• Title/Summary/Keyword: MCL1

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Telomerase Reverse Transcriptase Contains a BH3-Like Motif and Interacts with BCL-2 Family Members

  • Jin, Young;You, Long;Kim, Hye Jeong;Lee, Han-Woong
    • Molecules and Cells
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    • v.41 no.7
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    • pp.684-694
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    • 2018
  • Upregulation of human telomerase reverse transcriptase (hTERT) expression is an important factor in the cellular survival and cancer. Although growing evidence suggests that hTERT inhibits cellular apoptosis by telomere-independent functions, the mechanisms involved are not fully understood. Here, we show that hTERT contains a BH3-like motif, a short peptide sequence found in BCL-2 family proteins, and interacts with anti-apoptotic BCL-2 family proteins MCL-1 and BCL-xL, suggesting a functional link between hTERT and the mitochondrial pathway of apoptosis. Additionally, we propose that hTERT can be categorized into the atypical BH3-only proteins that promote cellular survival, possibly due to the non-canonical interaction between hTERT and antiapoptotic proteins. Although the detailed mechanisms underlying the hTERT BH3-like motif functions and interactions between hTERT and BCL-2 family proteins have not been elucidated, this work proposes a possible connection between hTERT and BCL-2 family members and reconsiders the role of the BH3-like motif as an interaction motif.

Numerical Analysis and Experimental Measurement of Hygroscopic Warping Effects for Cellulose Fibres (셀룰로스 복합소재에서의 수분에 의한 뒤틀림 변형효과를 위한 수치해석적 실험적 연구)

  • Kim, Byeong-Sam;Kim, Ki-Jun
    • Journal of the Korean Society of Safety
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    • v.19 no.1
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    • pp.117-123
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    • 2004
  • The prediction to the hydroscopic moisture warping behaviors is analyzed for cellulose-based laminates using a numerical method base on a modified classical laminate(MCL) theory for hygroscopic moisture deformations with cycling testing data. The experimental measurement of the interferometric hygroscopic warping effects, moisture generator, and curvature of cellulose reinforced epoxy laminates is studied under cyclic environmental conditions using a Moire interferometer coupled. Accurate determination of curvatures provides a description of dimensional stability evolution; the tools for validation of computational internal stress and for the warpage prediction in model safety.

A Case Report of Yeoldahanso-tang on Sudden Hearing Loss and Tinnitus after Trigeminal Schwannoma Surgery (열다한소탕의 삼차신경초종 수술후 돌발성 난청 및 이명 치험 1례)

  • Kang, Yu-Jeong;Ha, Dong-Lim;Yeum, Jiyoon;Oh, Seungyun
    • Journal of Sasang Constitutional Medicine
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    • v.33 no.4
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    • pp.23-31
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    • 2021
  • Objective The case report showed that sudden hearing loss and tinnitus after trigeminal schwannoma surgery were improved with Yeoldahansotang-gamibang. Method The patient was diagnosed with Taeeumin interior heat (Ganyeol) disease based on the original symptoms of Taeeumin. He was treated with herbal medicine and acupuncture treatment. Puretone audiometry (PTA), speech audiometry, tinnitus handicap inventory (THI) and the original symptoms were investigated before and after the treatment. Results Right side PTA score was significantly reduced, speech audiometry was improved in speech reception threshold (SRT), word recognition score (WRS) and most comfortable level (MCL) and THI score decreased from 40 to 0, which showed normalizing hearing function. And the patient revealed improvements in sleeping, digestion, stooling, perspiration and facial sensation after treatment. Conclusion This study suggests that Yeoldahansotang-gamibang is effective on sudden hearing loss and tinnitus after surgery by correcting the imbalanced energy of Taeeumin.

Leishmania Vaccines: the Current Situation with Its Promising Aspect for the Future

  • Rasit Dinc
    • Parasites, Hosts and Diseases
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    • v.60 no.6
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    • pp.379-391
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    • 2022
  • Leishmaniasis is a serious parasitic disease caused by Leishmania spp. transmitted through sandfly bites. This disease is a major public health concern worldwide. It can occur in 3 different clinical forms: cutaneous, mucocutaneous, and visceral leishmaniasis (CL, MCL, and VL, respectively), caused by different Leishmania spp. Currently, licensed vaccines are unavailable for the treatment of human leishmaniasis. The treatment and prevention of this disease rely mainly on chemotherapeutics, which are highly toxic and have an increasing resistance problem. The development of a safe, effective, and affordable vaccine for all forms of vector-borne disease is urgently needed to block transmission of the parasite between the host and vector. Immunological mechanisms in the pathogenesis of leishmaniasis are complex. IL-12-driven Th1-type immune response plays a crucial role in host protection. The essential purpose of vaccination is to establish a protective immune response. To date, numerous vaccine studies have been conducted using live/attenuated/killed parasites, fractionated parasites, subunits, recombinant or DNA technology, delivery systems, and chimeric peptides. Most of these studies were limited to animals. In addition, standardization has not been achieved in these studies due to the differences in the virulence dynamics of the Leishmania spp. and the feasibility of the adjuvants. More studies are needed to develop a safe and effective vaccine, which is the most promising approach against Leishmania infection.

