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Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2992-3008页

作者： Shicheng Fan Yue Gao Pengfei Zhao Guomin Xie Yanying Zhou Xiao Yang Xuan Li Shuaishuai Zhang Frank JGonzalez Aijuan Qu Min Huangb Huichang Bi NMPA key laboratory for Research and Evaluation of drug Metabolism&Guangdong Provincial key laboratory of New drug Screening&Guangdong-Hongkong-Macao Joint laboratory for New drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Provincial key laboratory of New drug Design and Evaluation School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China laboratory of Metabolism Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA The State key laboratory of Chemical Oncogenomics School of Chemical Biology and BiotechnologyShenzhen Graduate School of Peking UniversityShenzhen 518055China

Fenofibrate,a peroxisome proliferator-activated receptor α(PPARα)agonist,is widely prescribed for hyperlipidemia *** studies also showed that it has therapeutic potential in various liver ***,its effects on hepatomegaly and liver regeneration and the involved mechanisms remain ***,the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice,which was dependent on hepatocyteexpressed PPARα.Yes-associated protein(YAP)is pivotal in manipulating liver growth and *** further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination,promoting its K63-linked ubiquitination,and enhancing the interaction and transcriptional activity of the YAP-TEAD *** inhibition of YAP-TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced *** factors,such as MYC,KRT23,RAS,and RHOA,might also participate in fenofibrate-promoted hepatomegaly and liver *** studies demonstrate that fenofibratepromoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling,with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.

关键词： Fenofibrate PPARa Hepatomegaly Partial hepatectomy Liver regeneration YAP TEAD Ubiquitination

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Mild construction of N-fused polycyclic compounds via Rh(Ⅲ)/EosinY co-catalyze C—H activation

Green Synthesis and Catalysis

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Green Synthesis and Catalysis 2024年第2期5卷 108-111页

作者： Zhouping Wu Guanghui Lv Zheng Lin Jiangyan Tang Jian Chen Jianghong Liu Li Hai Yong Wu key laboratory of drug-Targeting and drug delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Department of Pharmacy Taihe HospitalHubei University of MedicineNo.32 South Renmin RoadShiyan 442000China

The construction of N-fused polycyclic compounds at room temperature via the combination of transition-metal catalyst and photocatalyst has been *** novel work has successfully realized LED irradiated C—H activation of iodonium *** strategy shows wide substrate scope and ideal functional group *** work would be useful for the construction of various heterocyclic compounds.

关键词： N-fused polycyclic compounds C—H activation Rh(Ⅲ)catalyst and photocatalyst Iodonium ylides Energy transfer process

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The age of vanadium-based nanozymes: Synthesis, catalytic mechanisms, regulation and biomedical applications

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Chinese Chemical Letters 2024年第4期35卷 52-60页

作者： Shuaiwen Li Zihui Chen Feng Yang Wanqing Yue Department of Chemistry Key Laboratory of Biomedical Functional MaterialsSchool of ScienceChina Pharmaceutical UniversityNanjing 211198China key laboratory of drug Quality Control and Pharmacovigilance(China Pharmaceutical University) Ministry of EducationNanjing 211198China

Nanomaterials with enzyme-mimic(nanozyme) activity have garnered considerable attention as a potential alternative to natural enzymes, thanks to their low preparation cost, high activity, ease of preservation, and unique physicochemical properties. Vanadium(V) is a transition metal that integrates the benefits of valence-richness, low cost, and non-toxicity, making it a desirable candidate for developing a range of emerging nanozymes. In this review, we provide the first systematic summary of recent research progress on V-based nanozymes. First, we summarize the preparation of V-based nanozymes using both top-down and bottom-up synthesis methods. Next, we review the mechanism of V-based nanozymes that mimic the activity of various enzymes. We then discuss methods for regulating V-based nanozyme activity, including morphology, size, valence engineering, defect engineering, external triggering, and surface engineering. Afterward, we outline various biomedical applications, including therapeutic, anti-inflammatory, antibacterial, and biosensing. Finally, we prospect the challenges and countermeasures for V-based nanozymes based on their development. By summarizing recent research progress on V-based nanozymes, we hope to provide useful insights for researchers to further explore their potential applications and overcome their existing challenges.

