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Role of epithelial-to-mesenchymal transition in the pulmonary fi brosis induced by paraquat in rats

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World Journal of Emergency Medicine 2021年第3期12卷 214-220页

作者： Jian-hua Yi Zhao-cai Zhang Mei-bian Zhang Xin He Hao-ran Lin Hai-wen Huang Hai-bin Dai Yu-wen Huang Emergency department the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Scientifi c Research department the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou 301051China Shangyu People’s Hospital Shaoxing 312300China pharmacy department the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China

BACKGROUND:This study aims to explore the characteristics of the epithelial-to-mesenchymal transition(EMT)process and its underlying molecular mechanisms in the period of paraquat(PQ)-induced pulmonary fi brosis(PF).METHODS:Picrosirius red staining and collagen volume fraction were utilized to evaluate the pathological changes of PQ-induced PF in rats.Immunohistochemistry,Western blot,and real-time reverse transcriptase-polymerase chain reaction(RT-PCR)were used to measure the protein and gene expression of EMT markers,EMT-associated transcription factors,and regulators of EMT-related pathways,respectively.RESULTS:The collagen deposition in the alveolar septum and increased PF markers were characteristics of pathological changes in PQ-induced PF,reached a peak on day 14 after PQ poisoning,and then decreased on day 21.The protein and gene expression of the fibrosis marker,EMT markers,transcription factors,and regulators of EMT-related signaling pathways signifi cantly increased at diff erent time points after PQ poisoning compared with corresponding controls(P0.05).CONCLUSIONS:EMT process plays a role in the PQ-induced PF,in which most PF and EMT markers have a peak phenomenon,and its underlying molecular mechanisms might be determined by further studies.

关键词： Pulmonary fibrosis Paraquat Epithelial-to-mesenchymal transition Rats

Advances on marine-derived natural radioprotection compounds:historic development and future perspective

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Marine Life Science & Technology 2021年第4期3卷 474-487页

作者： Reinu E.Abraham Mousa Alghazwi Qi Liang Wei Zhang Centre for Marine Bioproducts Development College of Medicine and Public HealthFlinders UniversityBedford ParkSA 5042Australia department of Pharmaceutical Sciences College of Clinical PharmacyKing Faisal UniversityAI-AhsaKingdom of Saudi Arabia Shanxi University of Traditional Chinese Medicine Taiyuan 030619China

Natural extracts and compounds from marine resources have gained intensive scientific and industry attention for radio-protective activities in the past ten years.However,the marine-derived radioprotectants have been studied against UV-rays,gamma(y)-rays and X-rays for more than 30 years.This review aims to identify key marine-derived extracts/compounds and their modes of action studied for radioprotective activities from 1986 to 2019.A comprehensive survey was conducted to establish the trend in terms of the publications each year and the countries of origin.A total of 40 extracts and 34 natural compounds showing radioprotective activities against UV-rays,gamma(y)-rays and X-rays were identified from a range of marine plants and animals.These extracts and compounds are broadly categorized into polysaccharides,phlorotannins,carotenoids and mycosporine-like amino acids(MAAs).Macroalgae and microalgae were found to be the dominant sources of polysaccharides,phlorotannins and carotenoids.MAAs were mainly identified in algae,sponges,sea cucumber and corals that showed significant UV-absorbing activities.A number of radioprotective mechanisms were shown by these compounds,predominantly free radicals scavenging,inhibition of apoptosis,UV-ray absorption and DNA damage-repair signaling pathways.While these bio-discoveries warrant further investigation and development of radioprotective therapeutics,however,the lack of clinical studies is a major obstacle to be tackled in the future.

