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Tetramethylpyrazine suppresses HIF-1α,TNF-α,and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats

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Acta Pharmacologica Sinica 2007年第3期28卷 327-333页

作者： Yi CHANG~(2,3) George HSIAO~4 Seu-hwa CHEN~4 Yi-cheng CHEN~4 Jiing-han LIN~4 Kuang-hung LIN~4 Duen-suey CHOU~4 Joen-rong SHEU~(4,5)2 Department of Anesthesiology,Shin Kong Wu Ho-Su Memorial Hospital,taipei 110,taiwan,china 3 school of medicine,fu-jen catholic university,taipei,110,taiwan,china 4 Graduate Institute of Medical Sciences,taipei Medical university,Tuipei 110,taiwan,china Department of Anesthesiology Shin Kong Wu Ho-Su Memorial Hospital Taipei China school of medicine Fu-Jen Catholic University Taipei China Graduate Institute of Medical Sciences Taipei Medical University Taipei China

Aim:To examine the detailed mechanisms underlying the inhibitory effect oftetramethylpyrazine(TMPZ)in inflammatory and apoptotic responses inducedby middle cerebral artery occlusion(MCAO)in ***:MCAO-inducedfocal cerebral ischemia in rats was used in this *** hypoxia-induciblefactor-1α(HIF-1α),activation of caspase-3,and TNF-αmRNA transcription inischemic regions were detected by immunoblotting and RT-PCR,***-oxidative activity was investigated using a thiobarbituric acid-reactive sub-stance(TBARS)test in rat brain homogenate ***:We showedthe statistical results of the infarct areas of solvent-and TMPZ(20 mg/kg)-treatedgroups at various distances from the frontal pole in MCAO-induced focal cerebralischemia in *** with TMPZ(20 mg/kg)markedly reduced the infarctarea in all regions,especially in the third to fifth ***-induced focalcerebral ischemia was associated with increases in HIF-lαand the activation ofcaspase-3,as well as TNF-αtranscription in ischemic *** expressionswere markedly inhibited by treatment with TMPZ(20 mg/kg).However,TMPZ(0.5-5mmol/L)did not significantly inhibit TBARS reaction in rat brain ***:The neuroprotective effect of TMPZ may be mediated at least by aportion of the inhibition of HIF-1αand TNF-αactivations,followed by the inhibi-tion of apoptosis formation(active caspase-3),resulting in a reduction in theinfarct volume in ischemia-reperfusion brain ***,TMPZ treatment mayrepresent an ideal approach to lowering the risk of or improving function in is-chemia-reperfusion brain injury-related disorders.

关键词： tetramethylpyrazine middle cerebral artery occlusion HIF-Iα caspase-3 TNF-α thiobarbituric acid-reactive substance

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Cytotoxic and apoptotic effects of prenylflavonoid artonin B in human acute lymphoblastic leukemia cells

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Acta Pharmacologica Sinica 2006年第9期27卷 1165-1174页

作者： Chun-chung LEE~2 Chun-nan LIN~3 Guey-mei JOW~(4,5)2 Department of Medical Education and Research,Shin-Kong Wu Ho-Su Memorial Hospital,taipei,taiwan china 3 school of Pharmacy,Kaohsiung Medical university,Kaohsiung,taiwan,china 4 school of medicine,fu jen catholic university,taipei Hsien 242,taiwan,china Department of Medical Education and Research Shin-Kong Wu Ho-Su Memorial Hospital Taipei China school of Pharmacy Kaohsiung Medical University Kaohsiung China school of medicine Fu Jen Catholic University Taiwan China

Aim:To investigate the anticancer effects and molecular mechanism of artonin Bon the human acute lymphoblastic leukemia CCRF-CEM cells compared with otherprenylflavonoid ***:The effects of four prenylflavonoids onthe growth of CCRF-CEM and HaCa cells were studied by 3-(4,5)-2,5-diphenyl-tetrazolium bromide(MTT)*** were detected through Hoechst33258 *** effect of artonin B on the cell cycle of CCRF-CEM cells werestudied by propidium iodide *** change in mitochondrial membranepotential was detected by rohdamine 123 *** cytochrome c release andcaspase 3 activity were checked by immunoassay kits,*** expres-sion of Bcl-2 family proteins was detected by Western ***:Our datarevealed that artonin B strongly induced human CCRF-CEM leukemia cell death ina dose-and time-dependent manner by MTT assay,but not on normal epitheliacells(HaCa cells).Artonin B-induced cell death was considered to be apoptoticby observing the typical apoptotic morphological change by Hoechst *** induction of human CCRF-CEM leukemia cancer cell death wascaused by an induction of apoptosis through mitochondrial membrane potentialchange,cytochrome c release,sub-G1 proportion increase,downregulation ofBcl-2 expression,upregulation of Bax and Bak expression and activation of caspase3 ***:These results clearly demonstrated that artonin B isable to inhibit proliferation by induction of hypoploid cells and cell ***,the anticancer effects of artonin B were related to mitochondrial path-way and caspase 3 activation in human CCRF-CEM leukemia cells.

