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Optical substrates for drug-metabolizing enzymes: Recent advances and future perspectives

Acta Pharmaceutica Sinica B 2022年第3期12卷 1068-1099页

作者： Qiang Jin Jing Jing Wu Yue Wu Hongxin Li Moshe Finel Dandan Wang Guangbo Ge Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China Department of Clinical Pharmacology College of PharmacyDalian Medical UniversityDalian 116044China Division of Pharmaceutical Chemistry and Technology Faculty of PharmacyUniversity of HelsinkiHelsinki 00014Finland

Drug-metabolizing enzymes(DMEs),a diverse group of enzymes responsible for the metabolic elimination of drugs and other xenobiotics,have been recognized as the critical determinants to drug safety and *** and understanding the key roles of individual DMEs in drug metabolism and toxicity,as well as characterizing the interactions of central DMEs with xenobiotics require reliable,practical and highly specific tools for sensing the activities of these enzymes in biological *** the last few decades,the scientists have developed a variety of optical substrates for sensing human DMEs,parts of them have been successfully used for studying target enzyme(s)in tissue preparations and living ***,molecular design principals and recent advances in the development and applications of optical substrates for human DMEs have been reviewed ***,the challenges and future perspectives in this field are also *** presented information offers a group of practical approaches and imaging tools for sensing DMEs activities in complex biological systems,which strongly facilitates high-throughput screening the modulators of target DMEs and studies on drug/herb-drug interactions,as well as promotes the fundamental researches for exploring the relevance of DMEs to human diseases and drug treatment outcomes.

关键词： Optical substrates Drug-metabolizing enzymes(DMEs) Fluorescence-based assay High-throughput screening

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Curative effect of heat-sensitive moxibustion on chronic persistent asthma: a multicenter randomized controlled trial

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Journal of traditional Chinese medicine 2013年第5期33卷 584-591页

作者： Rixin Chen Mingren Chen Jun Xiong Zhenhai Chi B0 Zhang Ning Tian Zhenhua Xu Tangfa Zhang Wanyao Li Wei Zhang Xiaofeng Rong Zhen Wang Gang Sun Baohe Ge Guoxiong Yu Nanchang Song Department of Acupuncture and Rehabilitation Hospital Affiliated to Jiangxi University of Traditional Chi-nese Medicine Department of Rehabilitation Guangdong Hos-pital of Combination of Traditional Chinese Medicine with Western Medicine Department of Pneumology Guangdong Hos-pital of Traditional Chinese Medicine Department of Acupuncture First Hospital of Wuhan institute of Acupuncture and Massage Guang-zhou University of Traditional Chinese Medicine Department of Pneumology First Hospital Affili-ated to Nanchang University Department of Rehabilitation First Hospi-tal Affiliated to Chongqing Medical University Department of Acupuncture First Hospital Af-filiated to Zhejiang University of Traditional Chinese Medi-cine Department of Acupuncture Suzhou Hospital of TCM Department of Acupuncture Hospital Affiliated to Shandong University of Traditional Chinese Medicine Department of Acupuncture Guangdong Dis-abled Soldier Hospital Department of Acupuncture Nanchang Hospital of combination of Traditional Chinese Medicine with Western Medicine

OBJECTIVE:To compare the curative effects of heat-sensitive moxibustion with conventional drugs on chronic persistent asthma and seek a valuable therapy to replacewestern ***:The participants in this multi-center,randomized,and controlled study were randomly divided into two groups:group A(n=144),treated with heat-sensitive moxibustion(50 sessions)and group B(n=144),treated with Seretide(salmeterol50μg/fluticasone 250μg,twice a day).The scores of asthma control test(ACT),forced expiratory volume in 1 second(FEV1),peak expiratory flow(PEF),and attack frequency were measured after 15,30,60,and 90 days of *** followed up3 and 6 months after ***:There was a significant difference(P=0.0002)in the ACT score and lung function between the two groups after 3 months of treatment and(P=0.000 03)during the follow-up *** addition,heat-sensitive moxibustion reduced attack frequency in the period from inclusion to the6-month follow-up ***:This study shows that heat-sensitive moxibustion may have a comparable curative effect toSeretide(salmeterol/fluticasone)on asthma.