Hesperidin Induces Apoptosis by Inhibiting Sp1 and Its Regulatory Protein in MSTO-211H Cells

  • Lee, Kyung-Ae;Lee, Sang-Han;Lee, Yong-Jin;Baeg, Seung-Mi;Shim, Jung-Hyun
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.273-279
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    • 2012
  • Hesperidin, a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-tumor activity and apoptotic effects in several cancers, but there is no report about the apoptotic effect of hesperidin in human malignant pleural mesothelioma through the specificity protein 1 (Sp1) protein. We investigated whether hesperidin inhibited cell growth and regulated Sp1 target proteins by suppressing the levels of Sp1 protein in MSTO-211H cells. The $IC_{50}$ value of hesperidin was determined to be 152.3 ${\mu}M$ in MSTO-211H cells for 48 h. Our results suggested that hesperidin (0-160 ${\mu}M$) decreased cell viability, and induced apoptotic cell death. Hesperidin increased Sub-$G_1$ population in MSTO-211H cells. Hesperidin significantly suppressed mRNA/protein level of Sp1 and modulated the expression level of the Sp1 regulatory protein such as p27, p21, cyclin D1, Mcl-1, and survivin in mesothelioma cells. Also, hesperidin induced apoptotic signaling including: cleavages of Bid, caspase-3, and PARP, upregulation of Bax, and down-regulation of Bcl-$_{xl}$ in mesothelioma cells. These results show that hesperidin suppressed mesothelioma cell growth through inhibition of Sp1. In this study, we demonstrated that Sp1 acts as a novel molecular target of hesperidin in human malignant pleural mesothelioma.

Hydrogeochemical Characteristics and Natural Radionuclides in Groundwater for Drinking-water Supply in Korea (국내 음용지하수의 수리지화학 및 자연방사성물질 환경 특성)

  • Jeong, Do-Hwan;Kim, Moon-Su;Lee, Young-Joon
    • Journal of Soil and Groundwater Environment
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    • v.16 no.6
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    • pp.133-142
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    • 2011
  • A total of 247 samples were collected from groundwater being used for drinking-water supply, and hydrogeochemistry and radionuclide analysis were performed. In-situ analysis of groundwaters resulted in ranges of $13.7{\sim}25.1^{\circ}C$ for temperature, 5.9~8.5 for pH, 33~591 mV for Eh, $66{\sim}820{\mu}S/cm$ for EC, and 0.2~9.4 mg/L for DO. Major cation and anion concentrations of groundwaters were in ranges of 0.5~227.6 for Na, 1.0~279.3 for Ca, 0.0~9.3 for K, 0.1~100.1 for Mg, 0.0~3.3 for F, 0.9~779.1 for Cl, 0.3~120.4 for $SO_4$, 0.0~27.4 for $NO_3$-N, and 6~372 mg/L for $HCO_3$. Uranium-238 and radon-222 concentrations were detected in ranges of N.D-$131.1{\mu}g/L$ and 18-15,953 pCi/L, respectively. In case of some groundwaters exceeding USEPA MCL level ($30{\mu}g/L$) for uranium concentration, their pH ranged from 6.8 to 8.0 and Eh showed a relatively low value(86~199 mV) compared to other areas. Most groundwaters belonged to Ca-(Na)-$HCO_3$ type, and groundwaters of metamorphic rock exhibited the highest concentration of Na, Mg, Ca, Cl, $NO_3$-N, U, and those of plutonic rock showed the highest concentration of $HCO_3$, and Rn. Uranium and fluoride from granite areas did not show any correlation. However, uranium and bicarbonate displayed a positive relation of some areas in plutonic rocks($R^2$=0.3896).

Protective Effects of Oleic Acid Against Palmitic Acid-Induced Apoptosis in Pancreatic AR42J Cells and Its Mechanisms

