic metabolism occurring at lower temperature in spite of continuous cold blood cardioplegia can be significantly reduced by continuous perfusion of normothermic blood cardioplegics as evidenced by significant reduction of lactate production in Group B [p〈0.05]. 3] Better myocardial protection can be achieved by employing continuous warm blood cardioplegia as evidenced by less cardiac enzyme release in Group B after cardiopulmonary bypass.

• Journal of Chest Surgery
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• 제36권3호
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• pp.123-130
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• 2003

배경: 공압식 심실보조기의 실험을 위한 심부전 모델을 개발하는 데 있어서 사람의 심장구조와 유사하고 저렴하며 일관되게 반복적으로 급성심부전을 유발할 수 있는 방법을 찾기 위해 본 연구진은 사람의 심장구조와 가장 유사하며 저렴한 돼지를 사용하여 관상동맥의 좌전하행지를 결찰하는 방법으로 급성심부전을 유발시키고자 하였다. 대상 및 방법: 성인의 몸무게에 해당하는 5마리의 돼지를 사용하여 전신마취 후 좌측개흉술을 통하여 심장을 노출시키고 관상동맥의 좌전하행지의 원위부에서 시작하여 근위부로 올라오면서 결찰, 재관류, 결찰의 방법으로 심부전을 유발시켰다. 각 과정의 전, 후에 좌심실확장기말기압력, 동맥압, 심박출계수를 측정하였고, 심외막 심에코도를 통하여 좌심실확장기내경, 좌심실수축기내경, 분획단축, 심구혈률을 측정하였다. 이와 같은 과정을 좌전하행지의 원위부부터 근위부까지 충분한 심부전이 달성될 때까지 반복하였으며 목표달성 후 심실보조기를 장착하여 구동시켰다. 결과: 5마리 중 3마리에서 안정적인 심부전을 달성할 수 있었으며 3마리 모두에서 심외막 심에코도상 심구혈률을 기준으로 관상동맥 결찰 전에 비하여 50% 정도의 심기능 저하를 유지 할 수 있었다. 또한 결찰, 재관류, 결찰의 방법을 통하여 심근에 대해 허혈성 전처치를 시행한 후 완전 결찰을 시행하였을 때 대동물의 관상동맥 결찰 시 흔히 발생하는 심실성 부정맥이나 심관기절에의한 심정지도 관찰되지 않았으며 병리조직학적 소견상 심근허혈을 유발시킨 좌, 우심실의 심첨부에서 중간부위까지 광범위한 허혈성 손상을 입은 심근세포들을 확인할 수 있었다. 결론: 허혈성 전처치의 개념을 관상동맥 결찰을 통한 심부전 모델에 적용하여 좌전하행지의 원위부에서부터 근위부 까지 순차적으로 결찰, 재관류, 결찰을 시도한 결과 안정적이고 반복 가능한 급성 심부전 모델을 얻을 수 있었다.

• Acute and Critical Care
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• 제33권4호
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• pp.246-251
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• 2018

Background: Target temperature management (TTM) improves neurological outcomes for comatose survivors of out-of-hospital cardiac arrest. We compared the efficacy and safety of a gel pad cooling device (GP) and a water blanket (WB) during TTM. Methods: We performed a retrospective analysis in a single hospital, wherein we measured the time to target temperature ($<34^{\circ}C$) after initiation of cooling to evaluate the effectiveness of the cooling method. The temperature farthest from $33^{\circ}C$ was selected every hour during maintenance. Generalized estimation equation analysis was used to compare the absolute temperature differences from $33^{\circ}C$ during the maintenance period. If the selected temperature was not between $32^{\circ}C$ and $34^{\circ}C$, the hour was considered a deviation from the target. We compared the deviation rates during hypothermia maintenance to evaluate the safety of the different methods. Results: A GP was used for 23 patients among of 53 patients, and a WB was used for the remaining. There was no difference in baseline temperature at the start of cooling between the two patient groups (GP, $35.7^{\circ}C$ vs. WB, $35.6^{\circ}C$; P=0.741). The time to target temperature (134.2 minutes vs. 233.4 minutes, P=0.056) was shorter in the GP patient group. Deviation from maintenance temperature (2.0% vs. 23.7%, P<0.001) occurred significantly more frequently in the WB group. The mean absolute temperature difference from $33^{\circ}C$ during the maintenance period was $0.19^{\circ}C$ (95% confidence interval [CI], $0.17^{\circ}C$ to $0.21^{\circ}C$) in the GP group and $0.76^{\circ}C$ (95% CI, $0.71^{\circ}C$ to $0.80^{\circ}C$) in the WB group. GP significantly decreased this difference by $0.59^{\circ}C$ (95% CI, $0.44^{\circ}C$ to $0.75^{\circ}C$; P<0.001). Conclusions: The GP was superior to the WB for strict temperature control during TTM.

