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Enhanced homing of mesenchymal stem cells for in situ niche remodeling and bone regeneration

Nano Research 2024年第8期17卷 7449-7460页

作者： Yin Yuan Lijun Chen Jing Yang Sining Zhou Yangxin Fang Qi Zhang Ning Zhang Yifei Li Li Yuan Fan Jia Shuo Ni Charlie Xiang State key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Biology The David H.Koch Institute for Integrative Cancer Research at MITMassachusetts Institute of TechnologyCambridgeMA 02139USA Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China Innovative Precision Medicine(IPM)Group Hangzhou 311215China MOE key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of Cancer Immunology and Virology Dana-Farber Cancer InstituteBostonMA 02215USADepartment of ImmunologyHarvard Medical SchoolBoston MA 02115USA Department of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200233China

Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis ***,limited sources and poor tissue-homing efficiency limit their clinical *** this study,we isolated a kind of MSCs from women’s menstrual blood(MenSCs)noninvasively and established a novel MSCs bone marrow-targeted delivery system by utilizing waterin-oil-in-water droplet *** were encapsulated withinβ-cyclodextrin-functionalized alginate microcapsules loaded with zoledronates,which has a high affinity for *** this delivery system,MenSCs could be preferentially delivered to the bone marrow tissues via intravenous infusion,and restored bone mass by remodeling the bone marrow niche in situ in ovariectomized mouse ***,scRNA-seq analysis demonstrated that those MenSCs homed to the bone marrow recruited CD4^(+)FOXP3^(+)natural regulatory T(nT_(reg))cells by secreting *** recruited nTreg promoted CD8^(+)T cells to secret Wnt family member 10B(WNT10B),activating the Wnt signaling in osteoblasts and thus promoting bone formation in situ in the bone *** study reveals a promising application of MenSCs in postmenopausal osteoporosis treatment and highlights the clinical value of MenSCs by encouraging women to reserve autologous MenSCs before menopause to prevent and alleviate postmenopausal osteoporosis.

关键词： mesenchymal stem cells microfluidics bone marrow homing stem cell niche postmenopausal osteoporosis

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Neutralization of SARS-CoV-2 infection by antibodies targeting diverse epitopes

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Genes & Diseases 2024年第4期11卷 134-137页

作者： Shusheng Wang Yunji Liao Kaiyong Yang Hang Ma Zhangyi Song Haiqiu Huang Li Zhang Ailing Wang Lei Han Jiawei Zhang Hui Chen Haiyang Yin Yantin Bian Hua Jiang Xiaodong Xiao Yueqing Xie Yunsheng Yuan Jianwei Zhu Engineering Research Center of Cell and Therapeutic Antibody Ministry of EducationSchool of PharmacyShanghai Jiao Tong UniversityShanghai 200240China Jecho Laboratories Inc.FrederickMD 21704USA Jecho Institute Co. Ltd.Shanghai 200240China

The CoVID-19 pandemic that started in late 2019 is sweeping through the world,posing historic challenges to global health,and disrupting social and economic *** and recent studies indicate that monoclonal antibodies can be efficacious in preventing and treating SARSCoV-1 and SARS-CoV-2 *** a phage display platform,we have identified dozens of monoclonal antibodies that bind to diverse epitope groups on the SARS-CoV-2 spike *** of them bound to the receptor binding domain(RBD)and inhibited ACE2-RBD interaction.

关键词： antibodies inhibited monoclonal

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A pilot study of the differentiated landscape of peripheral blood mononuclear cells from children with incomplete versus complete Kawasaki disease

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World Journal of Pediatrics 2024年第2期20卷 189-200页

作者： Shu-Na Sun Yan Zhou Xing Fu Yuan-Zheng Zheng Cao Xie Guo-You Qin Fang Liu Chen Chu Feng Wang Cheng-Long Liu Qing-Tong Zhou De-Hua Yang Di Zhu Ming-Wei Wang Yong-Hao Gui Children's Hospital of Fudan University National Children's Medical CenterShanghai 201102China The National Center for drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Accuramed Technology(Shanghai)Ltd. Shanghai 200233China School of Pharmacy Fudan UniversityShanghai 201203China School of Public Health Fudan UniversityShanghai 200032China Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China Research Center for Deepsea Bioresources Sanya 572025China Department of Chemistry School of ScienceThe University of TokyoTokyo 113-0033Japan School of Pharmacy Hainan Medical UniversityHaikou 570288China

