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ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 341-353页

作者： Zhibin YAN Ying SHI Runling YANG jijun XUE Caiyun fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhou310018China State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou University Lanzhou 730000China Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical Sciences2019RU066Lanzhou UniversityLanzhou 730000China

Kidney fibrosis is an inevitable result of various chronic kidney diseases(CKDs)and significantly contributes to end-stage renal failure.Currently,there is no specific treatment available for renal fibrosis.ELA13(amino acid sequence:RRCMPLHSRVPFP)is a conserved region of ELABELA in all vertebrates;however,its biological activity has been very little studied.In the present study,we evaluated the therapeutic effect of ELA13 on transforming growth factor-β1(TGF-β1)-treated NRK-52E cells and unilateral ureteral occlusion(UUO)mice.Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum,and reduce the expression of fibrosis biomarkers confirmed by Masson staining,immunohistochemistry,real-time polymerase chain reaction(RT-PCR),and western blot.Inflammation biomarkers were increased after UUO and decreased by administration of ELA13.furthermore,we found that the levels of essential molecules in the mothers against decapentaplegic(Smad)and extracellular signal-regulated kinase(ERK)pathways were reduced by ELA13 treatment in vivo and in vitro.In conclusion,ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

关键词： ELA13 Kidney fibrosis Inflammation Smad Extracllular signal-regulated kinase(ERK)

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Graph attention network for global search of atomic clusters:A case study of Ag_(n)(n=14-26)clusters

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Frontiers of physics 2023年第1期18卷 105-113页

作者： Linwei Sai Li fu Qiuying Du jijun Zhao School of Science Hohai UniversityChangzhou 213022China Key Laboratory of Materials Modification by Laser Ion and Electron Beams(Dalian University of Technology)Ministry of EducationDalian 116024China College of Physics and Electronic Information Inner Mongolia Normal UniversityHohhot 010022China

Due to coexistence of huge number of structural isomers,global search for the ground-state structures of atomic clusters is a challenging issue.The difficulty also originates from the computational cost of ab initio methods for describing the potential energy surface.Recently,machine learning techniques have been widely utilized to accelerate materials discovery and molecular simulation.Compared to the commonly used artificial neural network,graph network is naturally suitable for clusters with flexible geometric environment of each atom.Herein we develop a cluster graph attention network(CGANet)by aggregating information of neighboring vertices and edges using attention mechanism,which can precisely predict the binding energy and force of silver clusters with root mean square error of 5.4 meV/atom and mean absolute error of 42.3 meV/Å,respectively.As a proof-of-concept,we have performed global optimization of mediumsized Agn clusters(n=14–26)by combining CGANet and genetic algorithm.The reported ground-state structures for n=14–21,have been successfully reproduced,while entirely new lowest-energy structures are obtained for n=22–26.In addition to the description of potential energy surface,the CGANet is also applied to predict the electronic properties of clusters,such as HOMO energy and HOMO-LUMO gap.With accuracy comparable to ab initio methods and acceleration by at least two orders of magnitude,CGANet holds great promise in global search of lowest-energy structures of large clusters and inverse design of functional clusters.

关键词： deep learning graph attention network potential surface fitting Ag clusters global search

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Prussian blue nanosphere-embedded in situ hydrogel for photothermal therapy by peritumoral administration

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Acta Pharmaceutica Sinica B 2019年第3期9卷 604-614页

作者： Jijun Fu Bo Wu Minyan Wei Yugang Huang Yi Zhou Qiang Zhang Lingran Du The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou Medical UniversityGuangzhou510700China Key Laboratory of Molecular Target&Clinical Pharmacology School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou511436China Center of Pharmaceutical Research and Development School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou511436China

To establish an injectable hydrogel containing Prussian blue(PB) nanospheres for photothermal therapy against cancer, PB nanospheres were prepared by one-pot synthesis and the thermosensitive Pluronic F127 was used as the hydrogel matrix. The PB nanospheres and the hydrogel were characterized by shape, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation, as well as the rheological features. The effect of the PB nanospheres and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention,photothermal efficacy, therapeutic effects and systemic toxicity of the hydrogel were assessed in a tumor-bearing mouse model. The PB nanospheres had a diameter of about 150 nm and exhibited satisfactory serum stability, photo-heat convert ability and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanospherecontaining hydrogel showed a phase transition at body temperature and, as a result, a long retention time in vivo. The photothermal agent-embedded hydrogel displayed promising photothermal therapeutic effects in the tumor-bearing mouse model with little-to-no systemic toxicity after peritumoral administration.

