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Cardiac fibroblast-specific expression of IL-37 confers the protective effects on fibrosis in diabetic cardiomyopathy mice by regulating SOCS3-STAT3 axis

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Journal of Geriatric Cardiology 2024年第11期21卷 1060-1070页

作者： Qing-Yu HUANG Jian LI Tong-Qing CHEN Yi-Ming WANG Xiao-Yan SHEN Hai-Ming SHI Xin-Ping LUO Bo JIN Yan YOU Bang-Wei WU department of Cardiology Huashan HospitalFudan UniversityShanghaiChina department of pharmacology&the Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghaiChina

Background Human interleukin(IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive *** has been demonstrated extensive beneficial effects on various diseases;however,its role in the pathogenesis of diabetic cardiomyopathy(DCM)remains *** In vivo,DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts(CFs)specific hIL-37b overexpression mice(IL-37-Tg).In vitro,primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic *** function of the mice was assessed using *** staining,immunofluorescence,western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related *** In this study,we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis,as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM *** beneficial effects of IL-37 were consistently observed in CFs treated with high glucose(HG)and palmitic acid(PA).Moreover,we also discovered that the presence of IL-37 increased the expression of SOCS3,a crucial regulator of JAK/STAT signaling,in DCM mice and HG and PA-treated ***,the anti-fibrotic action of IL-37 in HG and PAtreated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically *** Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.

关键词： SOCS3 STAT3 protective

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Efficacy of inverso isomer of CendR peptide on tumor tissue penetration

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Acta Pharmaceutica Sinica B 2018年第5期8卷 825-832页

作者： Ruifeng Wang Qing Shen Xue Li Cao Xie Weiyue Lu Songli Wang Jing Wang Dongli Wang Min Liu Key Laboratory of Smart Drug Delivery Ministry of Education Department of Pharmaceutics School of Pharmacy Fudan University

The dense extracellular matrix and high interstitial fluid pressure of tumor tissues prevent the ability of anti-tumor agents to penetrate deep into the tumor parenchyma for treatment effects. C-end rule(CendR) peptides can enhance the permeability of tumor blood vessels and tumor tissues via binding to neuropilin-1(NRP-1), thus aiding in drug delivery. In this study, we selected one of the CendR peptides(sequence RGERPPR) as the parent L-peptide and substituted D-amino acids for the L-amino acids to synthesize its inverso peptide D(RGERPPR). We investigated the NRP-1 binding activity and tumorpenetrating ability of D(RGERPPR). We found that the binding affinity of D(RGERPPR) with NRP-1 and the cellular uptake was significantly higher than that of RGERPPR. Evans Blue tests revealed that D(RGERPPR) exhibited improved tumor-penetrating ability in C6, U87 and A549 tumor-bearing nude mice. Using nude mice bearing A549 xenograft tumors as a model, we found that the rate of tumor growth in the group co-administered with D(RGERPPR) and gemcitabine(Gem) was significantly lower than the gemcitabine-treated group with a tumor suppression rate(TSR%) of 55.4%. Together, our results demonstrate that D(RGERPPR) is a potential tumor-penetrating peptide.

关键词： Inverso isomer CendR peptide Neuropilin-1(NRP-1) Tumor penetration Gemcitabine

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Drug targeting through platelet membrane-coated nanoparticles for the treatment of rheumatoid arthritis

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Nano Research 2018年第11期11卷 6086-6101页

作者： Yuwei He Ruixiang Li Jianming Liang Ying Zhu Shuya Zhang Zicong Zheng Jing Qin Zhiqing Pang Jianxin Wang department of Pharmaceutics School of Pharmacy Fudan University & Key Laboratory of Smart Drug Delivery Ministry of Education Shanghai 201203 China Institute of Clinical pharmacology Guangzhou University of Traditional Chinese Medicine Guangzhou 510006 China

The effective drug treatment of rheumatoid arthritis (RA) is hindered by poor delivery efficiency to the diseased site and the serious side effects caused by wide-spread drug distribution. Traditional drug-targeting strategies, such as ligand modification, are complex, laborious, and inefficient. Inspired by the intrinsic relationship between platelets and RA, platelet-mimetic nanoparticles (PNPs) were developed for targeted drug delivery in RA. Through platelet receptor-mediated adhesion, an intact platelet membrane was coated onto poly (lactic-co-glycolic acid) nanoparticles, endowing the resulting PNPs with various functional receptors. By coating with platelet membranes, the nanoparticles were stabilized and had a better circulation profile, providing a benefit for passive targeting. In vitro binding of PNPs to inflamed endothelium, and in vivo accumulation in joints of a collagen-induced arthritis (CIA) mouse model of RA were significantly improved via P-selectin and GVPI recognition, indicating that the PNPs could effectively target to RA tissues through multiple mechanisms, similar to natural platelets. Moreover, FK506, a model drug, was loaded into the PNPs and used to treat RA. Pharmacodynamic studies demonstrated that the FK506-PNPs had a notable anti-arthritic effect in CIA mice. This study provides a new biomimetic targeting strategy with great potential for the treatment of RA.