关键词： Moxibustion Asthma Randomized controlled trial Heat sensitive Seretide

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Reduning injection for fever, rash, and ulcers in children with mild hand, foot, and mouth disease: a randomized controlled clinical study

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Journal of traditional Chinese medicine 2013年第6期33卷 733-742页

作者： Guoliang Zhang Jie Zhao Liyun He Shiyan Yan Ziqiang Zhuo Haojie Zheng Yongping Mu Shuangjie Li Xi Zhang Jihan Huang Xiuhui Li Jianping Liu Hehe Wan Chaoyu Wei Wei Xiao Department of Infectious Disease the First Affiliated Hospital of Anhui University of Chinese Medicine Graduate Faculty Anhui University of Chinese Medicine Chinese medical Clinical Basic research institute China Academy of Chinese Medical Sciences Department of Infectious Disease Quanzhou Children's Hospital Department of Combine traditional Chinese and western medicine Department of Combine traditional Chinese and western medicine Shanghai Public Health Centre Department of Infectious Disease Hunan Provincial Children's Hospital Department of Infectious Disease Kaifeng Children's Hospital Drug Clinical research Center Shanghai University of Chinese Medicine Department of Combine traditional Chinese and western medicine Youan Hospital Evidence Based medical Center Beijing University of Chinese Medicine Department of research and Development Jiangsu Kanion Pharmaceutical Llc.

OBJECTIVE： To assess the efficacy and safety of Re- duning injection for fever, rash, and ulcers in chil- dren with mild hand, foot, and mouth disease （HFMD）. METHODS： A stratified-block randomized, dou- ble-blind, parallel-controlled, and multicenter clini- cal trial was conducted with 360 patients in five hospitals across China： Quanzhou Children＇s Hospi- tal, Shijiazhuang No. 5 Hospital, Shanghai Public Health Centre, Hunan Provincial Children＇s Hospi- tal, and Kaifeng Children＇s Hospital. Patients were randomized into three groups with 120 in each. Group A was treated with western medicine, group B with Reduning injection, a Chinese herbal medi- cine, and group C with both Reduning injection and western medicine. Results were compared for treatment efficacy and safety on HFMD. The clinical outcomes were observed as follows： fever and on- set time of antifebrile effect （time to bring the body temperature down 〉0.5~C after medication）; cumu- lative time for fever recovery （body temperature re- covering to normal and lasting more than 24 h without medication）; cumulative time for rash dis- appearance （without new rashes or ulcers appear- ing and the original ones fading away）; and cumula- tive time for mouth ulcer disappearance. RESULTS： For the onset time of the antifebrile ef- fect, there was no statistical difference between groups A and B （P〉O.05） and groups B and C （P〉 0.05）. However, there was a statistical difference be- tween groups A and C （P〈0.05）, and the effect ingroup C was the best. For the cumulative time for rash disappearance, there was no statistical differ- ence between groups A and B （P〉0.05）. There were statistical differences between groups A and C, and groups B and C （P〈0.05）, and the effect in group C was the best. For the cumulative time for mouth ul- cers disappearance, there were no statistical differ- ences among the three groups （P〉0.05）. CONCLUSION： Reduning injection with western medicine for symptomatic treatment is most effec- tive

关键词： Hand, foot and mouth disease Symp-tomatic therapy Randomized controlled trial Treat-ment outcome Reduning injection

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Integration of traditional Chinese medicine and western medicine in the era of precision medicine

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Journal of Integrative medicine 2017年第1期15卷 1-7页

作者： Wen-jian Wang Teng Zhang institute of Integrative medicine Huashan Hospital Fudan University Clinical research institute of Chinese Integrative medicine Shanghai Academy of Traditional Chinese Medicine Yueyang Hospital of Chinese Integrative medicine Shanghai University of Traditional Chinese Medicine