关键词： artonin B apoptosis Bcl-2 family caspase 3 CCRF-CEM leukemia cell

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Protective effects of L-arginine on pulmonary oxidative stress and antioxidant defenses during exhaustive exercise in rats

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Acta Pharmacologica Sinica 2005年第8期26卷 992-999页

作者： Wan-teng LIN~(2,5), Suh-ching YANG~3, Kung-tung CHEN~4, Chi-chang HUANG~3, Ning-yuean LEE~(2,6) ~2 Department of Nutrition and Food Sciences, fu-jen catholic university, taipei, china ~3 school of Nutrition and Health Sciences, taipei Medical university, taipei, china ~4 Department of General Education, Ming Hsin university of Science and Technology Hsinchu, china ~5 De Lin Institute of Technology, taipei, china Department of Nutrition and Food Sciences Fu-Jen Catholic University Taipei China De Lin Institute of Technology Taipei China school of Nutrition and Health Sciences Taipei Medical University Taipei China Department of General Education Ming Hsin University of Science and Technology Hsinchu China

Aim: To assess the effects of L-arginine (L-Arg) supplementation on pulmonary oxidative stress and antioxidant defenses in rats after exhaustive exercise. Methods: Rats were randomly divided into four groups: sedentary control (SC), sedentary control with L-Arg treatment (SC+Arg), exhaustive exercise with control diet (E) and exhaustive exercise with L-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2% L-Arg diet. Rats in groups E and E+Arg underwent an exhaustive running test on a motorized treadmill. Pulmonary oxidative stress indices [xanthine oxidase (XO), myeloperoxidase (MPO), and malondialdehyde (MDA)] and antioxidant defense systems [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH)] were investigated in this study. Results: L-Arg supplementation significantly reduced exercise-induced elevations of XO and MPO activities in lung. LArg reversed the exercise-induced increase in SOD and GR activities, but increased CAT and GPX activities. L-Arg administration also significantly increased the GSH levels in plasma. Conclusion: L-Arg supplementation can prevent elevations of XO and MPO activities in the lung and favorably influence pulmonary antioxidant defense systems after exhaustive exercise.

关键词： L-arginine oxidative stress xanthine oxidase myeloperoxidase exhaustive exercise lung

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Is inconsistency of α-fetoprotein level a good prognosticator for hepatocellular carcinoma recurrence?

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World Journal of Gastroenterology 2010年第24期16卷 3049-3055页

作者： Chung-Bao Hsieh, Teng-Wei Chen, Division of General Sur-gery, Tri-Service General Hospital, taipei 114, taiwan, china Chung-Bao Hsieh, Kuo-Piao Chung, Graduate Institute of Health Care Organization Administration, National taiwan university, taipei 100, taiwan, china Chi-Ming Chu, Section of Biostatistics and Informatics, De-partment of Epidemiology, school of Public Health, National Defense Medical Center, taipei 114, taiwan, chinaHeng-Cheng Chu, Department of Internal medicine, Tri-Service General Hospital, taipei 114, taiwan, chinaCheng-Ping Yu, Department of Pathology, Tri-Service General Hospital, taipei 114, taiwan, china Division of General Surgery Tri-Service General Hospital Taipei 114 Taiwan China.