关键词： Prussian blue Nanospheres Hydrogel Thermosensitive Injectable In situ Photothermal

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Dual-targeting nanovesicles enhance specificity to dynamic tumor cells in vitro and in vivo via manipulation of αvβ3-ligand binding

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2183-2197页

作者： Yang Song Xiangfu Guo Jijun Fu Bing He Xueqing Wang Wenbing Dai Hua Zhang Qiang Zhang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Guangzhou Medical University School of Pharmaceutical SciencesGuangzhou 511436China

The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors,and the related targeting nanomedicines are rarely reported.The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor.Namely,the binding feature is very essential in this case.Herein,we utilized HSPC,PEG-DSPE,cholesterol and two avb3 ligands(RGDm7 and DT4)with different binding rates to build dual-targeting nanovesicles,in an effort to achieve a"fast-binding/slow-unbinding"function.It was demonstrated that the dual-targeting nanovesicles actualized effi-cient cellular uptake and antitumor effect in vitro both for static and dynamic tumor cells.Besides,the potency of the dual-targeting vesicles for flowing tumor cells was better than that for static tumor cells.Then,a tumor metastasis mice model and a leukemia mice model were established to detect the killing ability of the drug-loaded dual-targeting vesicles to dynamic tumor cells in vivo.The therapy efficacy of the dual-targeting system was higher than other controls including single-targeting ones.Generally,it seems possible to strengthen drug-targeting to dynamic tumor cells via the control of ligandereceptor interaction.

关键词： Dual-targeting Lipid vesicle Flowing condition Leukemia Circulating tumor cells Fluidic shear stress

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Computed tomography and photoacoustic imaging guided photodynamic therapy against breast cancer based on mesoporous platinum with insitu oxygen generation ability

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1719-1729页

作者： Lingyan Zhang Mifang Li Quan Zhou Meng Dang Yuxia Tang Shouju Wang Jijun Fu Zhaogang Teng Guangming Lu Department of Medical Imaging Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjing 210002China Department of Medical Imaging The Third Affiliated HospitalSouthern Medical UniversityGuangzhou 510630China Key Laboratory for Organic Electronics&Information Displays and Institute of Advanced Materials Jiangsu Key Laboratory for BiosensorsJiangsu National Synergetic Innovation Centre for Advanced MaterialsNanjing University of Posts and TelecommunicationsNanjing 210046China Departm ent of Medical Imaging Jiangsu Province HospitalNanjing 210029China Key Laboratory of Molecular Target&Clinical Pharmacology School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China

Photodynamic therapy(PDT)has been widely used in cancer treatment.However,hypoxia in most solid tumors seriously restricts the efficacy of PDT.To improve the hypoxic microenvironment,we designed a novel mesoporous platinum(mPt)nanoplatform to catalyze hydrogen peroxide(H2 O2)within the tumor cells in situ without an extra enzyme.During the fabrication,the carboxy terminus of the photosensitizer chlorin e6(Ce6)was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol(SH-PEG-NH2)by a condensation reaction,and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH2.Material,cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2 O2 to produce oxygen(O2)and that Ce6 transformed O2 to generate reactive oxygen species(ROS)upon laser irradiation.The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation.Due to the high atomic number and good near-infrared absorption for Pt,this Pt@PEG-Ce6 nanoplatform showed computed tomography(CT)and photoacoustic(PA)dual-mode imaging ability,thus providing an important tool for monitoring the tumor hypoxic microenvironment.Moreover,the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-la(HIF-1α)and programmed death-1(PD-1)in tumors,discussing the relationship between hypoxia,PD-1,and PDT for the first time.

关键词： Mesoporous platinum Photodynamic therapy Tumor hypoxia Photoacoustic imaging Computed tomography imaging

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MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1

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Acta Pharmaceutica Sinica B 2020年第6期10卷 1036-1046页

作者： Lu Liang Jijun Fu Siran Wang Huiyu Cen Lingmin Zhang Safur Rehman Mandukhail Lingran Du Qianni Wu Peiquan Zhang Xiyong Yu Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences&the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China Department of Prosthodontics the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150001China

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer.However,the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown.Here,we found that miR-142-3p was significantly downregulated in the doxorubicin(DOX)-resistant MCF-7 cell line(MCF-7/DOX).MiR-142-3p overexpression increased DOX sensitivity and enhanced DOXinduced apoptosis in breast cancer cells.High-mobility group box 1(HMGB1)is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression.Moreover,overexpres sion of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation.In conclusion,miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB 1.The miR-142-3 p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.

关键词： Breast cancer MCF-7 cell line HMGB1 MiR-142-3p Drug resistance Chemosensitivity

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One-pot preparation of nanodispersion with readily available components for localized tumor photothermal and photodynamic therapy

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Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 120-128页

作者： Anpu Yang Yanan Sun Bochen Lyu Binlong Chen Zhipu Fan Minghui Li Yao Zhao Jijun Fu Bing He Hua Zhang Xueqing Wang Wenbing Dai Qiang Zhang State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciencesxueyuan road 38haidian districtPeking UniversityBeijing 100191China Beijing Key Laboratory of Molecular Pharmaceutics School of Pharmaceutical SciencesPeking UniversityBeijing 100191China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns(SWCNH), zinc phthalocyanine(ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 ℃ due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise(to 65 ℃) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.