关键词： Radio-protective Therapeutics Natural compounds Macro/microalgae Marine organisms Mechanism

Wheat ear carbon assimilation and nitrogen remobilization contribute significantly to grain yield

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Journal of Integrative Plant Biology 2016年第11期58卷 914-926页

作者： Bangwei Zhou Maria Dolores Serret Abdelhalim Elazab Jordi Bort Pie José Luis Araus Iker Aranjuelo álvaro Sanz-Sáez Key Laboratory of Vegetation Ecology Ministry of EducationInstitute of Grassland ScienceNortheast Normal University Unit of Plant Physiology Faculty of BiologyUniversity of Barcelona Agrobiotechnology Institute Public University of Navarra-CSIC-Navarra GovernmentArrosadia Campus department of Plant Biology University of the Basque Country Pharmacy Faculty

The role of wheat ears as a source of nitrogen （N） and carbon （C） in the grain filling process has barely been studied. To resolve this question, five wheat genotypes were labeled with 15N-enriched nutrient solution. N remobilization and absorption were estimated via the nitrogen isotope composition of total organic matter and Rubisco. Gas exchange analyses showed that ear photosynthesis contributed substantially to grain filling in spite of the great loss of C due to respiration. Of the total kernel N, 64.7% was derived from the N acquired between sowing and anthesis, while the remaining 35.3% was derived from the N acquired between anthesis and maturity. In addition, 1.87 times more N was remobilized to the developing kernel from the ear than from the flag leaf. The higher yielding genotypes showed an increased N remobflization to the kernel compared to the lower yielding genotypes. In addition, the higher yielding genotypes remobilized more N from the ears to the kernel than the lower yielding genotypes, while the lower yielding genotypes remobilized more N from the flag leaf to the kernel. Therefore, the ears contribute significantly toward fulfilling C and N demands during grain filling.

关键词： Carbon accumulation ear grain yield nitrogenaccumulation Rubisco

Recent trends and developments in the asymmetric synthesis of profens

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绿色合成与催化(英文)

绿色合成与催化(英文) 2023年第2期4卷 89-103页

作者： Qiuyue Wang Yuchen Qi Xuefeng Gao Lili Gong Ruiying Wan Weihua Lei Zhenguo Wang Jianyou Mao Haixing Guan Wei Li Patrick J.Walsh College of pharmacy Shandong University of Traditional Chinese MedicineJinan 250355China Experimental Center Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic ResearchShandong University of Traditional Chinese MedicineJinan 250355China department of Emergency Medicine People's Hospital of Huimin CountyBinzhou 251700China Technical Institute of Fluorochemistry Institute of Advanced SynthesisSchool of Chemistry and Molecular EngineeringNanjing Tech UniversityNanjing 211816China Roy and Diana Vagelos Laboratories Department of ChemistryUniversity of PennsylvaniaPhiladelphia 19104-6323United States

The profens belong to a class of nonsteroidal anti-inflammatory drugs(NSAIDs),which exert significant antiinflammatory,analgesic,antipyretic and other pharmacological effects.A considerable number of catalytic asymmetric strategies for the synthesis of enantioenriched profens have been introduced.Herein are outlined recent trends and developments of promising catalytic enantioselective systems for the generation of profens and their derivatives.According to the reaction type,we divided these transformations into three categories:Transition metal-catalyzed asymmetric hydrogenations,transition metal-catalyzed asymmetric cross-couplings and organocatalytic asymmetric transformations.Overviews of generic reaction mechanisms are presented.Ideally,this tutorial review will motivate further interest in the catalytic asymmetric synthesis of highly enantioenriched profens.

关键词： NSAIDs Asymmetric synthesis Transition metal catalysis Organocatalysis

Molecular Dynamics Simulation of the Binding Interaction between Hormone Glucagon Protein and Self-Assembled Monolayer Molecules

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Chinese Journal of Chemistry 2007年第8期25卷 1090-1093页

作者：王焰增陈正隆石玉清甘恒全陈昶宏胡举军苏致远 National Center for High-Performance Computing Tainan742 Taiwan China department of Chemistry National Sun Yat-Sen University Kaohsiung 804 Taiwan China department of lnformation Management SHU-TE University Kaohsiung 804 Taiwan China department oflnformation Management Chia Nan University of pharmacy & Science Tainan 717 Taiwan China