Precision medicine has received growing recognition from clinicians, health systems, and the pharmaceutica industry, as well as patients and policymakers, which will leave a major impact on the practice of medicine. Interestingly, traditional Chinese medicine （TCM） provides personalized medical treatment based on the theory of TCM characterized by holistic concept and pattem differentiation. This, to some extent, is similar to the personalized medical treatment of precision medicine. In China, TCM as well as western medicine （WM） plays an important role in healthcare. In this article, the authors summarized the influence of precision medicine on current medical directions, the advantages of TCM in disease treatment, further development of precision medicine and the strategies for integration of TCM and WM under this new treatment approach. In addition, the authors discuss the perspective of precise medical diagnosis and treatment, precise prevention, and the complementary advantages of the integration of TCM and WM. Finally, the authors give their perspectives on the challenges and opportunities presented by precision medicine, in the context of further research toward the integration of TCM and WM.

关键词： precision medicine medicine, Chinese traditional western medicine integrative medicine

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Production of chitosan scaffolds by lyophilization or electrospinning: which is better for peripheral nerve regeneration?

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Neural Regeneration research 2021年第6期16卷 1093-1098页

作者： Yu-Xuan Wu Hao Ma Jian-Lan Wang Wei Qu Department of Hand Microsurgery First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of traditional Chinese medicine First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina

Both lyophilization and electrospinning are commonly used to make chitosan ***,it remains unknown which method is better for cell *** this study,we established the following groups:(1)lyophilization group-chitosan scaffolds were prepared by lyophilization method and seeded with Schwann cells from Sprague-Dawley rats aged 3-5 days;(2)electrospinning group-chitosan scaffolds were prepared by electrospinning method and seeded with Schwann cells;(3)control group-Schwann cells were cultured on culture *** growth of Schwann cells was evaluated by immunofluorescence and scanning electron *** blot assay was performed to explore the mechanism of Schwann cell *** materials were non-toxic and suitable for the growth of Schwann *** pores produced by electrospinning were much smaller than those produced by *** proliferation rate and adhesion rate of Schwann cells in the electrospinning group were higher than those in the lyophilization *** cells cultured on electrospinning scaffolds formed a Bungner band-like structure,and a much greater amount of brain-derived neurotrophic factor was secreted,which can promote the growth of *** findings show that the chitosan scaffold prepared by the electrospinning method has a nanofiber structure that provides an extracellular matrix that is more favorable for cell-cell *** electrospinning method is more suitable for nerve regeneration than the lyophilization *** research was approved by the medical Ethical Committee of dalian medical university(approval ***1-2016-045)on March 3,2016.

关键词： cells factor growth in vitro model peripheral nerve plasticity protein rat regeneration

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Fuzheng Huayu recipe, a traditional Chinese compound herbal medicine, attenuates renal interstitial fibrosis via targeting the miR-21/PTEN/AKT axis

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Journal of Integrative medicine 2020年第6期18卷 505-513页

作者： Qing-lan Wang Yan-yan Tao Hong-dong Xie Cheng-hai Liu Ping Liu Teaching&research Department of Clinical and Classic medicine College of Basic Medical Science.Shanghai University of Traditional Chinese MedicineShanghai 201203.China E-institute of Shanghai Municipal Education Committee Shanghai University of Traditional Chinese MedicineShanghai 210203China institute of Liver Diseases Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 210203China

