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Nano research 2024年第5期17卷 3455-3461页

作者： Meichun Qin Chaolong Liu Shouhen Xu Jianguo Tang Institute of Hybrid Materials National Center of International Joint Research for Hybrid Materials TechnologyNational Base of International Sci.and Tech.Cooperation on Hybrid MaterialsCollege of Materials Science and EngineeringQingdao UniversityQingdao266071China Department of pharmaceutics School of PharmacyQingdao UniversityQingdao266071China

Electrocatalytic n-valeraldehyde oxidation reaction was an inexpensive and eco-friendly method to control n-valeraldehyde contamination and produce high value-added ***,low-cost and readily available electrocatalysts with high current efficiency were urgently ***,two-dimensional porous carbon derived from pollen with enlarged interlayer distance was built by alkali activation method,applying in electrocatalytic n-valeraldehyde oxidation *** enlarged interlayer distance was verified by X-ray diffraction(XRD)and high-angle annular dark-field scanning transmission electron microscope(HAADF-STEM).Electrocatalytic experiments consequences showed activated biomass derived carbon possessed a higher electrocatalytic activity and octane selectivity than unactivated *** tests and in situ infrared experiments demonstrated that enlarged interlayer distance was positively correlated with specific surface area of catalysts,large specific surface area provided abundant absorption sites,facilitated the adsorption for n-valeraldehyde,and further promoted the transformation of n-valeraldehyde to *** work also provides a new avenue for creating high-performance electrocatalysts in terms of lattice engineering.

关键词： biomass derived carbon lattice expansion high specific surface area upgrade of n-valeraldehyde

Genome-wide CRISPR screens identify CLC-2 as a drug target for anti-herpesvirus therapy: tackling herpesvirus drug resistance

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Science China Life Sciences 2024年

作者： Fayu Yang Nan Wei Shuo Cai Jing Liu Qingping Lan Hao Zhang Lu Shang Bo Zheng Mi Wang Yingchun Liu Lifang Zhang Chenzhong Fei Wu Tong Changlong Liu Ersheng Kuang Guangzhi Tong Feng Gu Shanghai Veterinary research Institute Chinese Academy of Agricultural Sciences Key laboratory of Veterinary Chemical Drugs and pharmaceutics Ministry of Agriculture and Rural Affairs State Key laboratory for Animal Disease Control and Prevention College of Veterinary Medicine Lanzhou University Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences Institute of Human Virology Zhongshan School of Medicine Sun Yat-Sen University School of Medicine Tsinghua University

The emergence of drug resistance to virus(i.e., acyclovir(ACV) to herpesviruses) has been termed one of the common clinical issues,emphasizing the discovery of new antiviral agents. To address it, a genome-wide clustered regularly interspaced short palindromic repeats(CRISPR) screening was performed in mouse haploid embryonic stem cells infected with pseudorabies virus(PRV), an α-herpesvirus causing human and pig diseases. The results demonstrated that type 2 voltage-gated chloride channels(CLC-2) encoded by one of the identified genes, CLCN2, is a potential drug target for anti-herpesvirus therapy. CLC-2 inhibitors, omeprazole(OME) and 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid(DIDS), can efficiently inhibit infection of multiple herpesviruses in cellulo(i.e., PRV, HSV and EBV), and effectively treat murine herpes simplex encephalitis(HSE). Additionally, DIDS was found to inhibit HSV-1 replication by blocking the PI3K/Akt *** importantly, both DIDS and OME were able to inhibit ACV-resistant HSV-1 strain infection. The study's findings suggest that targeting host-cell factors such as CLC-2 may be a promising approach to tackling herpesvirus drug resistance. The discovery of CLC-2 as a potential drug target for anti-herpesvirus therapy provides a new direction for the development of novel antiviral agents.

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Advantages of nanocarriers for basic research in the field of traumatic brain injury

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Neural Regeneration research 2024年第2期19卷 237-245页

作者： Xingshuang Song Yizhi Zhang Ziyan Tang Lina Du School of Pharmaceutical Sciences Shandong University of Traditional Chinese MedicineJinanShandong ProvinceChina Department of pharmaceutics Beijing Institute of Radiation MedicineBeijingChina

A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain *** overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery *** this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain *** also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and *** can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug ***,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.

