V. vulnificus의 cyolysin에 의해 형성된 Pored의 이온 투과성에 관한 연구

마천택 ( Tian Ze Ma ),홍병철 ( Bing Zhe Hong ),고경희 ( Hee Ko Kyeung ) 전북대학교 의과학연구소 2004 全北醫大論文集 Vol.28 No.1

V. vulnificus가 분비하는 cytolysin의 pore 형성 효과를 전기생리학적으로 확인하고 그 pore의 이온선택성을 밝히고자, V. vulnificus cytolysin의 표적세포로 예산되는 폐내피세포인 CPAE 세포에서 여러 bath용액에서의 cytolysin pore의 이온투과성을 비교 관찰하여 다음과 같은 결과를 얻었다. 1. Cytolysin 1 HU/ml을 세포내외에 투여시 2-7분의 lag time 후 sensitivity 차이없이 115.6 ± 5.1 pS의 단일 전도도를 갖는 pore를 시간 의존적으로 형성하였으며, 이런 pore의 이온투과성은 세척 후에도 지속적으로 유지되었다. 2. Bath용액의 140 mM KCI을 같은 농도의 NaC1 및 CsC1로 치환하여도 cytolysin pore 의 이온투과성에는 유의한 변동이 없었다. 3. Bath용액의 140 mM KCI을 같은 농도의 CaC1(2) 및 BaCl2로 치환하면 cytolysin pore의 이온투과성이 각각 1.8배와 2.3배로 현저하게 증가하였다. 4. Bath용액의 C1 농도를 동일하게 하고자, 각각 140 mM KCI과 70 mM MgC1(2)로 치환시 cytolysin pore의 이온투과성에는 유의한 차이가 없었다. 5. Bath용액의 KCI농도를 140 mM에서 10mM과 1 Mm로 감소시 cytolysin pore의 역전전압이 0 mV에서 각각 -31.1 ± 1.5mV와 -42.3 ± 1.8 mV로, C1 이온의 역전전압에 근접하게 이동하였다. 이상의 실험결과를 종합하변, V. vulnificus cytolysin은 세포막내외의 차이없이 시간의존 적인 pore를 형성하는데, 이 pore의 투과성은 막전위에 비의존적이며 주로 C1 이온에 선택성이 높음을 시사한다. Cytolysin produced by V. vulnificus has been incriminated as one of the important virulence determinants in V. vulnificus infection. Ion selectivity of cytolysin-induced pres has been examined in CPAE cells, a cell line of pulmonary endothelial cells, using inside-out patch clamp techniques. In symmetrical KCI concentration (140 mM). intracellular and extracellular cytolysin formed the ion-permeable pores with single channel conductance of 115.6±5.1 pS (n=6) in a time-dependent manner and a voltage-independent manner. The pore currents were consistently maintained after washout of cytolysin. Replacement of intracellular 140 mM KCI with 140 mM NaCl, 140 mM CsCl and 70 mM MgCl2 did not affect the pore currents, but replacement of it with equimolar CaCl2 and BaCl2 increased the pore current by 1.8 and 2.4 times of control current (140 mM KCL), respectively. When the intracellular KCI concentration was lowered from 140 to 10 and 1 mM, zero-current membrane potentials shifted from 0 mV to -31.1 ± 1.5 and -42.3 ± 1.8 mV, respectively. These results indicate that cytolysin produced by V. vulnificus formed the CI(-) -selective pores in CPAE cells.

The effect of HCP on the formation of twin boundaries and dislocations in Ni–Co alloys

Ma Rui-bo,Zhou Li-li,Liang Yong-chao,Chen Qian,Tian Ze-an,Liu Rang-su,Mo Yun-fei,Gao Ting-hong,Xie Quan 한국물리학회 2021 Current Applied Physics Vol.29 No.-

In this study, molecular dynamics (MD) was used to simulate the rapid solidification process of Ni47Co53 and Ni48Co52 alloys at a cooling rate of 1012 K/s. The effects of HCP on the formation of twin boundaries and dislocations in two Ni–Co alloys are studied. It is found that the difference of HCP clusters is the main effect that producing discrepancies on microstructure of two alloys. The number of HCP clusters accounted for 9.23% in Ni47Co53 alloy. They are regularly arranged to form the number of single-layer twin boundaries, and each twin boundary ends in a dislocation. The FCC and HCP structures coexist in the same atomic layers, which is easy to create dislocations. The relatively standard FCC crystal and only 0.32% HCP clusters are formed in Ni48Co52 alloy at 300 K. That small amount of HCP clusters are dispersed on the surface, and cause the formation of dislocation in the border with FCC clusters.