Kawasaki disease(KD)is a disorder of immune *** prevalence of KD among 100,000 children aged 0-4 years was 71.9-110.0 in china,170.9-194.9 in Korea,and 18.1-21.3 in the USA[1].The most severe complication of KD is coronary artery lesions(CALs),including coronary dilatation and coronary aneurysms,which may even lead to myocardial ischemia,myocardial infarction,and sudden death.

关键词： coronary ischemia differentiated

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High expression of GPR160 in prostate cancer is unrelated to CARTp-mediated signaling pathways

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1467-1471页

作者： Chenyu Ye Qingtong Zhou Shi Lin Wensheng Yang Xiaoqing Cai Yiting Mai Yanyan Chen Dehua Yang Ming-Wei Wang Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China Research Center for Deepsea Bioresources Sanya 572025China Department of Pharmacy Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghai 201102China State key Laboratory of Chemical Biology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China The National Center for drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Department of Chemistry School of Sciencethe University of TokyoTokyo 113-0033Japan School of Pharmacy Hainan Medical UniversityHaikou 571199China

To the Editor:G protein-coupled receptors(GPCRs)are the largest group of membrane proteins with over 800 members,characteristic of a seven transmembrane *** playing crucial roles in regulation of various physiological processes,GPCRs have been implicated in many diseases including diabetes,obesity,depression and *** initiate different intracellular responses,GPCRs mainly interact with three families of effector proteins upon agonist binding:the heterotrimeric G proteins,G protein-coupled receptor kinases(GRKs)and arrestins1.

关键词： GPR160 CARTp Prostate cancer Signaling pathway

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Synthesis,pharmacokinetics and in vivo antifungal activity of the novel water-soluble prodrugs of itraconazole analogue YL-24

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Chinese Chemical Letters 2013年第4期24卷 321-324页

作者： Yu Liu Xu-Feng Cao Xin Liu Yong-Bing Cao Wen-Jing Chu Yu-She Yang State key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy Second Military Medical University State key Laboratory of drug Research Shanghai Institute of Materia MedicoChinese Academy of Sciences

To improve the aqueous solubility of an itraconazole analogue, compound 1 （YL-24）, a series of novel prodrugs were synthesized. Among these prodrugs, the phosphate disodium salt compound 7 exhibited excellent aqueous solubility （9.8 mg/mL） at near-neutral pH and sufficient stability in buffer solutions, along with favorable pharmacokinetic profiles. In particular, compounds 1 and 7 provided moderate survival efficacy in murine systemic Candida albicans SC5314 infection model, but their efficacy was weaker than that of fluconazole.

关键词： SynthesisAntifungalWater-soluble prodrugsltraconazole analogue

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Synthesis and antibacterial activity of pleuromutilin derivatives with novel C(14) side chain

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Chinese Chemical Letters 2012年第1期23卷 9-12页

作者： Li Qiang Fu Chen Yu Ling Xing Sheng Guo Hui Li He Yu She Yang Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China

In order to find novel antibacterial agents with superior antibacterial activity and overcoming multidrug resistance,a series of pleuromutilin derivatives with novel C（14） side chain were synthesized and evaluated for their in vitro antibacterial *** results of antibacterial acticities indicated that most of the derivatives showed potent activities against Gram-positive *** particular,compound lOd exhibited the most potent inhibitory activity compared with pleuromutilin and linezoid,emerged as potential molecule for further investigation.