关键词： Photodynamic therapy Photothermal therapy Carbon nanohorn Zinc phthalocyanine

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Dietary ferulic acid and vanillic acid on inflammation,gut barrier function and growth performance in lipopolysaccharide-challenged piglets

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Animal Nutrition 2022年第1期8卷 144-152页

作者： Ruizhi Hu Shusong Wu Baizhen Li jijun Tan Jiahao Yan Ying Wang Zhiyi Tang Ming Liu Chenxing fu Hongfu Zhang Jianhua He Hunan Collaborative Innovation Center for Utilization of Botanical functional Ingredients College of Animal Science and TechnologyHunan Agricultural UniversityChangsha410128China Beijing China-Agri HongKe Bio-Technology Co. Ltd.Beijing102206China State Key Laboratory of Animal Nutrition Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijing100193China

Ferulic acid(FA)and vanillic acid(VA)are considered as major phenolic metabolites of cyanidin 3-glucoside,a polyphenol that widely exists in plants that possess a protective effect against oxidative stress and inflammation in our previous study.This study aimed to investigate the effect of FA and VA on inflammation,gut barrier function,and growth performance in a weaned piglet model challenged with lipopolysaccharide(LPS).Thirty-six piglets(PIC 337×C48,28 d of age)were randomly allocated into 3 treatments with 6 replicate pens(2 piglets per pen).They were fed with a basal diet or a diet containing 4,000 mg/kg of FA or VA.Dietary supplementation of VA significantly increased average daily gain(ADG)(P<0.05).Both FA and VA decreased serum levels of thiobarbituric acid reactive substances(TBARS),interlukin(IL)-1β,IL-2,IL-6,and tumor necrosis factor(TNF)-α(P<0.05),and enhanced the expression of tight junction protein oclaudin(P<0.05).Analysis of gut microbiota indicated that both FA and VA increased the Firmicutes/Bacteroidetes ratio alongside reducing the relative abundance of the Prevotellaceae family including Prevotella 9 and Prevotella 2 genera,but enriched the Lachoiraceaea family including the Lachnospiraceae FCS020 group(P<0.05).Moreover,VA reduced the relative abundance of Prevotella 7 and Prevotella 1 but enriched Lachnospira,Eubacterium eligens group,and Eubacterium xylanophilum group(P<0.05),while FA showed a limited effect on these genera.The results demonstrated that both VA and FA could alleviate inflammation and oxidative stress,but only VA has a significant positive effect on the growth performance of LPS-challenged piglets potentially through modulating gut microbiota.

关键词： Ferulic acid Vanillic acid Inflammation Gut barrier function Growth performance Piglet

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A magnetism/laser-auxiliary cascaded drug delivery to pulmonary carcinoma

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1549-1562页

作者： Jialiang Lin Qingqing Yin Binlong Chen Haoran Zhang Dong Mei Jijun Fu Bing He Hua Zhang Wenbing Dai Xueqing Wang Yiguang Wang Qiang Zhang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers.The ultrasmall superparamagnetic iron oxide nanoparticles(USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin(Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed in vivo that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.

关键词： auxiliary overcome delivery

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“一带一路”贸易网络结构及其对区域经济联动的影响

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南京社会科学 2022年第11期 42-50页

作者：杨继军傅军南京财经大学国际经贸学院南京210023 南京财经大学现代服务业智库南京210023

基于“一带一路”沿线国家2000—2019年贸易数据,利用社会网络分析法,廓清了沿线国家的贸易网络拓扑结构,发现“一带一路”贸易网络的整体密度增加,但呈现出非均质特征,中国、印度、新加坡等国家处于网络的核心节点位置,对网络的整体功... 详细信息

基于“一带一路”沿线国家2000—2019年贸易数据,利用社会网络分析法,廓清了沿线国家的贸易网络拓扑结构,发现“一带一路”贸易网络的整体密度增加,但呈现出非均质特征,中国、印度、新加坡等国家处于网络的核心节点位置,对网络的整体功能起着决定性作用。计量分析表明,“一带一路”贸易网络结构对区域经济联动具有显著影响,网络中心度高的国家,与他国的贸易往来更密切,经济联动程度也更高;凝聚子群分析揭示,经济联动具有分层聚类的特征,同一子群内的国家间经济联动水平更高。为此,应加强“一带一路”基础设施建设,提高区域内的贸易通达性水平;推进“一带一路”倡议,充分发挥沿线贸易网络核心国家的关键作用,以形成对区域内边缘国家的辐射带动作用,构建合作共赢、联动发展的区域经济生态。

关键词： “一带一路” 贸易网络凝聚子群经济联动

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