AIM: To identify the clinical outcomes of hepato-cellular carcinoma (HCC) patients with inconsistent α-fetoprotein (AFP) levels which were initially high and then low at ***: We retrospectively included 178 patients who underwent liver resection with high preoperative AFP levels (≥ 200 ng/dL). Sixty-nine HCC patients had recurrence during follow-up and were grouped by their AFP levels at recurrence: group Ⅰ, AFP ≤ 20 ng/dL (n = 16); group Ⅱ, AFP 20-200 ng/dL (n = 24); and group Ⅲ, AFP ≥ 200 ng/dL (n = 29). Their preoperative clinical characteristics, accumulated recurrence rate, and recurrence-to-death survival rate were compared. Three patients, one in each group, underwentliver resection twice for primary and recurrent HCC. AFP immunohistochemistry of primary and recurrent HCC specimens were ***: In this study, 23% of patients demon-strated normal AFP levels at HCC recurrence. The AFP levels in these patients were initially high. There were no significant differences in clinical characteristics between the three groups except for the mean recur-rence interval (21.8 ± 14.6, 12.3 ± 7.7, 8.3 ± 6.6 mo, respectively, P 36.1 ± 22.4, 21.9 ± 22.0 mo, respectively, P = 0.013). Tumor size > 5 cm, total bilirubin > 1.2 mg/dL, vessel invasion, Child classification B, group Ⅲ, and recurrence interval < 12 mo, were risk factors for survival rate. Cox regression analysis was performed and vessel invasion, group Ⅲ, and recurrence interval were independent risk factors. The recurrence inter-val was significant longer in group Ⅰ (P < 0.001). The recurrence-to-death survival rate was significantly bet-ter in group Ⅱ (P = 0.016). AFP staining was strong in the primary HCC specimens and was reduced at recur-rence in group Ⅰ ***: Patients in group Ⅰ with inconsistent AFP levels had a longer recurrence interval and worse recurrence-to-death survival rate than those in group Ⅱ. This clinical presentatio

关键词： Hepatocellular carcinoma Inconsistent α-fetoprotein Outcome Recurrence

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Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors

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Acta Pharmacologica Sinica 2005年第6期26卷 685-690页

作者： Hua HU~(2,3), Gao CHEN~2, Jian-min ZHANG~2, Wei-ping ZHANG~3, Lei ZHANG~3, Qiu-fu GE~3, Hong-tian YAO~4, WeiDING~4, Zhong CHEN~3, Er-qing WEI~(3,5) ~2 Department of Neurosurgery, the Second Affiliated Hospital, school of medicine, Zhejiang university, Hangzhou 310009 ~3 Department of Pharmacology school of medicine, Zhejiang university, Hangzhou 310031 ~4 Department of Pathology, the First Affiliated Hospital, school of medicine, Zhejiang university, Hangzhou 310003, china Department of Neurosurgery the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou China Department of Pharmacology School of Medicine Zhejiang University Hangzhou China Department of Pathology the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou China

Aim: To determine the distribution of cysteinyl leukotriene receptor 2 （CysLT2）, one of the cysteinyl leukotriene receptors, in human brains with traumatic injury and tumors. Methods: Brain specimens were obtained from patients who underwent brain surgery. CysLT2in brain tissues was examined using immunohis-tochemical analysis. Results: CysLT2was expressed in the smooth muscle cells （not in the endothelial cells） of arteries and veins. CysLT2was also expressed in the granulocytes in both vessels and in the brain parenchyma. In addition, CysLT2was detected in neuron- and glial-appearing cells in either the late stages of traumatic injury or in the area surrounding the tumors. Microvessels regenerated 8 d after trauma and CysLT2expression was recorded in their endothelial cells. Conclusion: CysLT2is distributed in vascular smooth muscle cells and granulocytes, and brain trauma and tumor can induce its expression in vascular endothelial cells and in a number of other cells.

关键词： cysteinyl leukotriene receptor 2 brain injuries brain neoplasms vascular smooth muscle cell

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3D printed grafts with gradient structures for organized vascular regeneration

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International Journal of Extreme Manufacturing 2024年第3期6卷 505-520页

作者： Yuewei Chen Zhongfei Zou Tao fu Zhuang Li Zhaojie Zhang Meng Zhu Qing Gao Shaofei Wu Guosheng fu Yong He Jiayin fu State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China school of Mechanical Engineering Guizhou UniversityGuiyang 550025People’s Republic of China Key Laboratory of Cardiovascular Intervention and Regenerative medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalZhejiang UniversityHangzhou 310016People’s Republic of China school of Mechanical Engineering Guizhou Institute of TechnologyGuiyang 550003People’s Republic of China Department of Oral and Maxillofacial Surgery The Second Affiliated Hospital of Zhejiang University School of MedicineSchool of Stomatologyand Key Laboratory of Oral Biomedical Research of Zhejiang ProvinceHangzhouZhejiang 310006People’s Republic of China

Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great ***,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis and stenosi... 详细信息

Synthetic vascular grafts suitable for small-diameter arteries(3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural *** by the collagen alignment of SML,the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment,which could facilitate SML reconstruction for compliance restoration and spontaneous *** outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical *** month after implantation,the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts,with a compliance(8.9%) approaching that of natural arteries(11.36%) and significantly higher than that of electrospun ones(1.9%).The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature *** study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.