关键词： blood-brain barriers brain targeting central nervous system extracellular vesicles inflammatory factor microglial cell nanocarriers nanoparticles neural restoration traumatic brain injury

Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1525-1541页

作者： Qi Shang Wandong Liu Faith Leslie Jiapei Yang Mingmei Guo Mingjiao Sun Guangji Zhang Qiang Zhang Feihu Wang School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Basic Medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province Hangzhou 310053China Department of Chemical and Biomolecular Engineering Whiting School of Engineeringthe Johns Hopkins UniversityBaltimoreMD 21218USA Traditional Chinese Medicine“Preventing Disease”Wisdom Health Project research Center of Zhejiang Hangzhou 310053China Beijing Key laboratory of Molecular pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

关键词： Chinese herbal medicines Nano-formulation Activeingredients Drug delivery Cancer immunotherapy Innate immune system Adaptive immune system

Core and variable antimicrobial resistance genes in the gut microbiomes of Chinese and European pigs

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Zoological research 2024年第1期45卷 189-200页

作者： Cui-Hong Tong Zhi-Peng Huo Lu Diao Dan-Yu Xiao Ruo-Nan Zhao Zhen-Ling Zeng Wen-Guang Xiong Guangdong Provincial Key laboratory of Veterinary pharmaceutics Development and Safety Evaluation South China Agricultural UniversityGuangzhouGuangdong 510642China National Risk Assessment laboratory for Antimicrobial Resistance of Animal Original Bacteria College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouGuangdong 510642China National laboratory of Safety Evaluation(Environmental Assessment)of Veterinary Drugs South China Agricultural UniversityGuangzhouGuangdong 510642China National Reference laboratory of Veterinary Drug Residues South China Agricultural UniversityGuangzhouGuangdong 510642China

Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial *** its importance,the characterization of ARGs and microbiome structures,as well as the identification of indicators for routine ARG monitoring in pig farms,are still lacking,particularly concerning variations in antimicrobial exposure in different countries or ***,metagenomics and random forest machine learning were used to elucidate the ARG profiles,microbiome structures,and ARG contamination indicators in pig manure under different antimicrobial pressures between China and *** showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs(P<0.05).ANT(6)-Ib,APH(3')-IIIa,and tet(40)were identified as shared core ARGs between the two pig ***,the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical *** and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs,*** ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100%and 98.7%,*** for assessing ARG contamination in Chinese and European pigs also achieved high accuracy(r=0.72-0.88).Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 *** results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.

关键词： Metagenomic Pig manure Antimicrobial pressure Antimicrobial resistance genes Microbiome

research advances of nanoparticles for CAR-T therapy in solid tumors

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Chinese Chemical Letters 2024年第9期35卷 72-82页

作者： Bohan Chen Liming Gong Jing Feng Mingji Jin Liqing Chen Zhonggao Gao Wei Huang State Key laboratory of Bioactive Substance and Function of Natural Medicines Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing Key laboratory of Drug Delivery Technology and Novel Formulations Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China School of Pharmacy Qingdao UniversityQingdao 266071China

As one of the most promising adoptive T-cell therapies,chimeric antigen receptor T-cell(CAR-T)therapy has acquired Food and Drug Administration(FDA)approval for a variety of products and has been used successfully in the treatment of malignant hematological ***-T therapy,on the other hand,faces a number of obstacles in the field of solid tumor therapy that limit its widespread clinical *** advances in nanoparticle research in cancer therapy and immunotherapy have been made in recent years,providing novel strategies to address the challenges encountered by CAR-T therapy in the treatment of solid *** review commences with a comprehensive explanation of the basic framework of CAR-T therapy as well as the challenges it faces in the treatment of solid ***,we encapsulate a summary of the developmental research combining nanoparticles with CAR-T cells for the treatment of solid tumors,which includes gene transfection,cell activation and expansion,targeted infiltration,immune escape inhibition,and combination with other *** with the overview of the research progress,a discussion has been initiated on the challenges and perspectives of CAR-T based on nanoparticles.

