FK506이 T 림프구 사멸에서 활성산소 생성에 미치는 영향

이호균(Ho Kyun Lee),정상영(Sang Young Chung),최수진나(Soo Jin Na Choi) 대한외과학회 2009 Annals of Surgical Treatment and Research(ASRT) Vol.77 No.5

Purpose: Tacrolimus (FK506) has been widely used as an immunosuppressant in organ transplanted recipients to suppress organ rejection phenomenon. We investigated the role of oxidative stress and heme oxygense-1 by FK506 on human Jurkat T cells. Methods: The cells viability was examined by DAPI stain, enzyme activity of caspase family proteins, and western blotting for Baks, PUMA, iNOS, HO-1. Cells were cultured in the absence or presence of CoPPIX or ZnPPIX and the fluorescence intensity was analyzed using a flow cytometry. Results: Treatment with FK506 increased the generation of reactive oxygen species (ROS), including hydrogen peroxide and superoxide anion, and NO in Jurkat cells in a dose-dependent manner. Immunohistochemistry and Western blot analysis data revealed the hemoxygenase-1 (HO-1) was induced by the addition of FK506 in Jurkat cells. Induction of CoPP, HO-1 inducer, resulted in decreased intracellular H₂O₂ and NO concentrations. Instead ZnPP, an HO-1 competitive inhibitor did it reversely. In addition, ZnPP regulates iNOS protein synthesis by inhibition of HO-1. Conclusion: Increase of HO-1 expression would induce to decrease the intracellular H₂O₂ and NO concentrations. Also, HO-1 would regulate iNOS protein synthesis. Consequently, we can expect the regulation of HO-1 expression with concomitants use of FK506 to suppress organ rejection phenomenon by enhancing apoptosis.

Mycophenolic Acid에 의해 유도된 Jurkat 세포주 세포자멸사에서 Heme Oxygenase-1의 발현이 미치는 영향

이호균(Ho Kyun Lee),최수진나(Soo Jin Na Choi) 대한외과학회 2010 Annals of Surgical Treatment and Research(ASRT) Vol.78 No.6

Purpose: This study demonstrates that pharmacologic induction of heme oygenase-1 (HO-1) along with catalytic activation significantly modulated apoptosis of Jurkat cells induced by mycophenolic acid (MPA). Methods: Cells were cultured with the presence or absence of MPA. Flow cytometric analysis was performed after propidium iodide staining. Western blotting of HO-1, Bcl, and Bax was also performed. Cells were stained 4’-6-Diamidino-2-phenylindole (DAPI) and measured by flow cytometry in the absence or presence of CoPPIX. Results: Treatment of MPA decreased cell viability in a dose- and time-dependent manner. MPA-induced cell death was confirmed as apoptosis characterized by sub G0/G1 phase arrest. Expression of HO-1 assumes a pattern of decline after rising at the initial phase. CoPPIX, HO-1 inducer, significantly inhibited the cisplatin-induced apoptosis. Treatment of MPA resulted in reactive oxygen species (ROS) generation in Jurkat cells. CoPPIX attenuated ROS production in MPA-treated cells. Conclusion: This result suggests that the protective mechanism of HO-1 on MPA-induced cytotoxicity is associated with direct inhibition of ROS generation and mitochondrial permeability transition.

鍼刺가 人體의 血漿 Atrial Natriuretic Peptide,Aldosterone, Cortisol 濃度 및 Renin 活性度에 미치는 影響

朴秀雄,李昊燮 圓光大學校 韓醫學硏究所 1991 원광한의학 Vol.1 No.1

The sources of body water are metabolically produced and ingested water. There are four sites from which water is lost to the external environment : skin, lungs, gastrointestinal tract, and kidneys. According to the theory of oriental medicine, the balance of body water is controlled by kidneys, lungs, Bee(脾), urinary bladder, and Sam Cho(三焦), the function of skin is controlled by lungs(肺主皮毛) The aim of the present study was to elucidate the effects of acupuncture in the meridian point Sam Cho Soo(B22), Bee Soo(B20), and Pye Soo(B13) on the renin-angiotensin aldosterone system and atrial natriuretic peptide(ANP). The results obtained were as follows: 1. Plasma atrial natriuretic peptide was decreased significantly after acupuncture in the meridian point Pye Soo(B13) 2. Plasma renin activity was decreased significantly after acupuncture in the meridian point Sam Cho Soo(B22). 3. Plasma renin activity was increased significantly after acupuncture in the meridian point Bee Soo(B20) 4. Plasma aldosterone concentration was decreased significantly after acupuncture in the meridian point Sam Cho Soo(B22) and Bee Soo(B20) 5. Plasma cortisol concentration was decreased significantly after acupuncture in the meridian point Bee Soo(B20). 6. Plasma ACTY concentration was decreased significantly after acupuncture in the meridian points Bee Soo(B20) and Pye Soo(B13) These results suggest that meridian points Sam Cho Soo(B22), Bee Soo(B22), and Pye Soo(B13) have regulatory function for the body water metabolism. The effects of acupuncture in the meridian points the Sam Cho Soo(B22) and Bee Soo(B20) were related with the changes of plasma levels of renin activity and aldosterone concentration, but the effects of acupuncture in the Pye Soo(B13) was related with the decreases of plasma levels of ANP and aldosterone.

Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>

Characterization and multicolor upconversion emission properties of BaMoO₄: Yb³⁺, Ln³⁺ (Ln = Tm, Ho, Tm/Ho) microcrystals

Ray, Schindra Kumar,Kshetri, Yuwaraj K.,Yamaguchi, Tokutaro,Kim, Tae-Ho,Lee, Soo Wohn Elsevier 2019 Journal of solid state chemistry Vol.272 No.-

<P><B>Abstract</B></P> <P>Hydrothermal process was employed to synthesize the Yb<SUP>3+</SUP>/Tm<SUP>3+</SUP>, Yb<SUP>3+</SUP>/Ho<SUP>3+</SUP> and Yb<SUP>3+</SUP>/Tm<SUP>3+</SUP>/Ho<SUP>3+</SUP> doped BaMoO<SUB>4</SUB> octahedron microcrystals (0.50–5.0 µm). The synthesized phosphors have scheelite tetragonal structure. The elemental mapping suggests the uniform distribution of elements in the samples. The oxidation state of samples were investigated by X-ray photoelectron spectroscopy (XPS) which indicates the existence of Ba<SUP>2+</SUP>, Mo<SUP>6+</SUP>, O, Yb<SUP>3+</SUP>, Tm<SUP>3+</SUP> and Ho<SUP>3+</SUP> in samples. The presence of rare earth ions was also verified by observation of specific absorption peaks in diffuse reflectance spectra (DRS). The tunable multicolor upconversion (UC) emissions were successfully obtained under 980 nm NIR excitation by precisely adjusting the concentration of rare earth ions. The as prepared sample exhibits blue, green and red emission as a result of energy transfer from the Yb<SUP>3+</SUP> to Tm<SUP>3+</SUP> and Ho<SUP>3+</SUP> ions. The power dependent UC emission spectra show the two photonic processes. The energy transfer mechanism from Yb<SUP>3+</SUP> to Tm<SUP>3+</SUP> and Ho<SUP>3+</SUP> was explained <I>via</I> an energy level analysis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Synthesis of BaMoO<SUB>4</SUB>: Yb<SUP>3+</SUP>, Ln<SUP>3+</SUP> (Ln = Tm, Ho, Tm/Ho) by hydrothermal process. </LI> <LI> Investigation of upconversion luminescence of phosphors under 980 nm excitation. </LI> <LI> Obtaining the multicolor emission by adjusting doped rare-earth ions concentration. </LI> <LI> Explanation of photonic process and energy transfer mechanism. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Multicolor upconversion emission properties of BaMoO<SUB>4</SUB>: Yb<SUP>3+</SUP>, Ln<SUP>3+</SUP> (Ln = Tm, Ho, Tm/Ho) octahedrons</P> <P>[DISPLAY OMISSION]</P>

水泳選手의 泳法別 柔軟性에 關한 硏究

李壹浩,金洙奉,金景錫 최신의학사 1992 最新醫學 Vol.35 No.3

Seed를 이용한 일방향응고 Ti-46A1-1.5Mo-0.2C 합금의 크리프 특성

李鎬年,丁仁洙,吳明勳,山口正治,韋當文 대한금속재료학회 2002 대한금속·재료학회지 Vol.40 No.1

Creep properties of directionally solidified Ti-46A1-1.5Mo-0.2C alloys with well aligned lamellar microstructure have been dramatically improved. The ingots were manufactured by seeding technique directional solidification. Directionally solidified Ti-46A1-1.5Mo-0.2C alloys showed excellent creep properties. However, the creep resistance decreased as the angle between lamellar orientation and loading axis increased. It is found that the control of the lamellar orientation is most important to improve the creep resistance of TiAI alloys. In the results of TEM analysis of creep specimen before and after creep test, it was found that no carbides were formed before creep test. But, after creep test, carbides were formed in γ lath, γ / γ interfaces, γ / α_2 interfaces and dislocations. In the case of creep test at 750℃, the quantity of carbides found in dislocations decreased as the load level increased. It was thought that superior thermal stability of Ti-46A1-1.5Mo-0.2C alloy suppressed the dynamic recrystallization and the coarsening of the lamellar microstructure, and the excellent creep resistance was maintained for long time due to this thermal stability.

응급의학과에서의 인공호흡기 처치

이삼범,도호석,도병수,이창현,심민철,권굉보 대한응급의학회 1995 대한응급의학회지 Vol.6 No.2

Study Objectives : To investigate and resolve the problems related with ventilator management in ED(emergency department). At present the ventilator is essential equipment of ED on university hospital and emergency center in Korea. Design : Retrospective consecutive case series. Setting : University teaching hospital Type of participants : All patients admitted and recieved ventilator management in ED of yeungnam university hospital from Jan. 1994 to jul. 1995. Methods and interventions : Charts of all patients were reviewed to determine the frequency, the types and causes of respiratory failure, the death rate, the mean duration of admission, the complications, and CPR(cardiopulmonary resuscitation) related with ventilator management in ED. We also identified the problems related with ventilator management by ED physicians and nurses through the answers to seven questions that suggested by us about ventilator management in ED. Measurements and main result : There were 34,751 admissions through ED during the study period. Of these 160 patients managed with ventilator in ED. The frequency of ventilator management in ED is increased at 1995(0.73%) that compared with 1994(0.32%). Non-trauma(113 cases) and hypoxic respiratory failure(83 cases) patients are more common than trauma(37 cases) and ventilatory failure Total CPR rate related with ventilator management are 25.3%. The mean duration of admission are 12.56±20.28 days, and the death rates are 45.3%. The incidence of complications occurred during ventilator management in ED are 37 cases. About seven questions suggested by us to 30 ED staffs(ED physician, nurses and paramedics), most frequent answer is the difficulty of keeping ventilator in ED because other department rent ventilator from ED and lost a part of ventilator. Conclusion : As the use of ventilator in ED is increased the emergency physician should be well trained for the indications, complications, setting mode and general problems of machine occurred during ventilator management in ED patients.