关键词： Vanadium Nanozymes Catalytic mechanisms Biomedical applications Regulation

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Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis

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Chinese Chemical Letters 2024年第6期35卷 462-468页

作者： Yu Yan Jiawei Song Dongdong Liu Zihan Liu Jialing Cheng Zhiyang Chen Yanfang Yang Weizhe Jiang Hongliang Wang Jun Ye Yuling Liu State key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China College of Pharmacy Guangxi Medical UniversityNanning 530021China Beijing key laboratory of drug delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal *** mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes *** evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in ***,the treatment of UC faces challenges due to low drug delivery efficiency and short retention *** overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and *** thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 *** a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal *** of UC were markedly reduced following rectal administration of SZ-A thermosensitive ***,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel *** integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive *** conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal *** approach holds promise as a potential treatment for UC.

关键词： Ulcerative colitis SZ-A Thermo-sensitive hydrogel Rectal administration Alleviation of inflammation Mucosal barrier repair

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Paclitaxel-lipid prodrug liposomes for improved drug delivery and breast carcinoma therapy

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Chinese Chemical Letters 2024年第2期35卷 335-340页

作者： Xin Wu Xinmei Chen Xinyu Wang Haisheng He Jianming Chen Wei Wu key laboratory of Smart drug delivery of MOE School of PharmacyFudan UniversityShanghai 201203China Department of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Shanghai Wei Er Lab Shanghai 201707China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor *** are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’tolerance owing to excellent biocompatibility and ***,poor compatibility between PTX and liposomes compromises the stability,drug loading and anti-tumor capacity of liposomal *** address this issue,three lipids with various chain lengths,namely,myristic acid(MA,14C),palmitic acid(PA,16C)and stearic acid(SA,18C),were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes,*** liposomes show high stability and drug loadings,as well as sustained drug *** chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates,which further impact the pharmacokinetics,tumor accumulation,and anti-tumor efficacy of liposomal *** rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of *** all liposomes,PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo,owing to its moderate drug release and enzymatic conversion *** its superior safety,PTX-PA liposomes hold potential for further clinical translation.

关键词： Paclitaxel Lipids Prodrugs Liposomes drug release Chemotherapy

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A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1827-1844页

作者： Zinan Zhang Wenbin Cao Huanchun Xing Shuai Guo Lijuan Huang Lin Wang Xin Sui Kui Lu Yuan Luo Yongan Wang Jun Yang State key laboratory of Toxicology and Medical Countermeasures Beijing Institutes of Pharmacology and ToxicologyBeijing 100850China tianjin University of Science and Technology Tianjin 300222China Hebei University of Science and Technology Shijiazhuang 050018China

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be *** this study,we propose a brain-targeted delivery strat-egy based on selective opening of the *** strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing *** on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain *** an effective dose,this delivery system is safe,especially with its effect on the BBB being *** mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

关键词： Liposomes Phospholipase A2 Phosphoserine Blood-brainbarrier Selectively open Mix&act

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Total Synthesis of Laurane and Guaiane Sesquiterpenoids via Oxidative Nazarov Reaction

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Chinese Journal of Chemistry 2024年第11期42卷 1267-1274页

作者： Yuye Chen Wenqing Chen Zhiting Zhang Jing Xu Shenzhen Grubbs Institute and Department of Chemistry and Guangming Advanced Research Institute and Guangdong Provincial key laboratory of Catalysis and Shenzhen key laboratory of Small Molecule drug Discovery and Synthesis Southern University of Science and TechnologyShenzhenGuangdong518055 China

As one of the most common structural motifs in natural products,cyclopentenones usually can be fabricated by Nazarov cyclization using divinyl ketones or functionalized tertiary divinyl carbinols(TDCs)as ***,straightforward method for transforming unfunctionalized TDCs to their corresponding cyclopentenones is currently ***,we wish to report the total syntheses of four structurally distinct terpenoids,namely laurane-type marine sesquiterpenoids isolaurene,debromoaplysin and aplysin,and guaiane sesquiterpenoid guaiadienone A,all using a novel synthetic method,named oxidative Nazarov cyclization,as the key *** work demonstrated our robust method is suitable for synthesizing various highly substituted cyclopentenones.