• Journal of Chest Surgery
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• 제25권12호
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• pp.1391-1398
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• 1992

The hypothesis tested is that shifts in pH, induced when a cardioplegic solution is oxygenated, can be detrimental. The object of this study is to evaluate the effect of the pH of the oxygenating cardioplegic solution on postischemic recovery in the isolated rat heart. Either 100% oxygen or 95% oxygen: 5% carbon dioxide was added to the cardioplegic solution[St. Thomas` Hospital No. 2] and determined postischemic recovery of isolated rat hearts after 2 hours and 3 hours of 20oC cardioplegic protected ischemia. Heart were arrested and reinfused every 30 minutes throughout the ischemic period with cardioplegic solution. When 100% oxygen was added, the pH of the cardioplegic solution increased from 7.8[no oxygen] to 8.5[100% oxygen] without any change in postischemic functional recovery. But when 95% oxygen ; 5% carbon dioxide was added, the pH of the cardioplegic solution reversely decreased to 6.84 in the 2-hour ischemic group and 6.73 in the 3-hour ischemic group, associated with improved postischemic functional recovery. After 2-hour ischemia, systolic pressure improved from 88.2$\pm$3.7%[no oxygen] and 88.7$\pm$3.8%[100% oxygen] to 96.6$\pm$1.8%[95% oxygen : 5% carbon dioxide], p<0.05, aortic flow from 43.3$\pm$3.1% and 38.4$\pm$10.6% to 74.5$\pm$5.0%, p<0.001, cardiac output from 55.5$\pm$4.6% and 47.4%$\pm$10.6% to 73.1$\pm$4.6%, p<0.05, stroke volume from 62.7$\pm$4.6% and 52.0$\pm$10.1% to 77.2$\pm$4.6%, p<0.05, and dP/dT from 59.3$\pm$7.2% and 56.7$\pm$7.6% to 78.9$\pm$4.6%, p<0.05. The infused amount of the cardioplegic solution during 2-hour ischemic period was similar in three groups. After 3-hour ischemia, cardiac output improved from 17.0$\pm$3.8%[no oxygen] to 45.9$\pm$7.5%[95% oxygen: 5% carbon dioxide], p<0.05, and stroke volume from 21.0$\pm$3.9%[no oxygen] to 50.1$\pm$6.6%[95% oxygen: 5% carbon dioxide], p<0.01. In conclusion, the St. Thomas` Hospital No. 2 cardioplegic solution should be oxygenated but with 95% oxygen: 5% carbon dioxide and not 100% oxygen because of the additive effect of a relatively "Acidotic" pH.t; pH.

• 생약학회지
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• 제33권2호통권129호
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• pp.130-136
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• 2002

Melanogenesis is a physiological process resulting in the synthesis of melanin pigments, which play a crucial protective role against skin photocarcinogenesis. The heart wood of Caesalpinia sappan L.(C. sappan) has long been commonly used in Oriental folk medicines to promote blood circulation, and as an emmenagogue, analgesic or anti-inflammatory agent as well as a remedy for thrombosis. From the heartwood, many constituents have been purified and among them, brazilin and hematoxylin are two of the most abundant. This present study was designed to investigate the inhibitory effect of butanol extract from C. sappan on proliferation and melanogenesis in Melan-a cells. After 48 h treatment of these cells with various concentrations of butanol extract, the cells showed a dose-dependent inhibition in their proliferation without apoptotic cell death. Therefore, the growth retardation by the extract may be due to the cell arrest or cell differentiation. We also estimated total melanin content as a final product and activity of tyrosinase, a key enzyme, of melanogenesis in Melan-a cells. The melanin content and tyrosinase activity were deσeased in extract-treated cells in a dose dependent manner compared to control group. The butanol extract also resulted in a decrease of melanin content in ${\alpha}-melanocyte-stimulating$ hormone (MSH)-induced melanogenesis, indicating that butanol extract of C. sappan could be developed as skin whitening components of cosmetics.

• Journal of Chest Surgery
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• 제34권10호
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• pp.792-796
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• 2001

만성 폐동맥 색전증은 비교적 드문 질환으로 저산소증과 폐동맥 고혈압을 일으켜 결국 호흡부전 및 우심부전을 초래한다. 급성 폐동맥 색전증 환자들은 대부분 혈전 방지제, 혈전용해제 등의 내과적 치료에 잘 치료되나 만성 폐동맥 색전증의 경우 섬유화된 혈전이 폐동맥벽에 견고히 붙어있어 내과적 치료에는 별 효과가 없어, 수술적 치료를 고려할 수 있겠다. 본원에서는 만성 폐쇄성 폐질환 및 만성 폐동맥 색전증으로 진단 받고 타 병원에서 수 차례 입원 치료를 받아 오던 47세 남자환자를 간헐적인 완전 순환 정지를 이용하여 폐색전증에 대한 내막 절제술을 시행하여 좋은 결과를 얻었기에 보고하는 바이다

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.616-624
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• 2022

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC₅₀ of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC₅₀ of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.