Synthesis of Psoralen Derivatives and Their Blocking Effect of hKv1.5 Channel

은재순,김광식,김한나,박선아,Tian-Ze Ma,이경아,김대근,김형교,김인수,정영훈,지옥표,유동진,곽용근 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.2

Previously, we found that a furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7- one), blocked a human Kv1.5 potassium channel (hKv1.5) and has a potential antiarrhythmic effect. In the present study, to develop more potent hKv1.5 blockers or antiarrhythmic drugs, we synthesized ten psoralen derivatives and examined their blocking effects on hKv1.5 stably expressed in Ltk- cells. Among the newly synthesized psoralen derivatives, three derivatives (Compounds 5, 9 and 10) showed the open channel-blocking effect. Compound 9 among them was the most potent in blocking hKv1.5. We found that compound 9, one of the psoralen derivatives, inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC50 value of 27.4 ± 5.1 nM at +60 mV. Compound 9 accelerated the inactivation kinetics of the hKv1.5 channel, slowed the deactivation kinetics of hKv1.5 current resulting in a tail crossover phenomenon. Compound 9 inhibited hKv1.5 current in a use-dependent manner. These results indicate that compound 9, one of psoralen derivatives, acts on hKv1.5 channel as an open channel blocker and is much more potent than psoralen in blocking hKv1.5 channel. If further studies were done, compound 9 might be an ideal antiarrhythmic drug for atrial fibrillation.

Artemongolins A–K, undescribed germacrane-guaiane sesquiterpenoid dimers from Artemisia mongolica and their antihepatoma activities

Chong Shang,Yun-Bao Ma,Yuan Wang,Xiao-Feng He,Tian-Ze Li,Ji-Jun Chen 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.10

Artemongolins A–K (1–11), which are undescribed sesquiterpenoid dimers, were obtained from Artemisia mongolica and characterized through comprehensive spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculations. The absolute configurations of compounds 1, 4, and 7 were undoubtedly determined by a single-crystal X-ray crystallography. Artemongolins A–K (1–11) featured a rare 5/7/5/5/5/10 hexacyclic system composed of a germacrene and a guaianolide by a fused 2-oxaspiro[4,4]nonane-1-one ring system. Antihepatoma evaluation against three human hepatoma cell lines demonstrated that the most active compounds 5 and 6 displayed inhibitory activity with IC50 values of 88.6 and 57.0 (HepG2), 59.1 and 26.4 (Huh7), and 67.5 and 32.5 (SK-Hep-1) µM, respectively.

Torilin from Torilis japonica (Houtt.) DC. Blocks hKv1.5 Channel Current

Yong Geun Kwak,김대근,Tian-Ze Ma,박선아,Hoon Park,정영훈,유동진,은재순 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.10

Torilin was purified from Torilis japonica (Houtt.) DC., and its effects on a rapidly activating delayed rectifier K+ channel (hKv1.5), cloned from human heart and stably expressed in Ltk- cells, as well as the corresponding K+ current (the ultrarapid delayed rectifier, IKUR) were assessed in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, torilin was found to inhibit the hKv1.5 current in time and voltage-dependent manners, with an IC50 value of 2.51±0.34 μM at +60 mV. Torilin accelerated the inactivation kinetics of the hKv1.5 channel, and slowed the deactivation kinetics of the hKv1.5 current, resulting in a tail crossover phenomenon. Additionally, torilin inhibited the hKv1.5 current in a usedependent manner. These results strongly suggest that torilin is a type of open-channel blocker of the hKv1.5 channel.