关键词： Total synthesis Synthetic methods Sesquiterpenoids Oxidative Nazarov reaction Electrocyclization Oxoammonium salt Pericyclic reaction Annulation

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Bimetallic nanoparticles as cascade sensitizing amplifiers for low-dose and robust cancer radio-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1787-1800页

作者： Yupeng Wang Lina Wang Tao Li Min Ouyang Hejian Xiong Dongfang Zhou Department of Ultrasonic Diagnosis Zhujiang HospitalKey Laboratory of Mental Health of the Ministry of EducationNMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Testing and Analysis Center Hebei Normal UniversityShijiazhuang 050024China Department of Mechanical Engineering The University of Texas at DallasRichardsonTX 75080USA

Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant *** particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent ***-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of ***,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust *** OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor *** cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune *** a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal ***,a long-term immunological memory effect to protect mice from tumor rechal-lenging is ***,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.

关键词： Bimetallic nanoparticles Radio-immunotherapy Cascade sensitizing amplifier,Oxaliplatin Fenton-typeHaber-Weiss reaction Radiosensitization Immunogenic cell death Radio-resistance

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Zinc(II)metal-organic framework eluting titanium implant as propulsive agent to boost the endothelium regeneration

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Frontiers of Chemical Science and Engineering 2024年第6期18卷 123-131页

作者： Wen Liu Xiaoyu Wang Ying Li Shihai Xia Wencheng Zhang Yakai Feng School of Chemical Engineering and Technology Tianjin UniversityTianjin 300350China College of Materials Science and Engineering Qingdao UniversityQingdao 266071China Department of Hepatopancreatobiliary and Splenic Medicine Affiliated HospitalLogistics University of People’s Armed Police ForceTianjin 300162China Department of Physiology and Pathophysiology Logistics University of Chinese People’s Armed Police ForceTianjin 300309China Frontiers Science Center for Synthetic Biology Tianjin UniversityTianjin 300072China key laboratory of Systems Bioengineering(Ministry of Education) Tianjin UniversityTianjin 300072China

The advent of antiproliferative drug-eluting vascular stents can dramatically reduce in-stent restenosis via inhibiting the hyperproliferation of vascular smooth muscle ***,the antiproliferative drugs also restrain the repair of the injured endothelial layer,which in turn leads to the very later in-stent *** points that competent endothelium plays a critical role in guaranteeing the long-term patency via maintaining vascular *** the regeneration of endothelium on the implanted vascular stents could be rendered as a promising strategy to reduce stent implantation *** this regard,bioactive zinc(II)metal-organic framework modified with endothelial cell-targeting Arg-Glu-Asp-Val peptide was embedded in poly(lactide-co-caprolactone)to serve as a functional coating on the surface of titanium substrate,which can promote the proliferation and migration of endothelial *** in vitro cell experiments revealed that the zinc(II)metal-organic framework embedded in the polymer coating was able to modulate the behaviors of endothelial cells owing to the bioactive effects of zinc ion and *** results confirmed that zinc(II)metal-organic framework eluting coating represented a new possibility for promoting the repair of the damaged endothelium with potential clinical implications in vascular-related biomaterials and tissue engineering applications.

关键词： Zinc(II)metal-organic framework vascular stent REDV peptide endothelium regeneration coating

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Theoretical and experimental cocrystal screening of temozolomide with a series of phenolic acids, promising cocrystal coformers

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Chinese Chemical Letters 2024年第5期35卷 407-417页

作者： Hongmei Yu Baoxi Zhang Meiju Liu Cheng Xing Guorong He Li Zhang Ningbo Gong Yang Lu Guanhua Du Beijing key laboratory of Polymorphic drugs Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing City key laboratory of drug Target Identification and drug Screening Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

The virtual cocrystal screening approach based on molecular electrostatic potential surface(MEPS)maps is a fast and feasible computational method to estimate the probability of cocrystal formation by calculating the difference in the interaction site pairing energies of monomers and that of their assemblies prior to experimental *** this paper,we report 12 cocrystal forms of temozolomide with mono-,di-,and trihydroxy benzoic acids,namely,3-hydroxy-,2,4-dihydroxy-,2,5-dihydroxy-,2,6-dihydroxy-,3,4-dihydroxy-,and 3,4,5-trihydroxy-benzoic acids,as well as benzoic acid,as pharmaceutical coformers for the first time.10 single crystals out of the 12 cocrystal forms were obtained and unequivocally determined by single-crystal X-ray diffraction,which clarified spatial arrangements,molecular conformations,and supramolecular *** further gains some insights into the sites of hydrogen bonding interactions for exploring combination patterns in these *** stability of TMZ was successfully achieved by cocrystallization with these acids.

关键词： Virtual Cocrystal Temozolomide Supramolecular synthon Phenolic acid Stability

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