Objective: MicroRNAs(miRNAs) may be viable targets for treating renal interstitial fibrosis(RIF). Fuzheng Huayu recipe(FZHY), a traditional Chinese compound herbal medicine, is often used in China to treat fibrosis. This study sought to assess the mechanisms through which FZHY influences miRNAs to treat ***: RIF was induced in rats by mercury chloride and treated with FZHY. Hydroxyproline content,Masson’s staining and type I collagen expression were used to evaluate renal collagen *** miRNA profiles were evaluated using a miRNA microarray. Those miRNAs that were differentially expressed following FZHY treatment were identified and subjected to bioinformatic analyses. The miR-21 target gene phosphatase and tensin homolog(PTEN) expression and AKT phosphorylation in kidney tissues were assessed via western blotting. In addition, HK-2 human proximal tubule epithelial cells were treated using angiotensin II(Ang-II) to induce epithelial-to-mesenchymal transition(EMT), followed by FZHY exposure. miR-21 and PTEN expressions were evaluated via quantitative reverse transcriptionpolymerase chain reaction(qRT-PCR), while E-cadherin and a-smooth muscle actin(a-SMA) expressions were assessed by immunofluorescent staining and qRT-PCR. western blotting was used to assess PTEN and AKT ***: FZHY significantly decreased kidney collagen deposition, hydroxyproline content and type I collagen level. The miRNA microarray identified 20 miRNAs that were differentially expressed in response to FZHY treatment. Subsequent bioinformatic analyses found that miR-21 was the key fibrosis-related miRNA regulated by FZHY. FZHY also decreased PTEN expression and AKT phosphorylation in fibrotic kidneys. Results from in vitro tests also suggested that FZHY promoted E-cadherin upregulation and inhibited a-SMA expression in Ang-II-treated HK-2 cells, effectively reversing Ang-II-mediated EMT. We also determined that FZHY reduced miR-21 expression, increased PTEN ex

关键词： Fuzheng Huayu recipe Chinese herbal medicine Renal interstitial fibrosis miR-21 PTEN AKT microRNA

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Aphasia rehabilitation based on mirror neuron theory: a randomized-block-design study of neuropsychology and functional magnetic resonance imaging

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Neural Regeneration research 2019年第6期14卷 1004-1012页

作者： Wen-Li Chen Qian Ye Si-Cong Zhang Yang Xia Xi Yang Ti-Fei Yuan Chun-Lei Shan Jian-An Li Department of Rehabilitation medicine The First Affiliated Hospital of Nanjing Medical University Department of Rehabilitation medicine Zhangjiagang Hospital Affiliated to Nanjing University of Chinese Medicine School of Rehabilitation Sciences Nanjing Normal University of Special Education Yueyang Hospital of integrated Chinese and western medicine Shanghai University of Traditional Chinese Medicine Department of Rehabilitation medicine Zhongda HospitalSoutheast University Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of Medicine School of Rehabilitation Science Shanghai University of Traditional Chinese Medicine institute of Rehabilitation medicine Shanghai Academy of Traditional Chinese Medicine

When watching someone performs an action, mirror neurons are activated in a way that is very similar to the activation that occurs when actually performing that action. Previous single-sample case studies indicate that hand-action observation training may lead to activation and remodeling of mirror neuron systems, which include important language centers, and may improve language function in aphasia patients. In this randomized-block-design experiment, we recruited 24 aphasia patients from, Zhongda Hospital, Southeast university, China. The patients were divided into three groups where they underwent hand-action observation and repetition, dynamic-object observation and repetition, or conventional speech therapy. Training took place 5 days per week, 35 minutes per day, for 2 weeks. We assessed language function via picture naming tests for objects and actions and the western Aphasia Battery. Among the participants, one patient, his wife and four healthy student volunteers underwent functional magnetic resonance imaging to analyze changes in brain activation during hand-action observation and dynamic-object observation. Results demonstrated that, compared with dynamic-object observation, hand-action observation led to greater performance with respect to the aphasia quotient and affiliated naming sub-tests and a greater western Aphasia Battery test score. The overall effect was similar to that of conventional aphasia training, yet hand-action observation had advantages compared with conventional training in terms of vocabulary extraction and spontaneous speech. Thus, hand-action observation appears to more strongly activate the mirror neuron system compared with dynamic-object observation. The activated areas included Broca's area, Wernicke's area, and the supramarginal gyrus. These results suggest that hand-action observation combined with repetition might better improve language function in aphasia patients compared with dynamic-object observation combined with repe

关键词： nerve regeneration mirror neuron hand-action observation aphasia rehabilitation stroke functional magnetic resonance imaging neuropsychology neural regeneration

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Progress in clinical trials of stem cell therapy for cerebral palsy