关键词： CAR-T therapy Nanoparticles Solid tumors Immunotherapy T cell

Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

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Chinese Chemical Letters 2024年第2期35卷 323-328页

作者： Qiu Wang Qikun Jiang Dan Li Zimeng Yang Lin Gao Fan Liu Chang Li Yao Feng Zhonggui He Cong Luo Jin Sun Department of pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Kangya of Ningxia Pharmaceutical Co.Ltd. Yinchuan 750000China

Small interfering RNA(siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory ***,the effective delivery of siRNA to desired destination still remains challenging due to poor stability,high molecular weight and negative ***,ionizable lipid nanoparticle(LNP)has been extensively used as vector for effective delivery of ***,we report a mannose-modified LNP(M-MC_(3) LNP@TNFα)loading tumor necrosis factorα(TNFα)siRNA for targeting liver macrophages,achieving effectively inhibit acute liver *** M-MC_(3) LNP@TNFαnot only increases the internalization of LNP by macrophages,but also enhances the gene silencing efficiency of TNFαin ***,the M-MC_(3) LNP@TNFαexhibits higher accumulation in liver of healthy mice than that of MC_(3) LNP@TNFα(un-modified LNP)owing to the targeting effect of *** expected,the M-MC_(3) LNP@TNFαsignificantly suppresses the expression of TNFαand ameliorates liver damage in acute liver injury *** a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

关键词： Lipid nanoparticle Targeting siRNA delivery Acute liver injury Gene silencing Tumor necrosis factorα

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis

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Current Medical Science 2024年第4期44卷 809-819页

作者： Chen-guang YAO Zi-jia ZHAO Ting TAN Jiang-ning YAN Zhong-wei CHEN Jun-tao XIONG Han-luo LI Yan-hong WEI Kang-hong HU Sino-German Biomedical Center Hubei Provincial Key Laboratory of Industrial MicrobiologyCooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province)Key Laboratory of Fermentation Engineering(Ministry of Education)National“111”Center for Cellular Regulation and Molecular PharmaceuticsHubei University of TechnologyWuhan430068China Center for Evaluation of Hubei Medical Products Administration Wuhan430068China

Objective Lindqvist-type polyoxometalates(POMs)exhibit potential antitumor *** study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying *** Using different cancer cell lines,the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side *** colony formation assay,autophagy detection,mitochondrial observation,qRT-PCR,Western blotting,and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related *** MO-4,a Lindqvist-type POM linking a proline at its side strain,was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer *** was found that MO-4 induced the apoptosis of multiple types of breast cancer ***,MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species(ROS)levels and resulting in *** vivo,breast tumor growth and distant metastasis were significantly reduced following MO-4 *** Collectively,the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

关键词： antitumor breast cancer polyoxometalate mitochondria mitophagy

Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membranedecorated nanoparticles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3218-3231页

作者： Wen Zhang Yihui Zhai Ying Cai Xiang Gong Yunxuan Jiang Rong Rong Chao Zheng Binyu Zhu Helen He Zhu Hao Wang Yaping Li Pengcheng Zhang China State Institute of Pharmaceutical Industry Shanghai 201203China State Key laboratory of Drug research&Center of pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Biomedical Engineering&State Key laboratory of Advanced Medical Materials and Devices ShanghaiTech UniversityShanghai 201210China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Yantai Institute of Materia Medica Shandong 264000China State Key laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127China University of Chinese Academy of Sciences Beijing 100049China

Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocompatibility complex I(MHC-I)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-I-deficient *** on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer *** released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 *** also block CD47-mediated phagocytosis *** inhibit the growth of MHC-I-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important *** macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophagemediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

关键词： MHC-I deficiency Macrophage CD47 Immunotherapy Triple-negative breast cancer Phagocytosis Immune checkpoint Innate immunity

The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

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Oncology research 2024年第7期32卷 1231-1237页

作者： MOHAMMAD-TAGHI MORADI DHIYA ALTEMEMY MAJID ASADI-SAMANI PEGAH KHOSRAVIAN MARZIYEH SOLTANI LEILA HASHEMI AZADEH SAMIEI-SEFAT Medical Plants research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran Department of pharmaceutics College of PharmacyAl-Zahraa University for WomenKarbalaIraq Cellular and Molecular research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran

Background:Despite the availability of chemotherapy drugs such as 5-ﬂuorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side *** study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their *** proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)*** synergistic effect of 5-FU and celastrol was studied using Compusyn *** DNA content at different phases of the cell cycle and apoptosis rate was measured usingﬂow ***:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU signiﬁcantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,*** mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,*** addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis ***:Although celastrol could decrease the concentration of 5-ﬂuorouracil that sufﬁced to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

关键词： Gastric cancer Celastrol Terpenoid Cell cycle regulation Apoptosis Synergism