关键词： small-diameter vascular graft smooth muscle layer 3D printing endothelialization

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Both gain-and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia

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Journal of Genetics and Genomics 2024年第8期51卷 801-810页

作者： Wan-Bing Sun Jing-Xin fu Yu-Lan Chen Hong-fu Li Zhi-Ying Wu Dian-fu Chen Department of Medical Genetics and Center for Rare Diseases and Department of Neurologyand Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation in Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Nanhu Brain-computer Interface Institute HangzhouZhejiang 314050China MOE Frontier Science Center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310012China

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channelα*** variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia(PKD),but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD *** the whole exome sequencing followed by Sanger sequencing,we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese *** proband of one family(c.496G>A,p.A166T)manifests as episodic ataxia type 1,and the other two(c.877G>A,p.V293I and c.1112C>A,p.T371A)manifest as *** pathogenicity of these variants is confirmed by functional studies,suggesting that p.A166T and p.T371A cause a loss-of-function of the channel,while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic *** reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein,we find that these variants tend to cluster around the pore domain,which is similar to ***,our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype–phenotype correlations of KCNA1 channelopathy.

关键词： Paroxysmal kinesigenic dyskinesia KCNA1 Loss-of-function Gain-of-function Channelopathy Episodicataxiatype1

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Mathematics of multi-agent learning systems at the interface of game theory and artificial intelligence

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Science china(Information Sciences) 2024年第6期67卷 445-447页

作者： Long WANG Feng fu Xingru CHEN Center for Systems and Control College of EngineeringPeking University Center for Multi-Agent Research Institute for Artificial IntelligencePeking University Department of Mathematics Dartmouth College Department of Biomedical Data Science Geisel School of Medicine at Dartmouth school of Science Beijing University of Posts and Telecommunications

Evolutionary game theory (EGT) and artificial intelligence(AI) are two fields that,at first glance,might seem distinct,but they have notable connections and *** former focuses on the evolution of behaviors (or strategies)in a population,where individuals interact with others and update their strategies based on imitation (or social learning).

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ONO-1078 reduces NMDA-induced brain injury and vascular cell adhesion molecule-1 expression in rats

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Acta Pharmacologica Sinica 2005年第4期26卷 435-440页

作者： Li-hui ZHANG~(2,3) Er-qing WEI~(2,4) 2 Department of Pharmacology,school of medicine,Zhejiang university,Hangzhou 310031 3 Medical school,Hangzhou Normal university,Hangzhou 310018,china Department of Pharmacology School of Medicine Zhejiang University Hangzhou China Medical school Hangzhou Normal University Hangzhou China

Aim:To determine whether ONO-1078 （pranlukast）,a potent cysteinyl leukotrienereceptor 1 （CysLTI） antagonist,has an effect on N-methyl-D-aspartate （NMDA）-induced brain injury and vascular cell adhesion molecule-1 （VCAM-1） expres-sion in ***:Brain injury was induced by direct microinjection of NMDA（0.3 μmol in 1 μL of sterile 0.1 mol/L PBS,pH 7.4） into the cerebral *** volume （area）,brain edema and neuron density were assessed by an imageanalyzer and the expression of VCAM-1 in the cortex was detected by Westernblot 24 h after NMDA ***-1078 （0.03,0.1,or 0.3 mg/kg） andedaravone （MCI-186,10 mg/kg）,a neuroprotective agent,were ip injected 30rain before and after NMDA ***:NMDA microinjection producedwell-defined focal lesions （Figure 1） dose- and ***-1078（0.1,0.3 mg/kg） and edaravone （10 mg/kg） decreased the total lesion volume,lesion area and brain edema induced by ***,ONO-1078 （0.1,0.3mg/kg） significantly inhibited the enhanced expression of VCAM-1 in the injuredcortices,but edaravone did not have this ***:CysLT1receptorantagonist ONO-1078 at tenufftes NMDA-induced brain damage in rats,and thismight relate to the attenuation of NMDA receptor-dependent neurotoxicity andthe inhibition of the upregulation of VCAM-1 expression.

关键词： leukotriene antagonists pranlukast N-methylaspartate vascular cell adhesion molecule-1 neurotoxicity brain injuries

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Problem-based learning in pharmacology:a survey of department heads in taiwan, china

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Acta Pharmacologica Sinica 2004年第9期 137-139页

作者： Ying-tung LAUDepartment of Physiology and Pharmacology school of medicine, Chang Cung university, Taoyuan, taiwan, china

Problem-based learning (PEL) requires active student participation and the use of clinical cases as a trigger to learn within a given area. It has gained much attention as a pedagogic alternative in the course of reform in medical education due to information overload. From discipline-based consideration, it is interesting to understand the views of department heads of pharmacology about implementing PBL for their medical students. According to a

关键词： problem-based learning pharmacology medical education

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