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Neural Regeneration research 2021年第7期16卷 1377-1382页

作者： Zhong-Yue Lv Ying Li Jing Liu Stem Cell Clinical research Center National Joint Engineering LaboratoryRegenerative Medicine CenterThe First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina dalian Innovation institute of Stem Cell and Precision medicine DalianLiaoning ProvinceChina

Cerebral palsy is the most common disease in children associated with lifelong disability in many *** research has demonstrated that traditional physiotherapy and rehabilitation therapies cannot alone cure cerebral *** cell transplantation is an emerging therapy that has been applied in clinical trials for a variety of neurological diseases because of the regenerative and unlimited proliferative capacity of stem *** this review, we summarize the design schemes and results of these clinical *** findings reveal great differences in population characteristics, stem cell types and doses, administration methods, and evaluation methods among the included clinical ***, we also assess the safety and efficacy of these clinical *** anticipate that our findings will advance the rational development of clinical trials of stem cell therapy for cerebral palsy and contribute to the clinical application of stem cells.

关键词： adverse events brain cell transplantation central nervous system cerebral palsy clinical trials plasticity regeneration stem cell

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Arenobufagin is a novel isoform-specific probe for sensing human sulfotransferase 2A1

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Acta Pharmaceutica Sinica B 2018年第5期8卷 784-794页

作者： Xiangge Tian Chao Wang Peipei Dong Yue An Xinyu Zhao Weiru Jiang Gang Wang Jie Hou Lei Feng Yan Wang Guangbo Ge Xiaokui Huo Jing Ning Xiaochi Ma Academy of Integrative medicine College of Pharmacy College of Basic Medical Science Second Affliated Hospital Dalian Medical University institute of Functional Materials and Molecular Imaging College of Emergency and Trauma Hainan Medical University institute of Functional Materials and Molecular Imaging College of Emergency and Traum1 Hainan Medical University Shanghai university of traditional Chinese medicine

Human cytosolic sulfotransferase 2 A1(SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin(AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as *** sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by in vitro reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals.

关键词： Sulfotransferase 2A1 Sulfation Arenobufagin Probe Selective substrate

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Met-Controlled Allosteric Module of Neural Generation as A New Therapeutic Target in Rodent Brain Ischemia

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Chinese Journal of Integrative medicine 2021年第12期27卷 896-904页

作者： LI Kang-ning ZHANG Ying-ying YU Ya-nan WU Hong-li WANG Zhong Department of traditional Chinese medicine Beijing Tiantan HospitalCapital Medical UniversityBeijing(100070)China institute of Basic research in Clinical medicine China Academy of Chinese Medical SciencesBeijing(100700)China

Objective To investigate a Met-controlled allosteric module(AM)of neural generation as a potential therapeutic target for brain *** We selected Markov clustering algorithm(MCL)to mine functional modules in the related target *** to the topological similarity,one functional module was predicted in the modules of baicalin(BA),jasminoidin(JA),cholic acid(CA),compared with I/R model *** functional module included three genes:Inppl1,Met and Dapk3(IMD).By gene ontology enrichment analysis,biological process related to this functional module was *** functional module participated in generation of *** blotting was applied to present the compound-dependent regulation of ***-immunoprecipitation was used to reveal the relationship among the three *** used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion *** expressions of vascular endothelial growth factor(VEGF)and matrix metalloproteinase 9(MMP-9)were supposed to show the changing circumstances for neural generation under cerebral *** Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group(P<0.05).Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory *** anti-ischemic excitatory allosteric module(AME)of generation of neurons(AME-GN)was validated successfully in *** neurons increased in BJC treatment group(P<0.05).The expression of VEGF and MMP-9 decreased in the compound treatment groups compared with the I/R model group(P<0.05).Conclusions AME demonstrates effectiveness of our pioneering approach to the discovery of therapeutic *** novel approach for AM discovery in an effort to identify therapeutic targets holds the promise of accelerating elucidation of underlying pharmacological mechanisms in cere

关键词： allosteric module InppM-Met-Dapk3 generation of neurons brain ischemia

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