关键词： biomimetic nanoparticles platelet membrane rheumatoid arthritis targeted drug delivery

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Synthesis and Antibacterial Activities of Pyran Annulated Heterocyclic Compounds

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Chinese Journal of Structural Chemistry 2015年第2期34卷 185-188页

作者：曲迪刘振李靖罗晓星李明凯 department of pharmacology School of Pharmacythe Fourth Military Medical University school of Chemistry and Chemical Engineering Xi’an University

Two novel pyran annulated heterocyclic compounds （1 and 2） were synthesized and characterized via IR, lH NMR and H RMS. The structure of compound 1 was verified by single-crystal X-ray diffraction. The in vitro antibacterial activities of the two compounds against Staphylococcus aureus （S. aureus ATCC 29213）, methicillin-resistant S. aureus （MRSA XJ 75302）, vancomycin-intermediate S. aureus （Mu50 ATCC 700699）, and USA 300 （Los Angeles County clone, LAC） were evaluated by observing the minimum inhibitory concentration.

关键词： pyran, crystal, staphylococcus aureus, minimum inhibitory concentration

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Highlights for the 6th International Ion Channel Conference:ion channel structure,function,disease and therapeutics

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Acta Pharmaceutica Sinica B 2017年第6期7卷 665-669页

作者： Limei Wang Kewei Wang department of pharmacology Qingdao University School of PharmacyQingdao 266021China

To foster communication and interactions amongst international scholars and scientists in the field of ion channel research, the 6 th International Ion Channel Conference(IICC-2017) was held between June 23–27, 2017 in the eastern coastal city of Qingdao, China. The meeting consisted of 450 attendees and 130 speakers and poster presenters. The program consisted of research progress, new findings and ongoing studies that were focused on(1) Ion channel structure and function;(2) Ion channel physiology and human diseases;(3) Ion channels as targets for drug discovery;(4) Technological advances in ion channel research. An insightful overview was presented on the structure and function of the mechanotransduction channel Drosophila NOMPC(No mechanoreceptor potential C), a member of the transient receptor potential(TRP) channel family. Recent studies on Transmembrane protein 16 or Anoctamin-1(TMEM16A, a member of the calcium-activated chloride channel [CaCC] family) were summarized as well. In addition, topics for ion channel regulation, homeostatic feedback and brain disorders were thoroughly discussed. The presentations at the IICC-2017 offer new insights into our understanding of ion channel structures and functions, and ion channels as targets for drug discovery.

关键词： Ion channel Structure Function Channelopathy Drug target Mechanotransduction Voltage-gated Ca2+ channel Anoctamin-1 Calcium activated chloride channel M-type potassium channel GIRK channel Voltage-gated sodium channel

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Iron oxide nanoparticle-based theranostics for cancer imaging and therapy

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Frontiers of Chemical Science and Engineering 2014年第3期8卷 253-264页

作者： Xiaoqing REN Hongwei CHEN Victor YANG Duxin SUN department of Pharmaceutical Sciences College of Pharmacy University of Michigan Ann Arbor MI 48109 USA school of pharmacy Fudan University Shanghai 200433 China

Theranostic platform, which is equipped with both diagnostic and therapeutic functions, is a promising approach in cancer treatment. From various nanotheranostics studied, iron oxide nanoparticles have advantages since IONPs have good biocompatibility and spatial imaging capability. This review is focused on the IONP- based nanotheranostics for cancer imaging and treatment. The most recent progress for applications of IONP nanotheranostics is summarized, which includes IONP- based diagnosis, magnetic resonance imaging （MRI）, multimodal imaging, chemotherapy, hyperthermal therapy, photodynamic therapy, and gene delivery. Future perspectives and challenges are also outlined for the potential development of IONP based theranostics in clinical use.