Restrained molecular dynamics simulations were performed to study the binding affinity of the peptide with alkanethiols of different tail-groups, S（CH2）7CH3, S（CH2）7OH and S（CH2）7COOH, which self-assembled on Au（111） surface in the presence of water molecules. The curves of binding affinity were calculated by fixing the center of mass of the peptide at various distances from the assembling surface. Simulation results show that the binding affin- ity is in the order as COOH-SAMs〉OH-SAMs〉CH3-SAMs, while 100% COOH-SAMs〉5% COOH-SAMS in concentration. The effects on binding affinity by different tail-groups were also studied. Results show that the binding affinity between COOH-SAMs and the peptide is bigger than those of the others and increasing the acidity of COOH-SAMs will result in stronger attractive power.

关键词： alkanethiol binding affinity molecular dynamics simulations self-assembled monolayer

Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2751-2777页

作者： Yurong Lai Xiaoyan Chu Li Di Wei Gao Yingying Guo Xingrong Liu Chuang Lu Jialin Mao Hong Shen Huaping Tang Cindy Q.Xia Lei Zhang Xinxin Ding Drug Metabolism Gilead Sciences Inc.Foster CityCA 94404USA department of Pharmacokinetics Pharmacodynamics and Drug MetabolismMerck&Co.Inc.KenilworthNJ 07033USA Pharmacokinetics Dynamics and MetabolismPﬁzer Worldwide Research and DevelopmentGrotonCT 06340USA Eli Lilly and Company IndianapolisIN 46221USA Drug Metabolism and Pharmacokinetics BiogenCambridgeMA 02142USA Drug Metabolism and Pharmacokinetics Accent TherapeuticsInc.LexingtonMA 02421USA department of Drug Metabolism and Pharmacokinetics GenentechA Member of the Roche GroupSouth San FranciscoCA 94080USA Drug Metabolism and Pharmacokinetics department Bristol-Myers Squibb CompanyPrincetonNJ 08540USA Bioanalysis and Biomarkers Glaxo Smith KlineKing of the PrussiaPA 19406USA department of Drug Metabolism and Pharmacokinetics Takeda Pharmaceuticals International Co.CambridgeMA 02139USA Ofﬁce of Research and Standards Ofﬁce of Generic DrugsCDERFDASilver SpringMD 20993USA department of Pharmacology and Toxicology College of PharmacyUniversity of ArizonaTucsonAZ 85721USA Current afﬁliation:Translational Medicine EMD Serono Research&Development InstituteInc.BillericaMA 01821USA Current afﬁliation:Drug Metabolism Gilead Sciences Inc.Foster CityCA 94404USA

Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

关键词： Drug discovery and development New drug application Biologics license application Pharmacokinetics ADME New modalities Model-informed drug development Micro-physiological systems

Antidepressant-Like Activity of Methanolic Extract of the Seeds of <i>Trachysperum ammi</i>in Swiss Albino Mice

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Pharmacology & pharmacy 2018年第12期9卷 503-514页

作者： Md. Rashidur Rahman Mohammad Ali Mostakim Sharif Sadiur Rahman Sajon Md. Abdul Mannan Md. Shahed-Al-Mahmud department of pharmacy Jessore University of Science and Technology Jessore Bangladesh department of pharmacy Stamford University Bangladesh Dhaka Bangladesh department of Microbiology and Immunology School of Medicine Tzu Chi University Hualian Taiwan