  • Ahn, Joung Hoon;Kim, Min Hye;Kwon, Hyung Joo;Choi, Soo Young;Kwon, Hyeok Yil
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.1
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    • pp.43-50
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    • 2013
  • Palmitic acid (PAM), one of the most common saturated fatty acid (SFA) in animals and plants, has been shown to induce apoptosis in exocrine pancreatic AR42J cells. In this study, we investigated cellular mechanisms underlying protective effects of oleic acid (OLA) against the lipotoxic actions of PAM in AR42J cells. Exposure of cells to long-chain SFA induced apoptotic cell death determined by MTT cell viability assay and Hoechst staining. Co-treatment of OLA with PAM markedly protected cells against PAM-induced apoptosis. OLA significantly attenuated the PAM-induced increase in the levels of pro-apoptotic Bak protein, cleaved forms of apoptotic proteins (caspase-3, PARP). On the contrary, OLA restored the decreased levels of anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-xL, and Mcl-1) in PAM-treated cells. OLA also induced up-regulation of the mRNA expression of Dgat2 and Cpt1 genes which are involved in triacylglycerol (TAG) synthesis and mitochondrial ${\beta}$-oxidation, respectively. Intracellular TAG accumulation was increased by OLA supplementation in accordance with enhanced expression of Dgat2 gene. These results indicate that restoration of anti-apoptotic/pro-apop-totic protein balance from apoptosis toward cell survival is involved in the cytoprotective effects of OLA against PAM-induced apoptosis in pancreatic AR42J cells. In addition, OLA-induced increase in TAG accumulation and up-regulation of Dgat2 and Cpt1 gene expressions may be possibly associated in part with the ability of OLA to protect cells from deleterious actions of PAM.

Study on Anti-Cancer Effects of Rhus Verniciflua Stokes Extracted with Sterile Distilled Water on Two Cholangiocarcinoma Cell Lines, SNU-1079 and SNU-1196 (칠피(漆皮) 추출물의 담도암 세포주 SNU-1079와 SNU-1196에 대한 항암효과)

  • Joung, Bo-bae;Kim, Young-chul
    • The Journal of Internal Korean Medicine
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    • v.36 no.1
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    • pp.1-12
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    • 2015
  • Objectives : This study was performed to investigate the anti-cancer effects of Rhus verniciflua Stokes (RVS) extracted with sterile distilled water on cholangiocarcinoma cell lines. Materials and Methods : Two cholangiocarcinoma cell lines, SNU-1079 and SNU-1196, were used in this study. Cells were treated with different concentrations of RVS for 24, 48, and 72 hours. Cell count, viability, apoptosis, and mRNA expression of Bax, Bcl-2, Mcl-1, survivin, caspase-3, and cyclin D1 and P21 were determined with an automatic cell counter (ADAM-MC), MTT assay, apoptosis assay (Annexin-V/PI staining), and RT-PCR. Results : All cells treated with RVS showed decreased cell counts in a dose-dependent manner. RVS inhibited proliferation of SNU-1196 in a dose-dependent manner, but SNU-1079 proliferation was inhibited in the long-time culture group in a dose-dependent manner. The proportion of early and late-stage apoptotic cells was increased by RVS in a dose-dependent manner in SNU-1196. In contrast, it was increased significantly in SNU-1079 treated with high-dose RVS. After treatment with RVS, the mRNA expression of Bcl-2 was decreased while Bax was increased in SNU-1079. Cyclin D1 mRNA levels were decreased in SNU-1196 in a dose-dependent manner. P21 expression was increased in all cells after the treatment with RVS. Conclusions : RVS appears to have potential as a therapeutic agent for cholangiocarcinoma.

Study of the Length of Needle Thoracostomy Catheter Needed for Patients with Chest Trauma (흉부 외상 환자에서 늑막 천자를 위해 바늘 도관의 길이에 대한 연구)

  • Kang, Sung Won;Ryoo, Hyun Wook;Park, Jung Bae;Seo, Kang Suk;Chung, Jae Myung
    • Journal of Trauma and Injury
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    • v.22 no.1
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    • pp.1-4
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    • 2009
  • Purpose: This study was conducted to evaluate the length of the catheter used in a needle thoracostomy for emergency decompression of a tension pneumothorax by measuring the chest wall thickness (CWT) in patients with chest trauma Methods: A retrospective review of 201 patients with chest trauma who had been transported the emergency department in a tertiary university hospital in a metropolitan area between 1 January and 31 February 2007 was performed. The average CWT at the second intercostal space (ICS) in the midclavicular line (MCL) was measured by using a chest computed tomography scan. Results: As the left and the right mean CWTs were $3.4{\pm}1.0cm$ and $3.4{\pm}1.0cm$, respectively, there was no significant statistical difference between them. The mean CWT of female patients was significantly higher than that of male patients (p=0.001). The mean CWT of patients under the age of 65 years was significantly thicker than that of the patients over the age of 65 years (p<0.001). Of the studied patients, 12 (6.0%) a CWT > 5 cm. Conclusion: A 5 cm-length catheter in a needle thoracostomy may be insufficient for emergency decompression of a tension pneumothorax, so a catheter longer than 5 cm in length is needed.

IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway

  • Young-Ju Kang;Hee Jun Cho;Yunhee Lee;Arum Park;Mi Jeong Kim;In Cheul Jeung;Yong-Wook Jung;Haiyoung Jung;Inpyo Choi;Hee Gu Lee;Suk Ran Yoon
    • IMMUNE NETWORK
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    • v.23 no.2
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    • pp.14.1-14.14
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    • 2023
  • Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.