关键词： theranostics iron oxide nanoparticles MRI,drug delivery photothermal therapy photodynamic therapy

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Studies on the anti-asthmatic and antitussive properties of aqueous leaf extract of Bryophyllum pinnatum in rodent species

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Asian Pacific Journal of Tropical Medicine 2013年第6期6卷 421-425页

作者： Edward O Salami Raymond I Ozolua Stephen O Okpo Gerald I Eze Dickson O Uwaya department of pharmacology and Toxicology Faculty of pharmacy University of Benin department of Anatomy School of Basic Medical SciencesUniversity of Benin department of pharmacology and Toxicology Faculty of PharmacyUniversity of Benin

Objective:To evaluate the antiasthmatic and antitussive properties of the aqueous leaf extract of Bryophyilum pinnatum {***)(BP) ***:Ovalbiunin-sensilized guinea pigs which were treated with BP for 21 consecutive days were exposed to 0.2%histamine aerosol in a glass *** viscosity,white blood cell and lymphocyte counts and tracheal wall morphometry were *** of cough were counted pre and post acute exposure of extract-treated(X7 d) guinea pigs to 7.5%citric acid aerosol in a *** red expectoration was estimated in mice after 7 d of daily administration of ***:Doses of 200 and 400 mg/kg/day(×21 d) BP significantly increased the time for guinea pigs to experience preconvulsive *** and salbutamol(0.5 mg/kg/day×21 d) reduced mucus viscosity in the sensitized group to values comparable with *** blood cell,lymphocyte counts and tracheal morphometry were not significantly *** doses of BP also significantly reduced the bouts of cough but only 400 mg/kg/day significantly inhibited the amount of phenol red ***:BP has demonstrated antiasthmatic and antitussive properties in these rodent *** properties may underscore its use in Nigerian ethnomedicine.

关键词： Bryophyllum pinnatum Antiasthmatic Antitussive Airway histology

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Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties:preparation, characterization and application in a vaginal drug delivery system

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Acta Pharmaceutica Sinica B 2017年第5期7卷 593-602页

作者： Liqian Ci Zhigang Huang Yu Liub Zhepeng Liu Gang Wei Weiyue Lu school of Medical Instrument and Food Engineering University of Shanghai for Science and Technology department of Pharmaceutics School of Pharmacy Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University)Ministry of Education

Lack of mucoadhesive properties is the major drawback to poloxamer 407(F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an aminofunctionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407(F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol(AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels(NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin wasrevealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.

关键词： Poloxamer 407 Amino group Acetate gossypol In situ hydrogel Mucoadhesive gel

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Charge-reversal nanoparticles: novel targeted drug delivery carriers

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Acta Pharmaceutica Sinica B 2016年第4期6卷 261-267页

作者： Xinli Chen Lisha Liu Chen Jiang Key Laboratory of Smart Drug Delivery Ministry of Education Department of PharmaceuticsSchool of Pharmacy Fudan University State Key Laboratory of Medical Neurobiology Fudan University

Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosagecontrolled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors(changes in p H,redox gradients, or enzyme concentration) or exogenous factors(light or thermos-stimulation).

关键词： Cancer therapy Charge-reversal nanoparticles Drug delivery carriers Stimuli responsive Nanotechnology

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Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cells via regulating cellular free fatty acid sensitivity

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3964-3982页

作者： Weilian Bao Jiaren Lyu Guize Feng Linfeng Guo Dian Zhao Keyuan You Yang Liu Haidong Li Peng Du Daofeng Chen Xiaoyan Shen department of pharmacology&the Key Laboratory of Smart Drug Delivery Ministry of Education School of PharmacyFudan UniversityShanghai 201210China department of Natural Medicine School of PharmacyFudan UniversityShanghai 201210China department of Colorectal and Anal Surgery Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Colorectal Cancer Research Center Shanghai 200092China

The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post *** retaining cells(LRCs)expressing SRY-box transcription factor 9(SOX9)promote epithelial repair by replenishing LGR5 t intestinal stem cells(ISCs).While,LRCs are also considered precursor cells for enteroendocrine cells(EECs)which exacerbate mucosal damage in inflammatory bowel disease(IBD).The factors that determine LRC-EEC differentiation and the effect of intervening in LRC-EEC differentiation on IBD remain *** this study,we investigated the effects of a natural anthraquinone called aloe emodin(derived from the Chinese herb rhubarb)on mucosal healing in IBD *** findings demonstrated that aloe emodin effectively interfered with the differentiation to EECs and preserved a higher number of SOX9t LRCs,thereby promoting mucosal ***,we discovered that aloe emodin acted as an antagonist of free fatty acid receptors(FFAR1),suppressing the FFAR1-mediated Gbg/serine/threonine-protein kinase(AKT)pathway and promoting the translocation of forkhead box protein O1(FOXO1)into the nucleus,ultimately resulting in the intervention of differentiation *** findings reveal the effect of free fatty acid accessibility on EEC differentiation and introduce a strategy for promoting mucosal healing in IBD by regulating the FFAR1/AKT/FOXO1 signaling pathway.

关键词： LRCs ISCs EECs IBD SOX9 Aloe emodin FFAR1 FOXO1

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