Trachysperum ammi has been traditionally used for the treatment of neurological disorders such as depression and anxiety. To date, T. ammi has reported for its chemical constituents in different diseases condition. The traditional evidence convinced us to perform the antidepressant-like activity of methanolic extract of Trachysperum ammi (META). The antidepressant activity of META assessed by using forced swimming test (FST), tail suspension test (TST), and locomotor activity test. The seed parts of META at doses level of 50, 100 and 200 mg/kg body weight administered orally to examine the CNS stimulants activity test in mice behavioral models. Here, we reported that META significantly reduced immobility time in the FST after repeated administration of 50, 100 and 200 mg/kg to mice for 14 days. The intensity of immobility significantly reduced at all of the doses (p < 0.05) whereas, we were found the strongest effect observed at 200 mg/kg. The antidepressant-like effect of META caused the reduction (p < 0.05) in the immobility in TST of mice when orally administered with 50, 100 and 200 mg/kg for 14 days, respectively. Additionally, we were executed locomotor activity test to check the motor stimulating activity. META has employed at a dosage of 50, 100 and 200 mg/kg for 14 days, the results have found that 50 mg/kg produced the locomotion effects as similar to the control group. Interestingly, the locomotion, rearing, and defecation significantly (p < 0.05) increased at the dosage of 100 and 200 mg/kg of META. Our present findings suggest that the seed parts of Trachysperum ammi may possess antidepressant-like activity which may use as a supportive treatment to management of neurological disorders.

关键词： Trachysperum ammi Antidepressant CNS Stimulants Forced Swimming

Protein-protein interaction map is a key gateway into liver regeneration

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World Journal of Gastroenterology 2010年第28期16卷 3491-3498页

作者： Chao Xie Run-Zhi Zhu Yun-Sheng Yuan Hong-Lin He Yan Yu Chao Xie Qiu-Shi Huang Jin Gao Wei Han School of Agriculture and Biology Shanghai Municipality Key Laboratory of Veterinary Biotechnology Shanghai Jiao Tong University Shanghai 200240 China department of Food Science Cornell University Ithaca NY 14853 United States Laboratory of Regeneromics School of pharmacy Shanghai Jiao Tong UniversityShanghai 200240 China

Recent studies indicate that the process of liver regeneration involves multiple signaling pathways and a variety of genes,cytokines and growth factors. Protein-protein interactions(PPIs)play a role in nearly all events that take place within the cell and PPI maps should be helpful in further understanding the process of liver regeneration.In this review,we discuss recent progress in understanding the PPIs that occur during liver regeneration especially those in the transforming growth factorβsignaling pathways.We believe the use of large-scale PPI maps for integrating the information already known about the liver regeneration is a useful approach in understanding liver regeneration from the standpoint of systems biology.

关键词： Liver regeneration Protein-protein interaction Protein-protein interaction maps Transforming growth factorβ

Synthesis of hollow and mesoporous structured NaYF4：Yb,Er upconversion luminescent nanoparticles for targeted drug delivery

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Journal of Rare Earths 2017年第5期35卷 419-429页

作者：梁旭华樊君王永波赵艳艳靳如意孙涛程敏王学军 College of Biology pharmacy and Food Engineering Shangluo University School of Chemical Engineering Northwest University School of Chemistry &Chemical Engineering Nanjing University

In this paper, we demonstrated a one-step template-free strategy to fabricate a hollow mesoporous structured NaY F4：Yb,Er nanoparticles with excellent upconversion luminescence. Folic acid（FA）, a commonly used cancer-targeting agent, was conjugated on the surface of the nanoparticles based on the presence of free amine groups, which were labeled as NaY F4：Yb,Er-FA HMUCNPs. The properties were extensively studied, which indicated the obtained samples showed a typical hollow mesoporous structure and excellent upconversion luminescence that were useful for cell imaging and drug delivery. The L929 cells viability, hemolysis assay and coagulation test demonstrated good biocompatibility of the samples. The anti-cancer drug doxorubicin hydrochloride（DOX） storage/release properties were demonstrated to be pH-responsive, in which, the drug release might be beneficial at the reduced pH for targeted release and controlled therapy. Moreover, it was found that DOX-loaded NaY F4：Yb,Er-FA HMUCNPs exhibited greater cytotoxicity to KB cells than free DOX due to the specific cell uptake by KB cells via folate receptor-mediate endocytosis. Therefore, the multifunctional nanoparticles combining upconversion luminescent property and hollow mesoporous structure have potential for simultaneous targeted anti-cancer drug delivery and cell imaging.

关键词： hollow luminescent structured template luminescence targeted fabricate loaded coagulation conjugated