Comparative Analysis of Serum Proteomes of Moyamoya Disease and Normal Controls

Koh, Eun-Jeong,Kim, Han-Na,Ma, Tian-Ze,Choi, Ha-Young,Kwak, Yong-Geun The Korean Neurosurgical Society 2010 Journal of Korean neurosurgical society Vol.48 No.1

Objective : The etiology and pathogenesis of moyamoya disease remain unclear. Furthermore, the definitive diagnostic protein-biomarkers for moyamoya disease are still unknown. The present study analyzed serum proteomes from normal controls and moyamoya patients to identify novel serological biomarkers for diagnosing moyamoya disease. Methods : We compared the two-dimensional electrophoresis patterns of sera from moyamoya disease patients and normal controls and identified the differentially-expressed spots by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry and electrospray ionization quadruple time-of-flight mass spectrometry. Results : We found and analyzed 22 differently-expressed proteomes. Two proteins were up-regulated. Twenty proteins were down-regulated. Complement C1 inhibitor protein and apolipoprotein C-III showed predominantly changed expressions (complement C1 inhibitor protein averaged a 7.23-fold expression in moyamoya patients as compared to controls, while apolipoprotein C-III averaged a 0.066-fold expression). Conclusion : Although our study had a small sample size, our proteomic data provide serologic clue proteins for understanding moyamoya disease.

Torilin from Torilis japonica (Houtt.) DC. Blocks hKv1.5 Channel Current

Kwak, Yong-Geun,Kim, Dae-Keun,Ma, Tian-Ze,Park, Sun-Ah,Park, Hoon,Jung, Young-Hoon,Yoo, Dong-Jin,Eun, Jae-Soon The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.10

Torilin was purified from Torilis japonica (Houtt.) DC., and its effects on a rapidly activating delayed rectifier $K^+$ channel (hKv1.5), cloned from human heart and stably expressed in Ltk cells, as well as the corresponding $K^+$ current (the ultrarapid delayed rectifier, $I_{KUR}$) were assessed in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, torilin was found to inhibit the hKv1.5 current in time and voltage-dependent manners, with an $IC_50$ value of $2.51{\pm}0.34\;{\mu}M$ at +60 mV. Torilin accelerated the inactivation kinetics of the hKv1.5 channel, and slowed the deactivation kinetics of the hKv1.5 current, resulting in a tail crossover phenomenon. Additionally, torilin inhibited the hKv1.5 current in a use dependent manner. These results strongly suggest that torilin is a type of open-channel blocker of the hKv1.5 channel.

Basic Fibroblast Growth Factor Increases Intracellular Magnesium Concentration through the Specific Signaling Pathways

Bing-Zhe Hong,박선아,Han-Na Kim,Tian-Ze Ma,Han-Gyu Kim,강형섭,김환규,곽용근 한국분자세포생물학회 2009 Molecules and cells Vol.28 No.1

Basic fibroblast growth factor (bFGF) plays an important role in angiogenesis. However, the underlying mechanisms are not clear. Mg2+ is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of bFGF on the intracellular Mg2+ concentration ([Mg2+]i) in human umbilical vein endothelial cells (HUVECs). bFGF increased [Mg2+]i in a dose-dependent manner, independent of extracellular Mg2+. This bFGF-induced [Mg2+]i increase was blocked by tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and a phospholipase Cγ (PLCγ) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) did not affect the bFGF-induced [Mg2+]i increase. These results suggest that bFGF increases the [Mg2+]i from the intracellular Mg2+ stores through the tyrosine kinase/PI3K/PLCγ- dependent signaling pathways.

Efficacy of Prophylactic Entecavir for Hepatitis B Virus-Related Hepatocellular Carcinoma Receiving Transcatheter Arterial Chemoembolization

Li, Xing,Zhong, Xiang,Chen, Zhan-Hong,Wang, Tian-Tian,Ma, Xiao-Kun,Xing, Yan-Fang,Wu, Dong-Hao,Dong, Min,Chen, Jie,Ruan, Dan-Yun,Lin, Ze-Xiao,Wen, Jing-Yun,Wei, Li,Wu, Xiang-Yuan,Lin, Qu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18

Background and Aims: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.

Staged Improvement in Awareness of Disease for Elderly Cancer Patients in Southern China

Li, Xing,Dong, Min,Wen, Jing-Yun,Wei, Li,Ma, Xiao-Kun,Xing, Yan-Fang,Deng, Yun,Chen, Zhan-Hong,Chen, Jie,Ruan, Dan-Yun,Lin, Ze-Xiao,Wang, Tian-Tian,Wu, Dong-Hao,Liu, Xu,Hu, Hai-Tao,Lin, Jia-Yu,Li, Zhu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. Materials and Methods: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. Results: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision-making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. Conclusions: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.