关键词： Synthesis Pleuromutilin Novel side chains Antibacterial activity

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Design and synthesis of novel antifungal triazole derivatives with good activity and water solubility

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Chinese Chemical Letters 2013年第4期24卷 303-306页

作者： Xu-Feng Cao Wen-Jing Chu Yong-Bing Cao Yu-She Yang State key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy Second Military Medical University

In order to find novel antifungal agents with good activity and aqueous solubility, a series of SYN-2869 analogues containing a pyridine ring were synthesized and evaluated for their in vitro antifungal activity and water solubility. The results indicated that some compounds showed potent activity against six pathogenic fungi. In particular, the analogue 17a having an isobutyl substitution on the triazolone exhibited significant broad spectrum antifungal activity. In addition, the water solubility of compound l？a was sufficiently improved over SYN-2869.

关键词： SynthesisAntifungalSYN-2869 analoguesTriazoleWater solubility

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Design,synthesis and biological evaluation of LpxC inhibitors with novel hydrophilic terminus

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Chinese Chemical Letters 2015年第6期26卷 763-767页

作者： Shi Ding Wen-Ke Wang Qiao Cao Wen-Jing Chu Le-Fu Lan Wen-Hao Hu Yu-She Yang State key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences Shanghai Engineering Research Center of Molecular Therapeutics and new drug Development East China Normal University

In order to develop novel LpxC inhibitors with good activities and metabolic stability, two series of compounds with hydrophilic terminus have been synthesized and their in vitro antibacterial activities against Escherichial coil and Pseudomonas aemginosa were evaluated. Especially, compounds 22b and c exhibited comparable antibacterial activities to CHIR-090 and better metabolic stability than CHIR-090 and LPC-011 in liver microsomes （rat and mouse）, which indicated the terminal methylsulfone may be a preferred structure in the design of LpxC inhibitors and worthy of further investigations.

关键词： LpxC CHIR-090 Kojic acid derivatives Methylsulfone derivatives Metabolic stability

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Investigating design principles of micropatterned encapsulation systems containing high-density microtissue arrays

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Science china(Life Sciences) 2014年第2期57卷 221-231页

作者： JIANG LiYang LIU JiaYing WANG Kai GU Xi LUO Ying Department of Biomedical Engineering College of Engineering Peking University National Engineering Laboratory for Regenerative and Implantable Medical Devices

Immunoisolation is an important strategy to protect transplanted cells from rejection by the host immune ***,microfabrication techniques have been used to create hydrogel membranes to encapsulate microtissue in an arrayed *** method illustrates a new macroencapsulation paradigm that may allow transplantation of a large number of cells with microscale spatial control,while maintaining an encapsulation device that is easily maneuverable and remaining integrated following *** study aims to investigate the design principles that relate to the translational application of micropatterned encapsulation membranes,namely,the control over the transplantation density/quantity of arrayed microtissues and the fidelity of pre-formed microtissues to *** hydrogel membranes with microwell patterns were used as a model encapsulation system to exemplify these *** results show that high-density micropatterns can be generated in hydrogel membranes,which can potentially maximize the percentage volume of cellular content and thereby the transplantation efficiency of the encapsulation *** seeding of microtissues demonstrates that microwell structures can efficiently position and organize pre-formed microtissues,suggesting the capability of micropatterned devices for manipulation of cellular transplants at multicellular or tissue *** theoretical analysis was performed to provide insights into the relationship between micropatterns and the transplantation capacity of membrane-based *** study lays the ground for developing new macroencapsulation systems with microscale cellular/tissue patterns for regenerative transplantation.

关键词： hydrogel micropattern array multi-cellular spheroids macroencapsulation

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Inhaled curcumin mesoporous polydopamine nanoparticles against radiation pneumonitis

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2522-2532页

作者： Ting Chen Bo Zhuang Yueqi Huang Yan Liu Bochuan Yuan Wanmei Wang Tianyu Yuan Lina Du Yiguang Jin Guangdong Pharmaceutical University Guangzhou 510006China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Department of Chemical Defense Institute of NBC DefenseBeijing 102205China

Radiation therapy is an effective method to kill cancer cells and shrink tumors using highenergy X-ray or γ-ray. Radiation pneumonitis(RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here,we prepared curcumin-loaded mesoporous polydopamine nanoparticles(CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles(MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π-π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2 B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of15 Gy^(60)Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.

关键词： Radiation pneumonitis Curcumin Mesoporous Polydopamine Nanoparticle Pulmonary delivery Inhalation Free radical scavenging

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