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Inhalable nanoparticles with enhanced cuproptosis and cGAS-STING activation for synergistic lung metastasis immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3697-3710页

作者： Chongzheng Yan Huaiyou Lv Yafei Feng Yuhan Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key University Laboratory of Pharmaceutics&Drug Delivery Systems of Shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Department of Pharmacy Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityYantai 264001China

Due to the insufficient Cu^(+)accumulation,Cu^(+)efflux mechanism,and highly immunosuppressive tumor microenvironment(TME)in lung metastasis,the cuproptosis efficacy is ***,an inhalable nanodevice(CLDCu)is constructed to successfully overcome the drawbacks of *** consists of a Cu^(2+)-chitosan shell and low molecular weight heparin-tocopherol succinate(LMWH-TOS,LT)core with disulfiram(DSF)*** prepared CLDCu can be inhaled and accumulate in large amounts in lung lesions(63.6%)with 56.5 times higher than intravenous *** tumor cells,the mild acidity triggers the co-release of DSF and Cu2+,thus generating bis(diethyldithiocarbamate)-copper(CuET)to block Cu^(+)efflux protein ATP7B and forming toxic Cu^(+),leading to enhanced ***,the released chitosan cooperates with CLDCu-induced cuproptosis to activate stimulator of interferon genes(STING)pathway,which significantly potentiates dendritic cells(DCs)maturation,as wells as evokes innate and adaptive *** lung metastatic mice model,CLDCu is found to induce cuproptosis and reverse the immunosuppressive TME by inhalation ***,CLDCu combined with anti-programmed cell death protein ligand-1 antibody(aPD-L1)provokes stronger antitumor ***,nanomedicine that combines cuproptosis with STING activation is a novel strategy for tumor immunotherapy.

关键词： Cuproptosis cGAS-STING activation Disulfiram Inhalation administration Tumor microenvironment PD-L1 checkpoint blockade Lung metastasis Immunotherapy

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The in vitro digestion fates of diacylglycerol under different intestinal conditions:a potential lipid source for lipid indigestion patients

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food Science and Human Wellness 2024年第2期13卷 1079-1092页

作者： Qingqing Xu Weifei Wang Dongxiao Sun-Waterhouse Qian Zou Menglei Yan Xuan Liu Dongming Lan Yonghua Wang school of food Science and Engineering South China University of TechnologyGuangzhou 510640China Sericultural and Agri-food Research Institute Guangdong Academy of Agricultural SciencesGuangzhou 510610China school of Chemical sciences The University of AucklandPrivate Bag 92019New Zealand Guangdong Youmei Institute of Intelligent Bio-manufacturing Co. Ltd.Foshan 528200China

The in vitro digestion models mimicking the gastrointestinal(GI)tract of general population and lipid indigestion patients(with lower levels of bile salts or pancreatic lipase)were selected to investigate whether diacylglycerols(DAGs)are potential good lipid sources for these *** oil-based DAG(LD)and linseed oil(LT)were ***-based emulsion((83.74±1.23)%)had higher lipolysis degree than LT-based emulsion((74.47±1.16)%)when monitoring the GI tract of normal population as previously *** conditions seriously decreased the digestive degree of LT-based emulsion((40.23±2.48)%-(66.50±3.70)%)while showed less influence on LD-based emulsion((64.18±2.41)%-(81.85±3.45)%).As opposed to LT-based emulsion,LD-based emulsion exhibited preference for releasing unsaturated fatty acids(especially oleic acid andα-linolenic acid)due to their different glycerolipid ***-based emulsion showed potential for providing lipids and nutrients(including essential fatty acids)for lipid indigestion patients.

关键词： Diacylglycerol In vitro digestion Lipolysis level Cholestatic Exocrine pancreatic insufficiency

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Insights into Euphorbia diversity: Probing the contrasts between Euphorbia fischeriana Steud and Euphorbia ebracteolata Hayata

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Journal of pharmaceutical Analysis 2024年第5期14卷 775-779页

作者： Kaicheng Du Yi Zhang Lei Sun Muke Tao Tiantian Zuo Yumeng Wang Zhengfeng Zhang Dali Meng school of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang110016China NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances Chongqing Institute for Food and Drug ControlChongqing401121China National Institutes for food and Drug Control Beijing100050China

In traditional Chinese medicine(TCM),Euphorbia fischeriana Steud(***)and Euphorbia ebracteolata Hayata(***),commonly referred to as“Langdu”,are widely extensively utilized for treating lymphatic tuberculosis and ringworm[1].Both plant species are perennial herbaceous plants mainly distributed in northeastern China,Mongolia,Russia(Siberia),and Republic of Korea[2].There have been many reports on the chemical constituents and pharmacological effects of the two plant species,which has made more and more researchers realize that there may be differences between *** and *** some cases,long-term improper use of herbal medicines can even lead to life-threatening conditions[3,4].Therefore,it is essential to employ an effective technology to differentiate between these two plants based on their chemical constituents and biological activities,so as to reduce the harm caused by the mixing and misuse of medicinal ***,the present paper describes a study of the differences between *** and ***,using untargeted plant metabolomics and biological activity *** study aims to provide valuable insight into their equivalence and potential interchangeability in TCM and clinical medication.

关键词： Euphorbia Siberia northeastern

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RACK1A promotes hypocotyl elongation by scaffolding light signaling components in Arabidopsis

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Journal of Integrative Plant Biology 2024年第5期66卷 956-972页

作者： Yajuan Fu Wei Zhu Yeling Zhou Yujing Su Zhiyong Li Dayan Zhang Dong Zhang Jinyu Shen Jiansheng Liang Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes Department of BiologySchool of Life SciencesInstitute of Plant and Food SciencesSouthern University of Science and TechnologyShenzhen 518055China

Plants deploy versatile scaffold proteins to intricately modulate complex cell *** these,RACK1A(Receptors for Activated C Kinase 1A)stands out as a multifaceted scaffold protein functioning as a central integrative hub for diverse signaling ***,the precise mechanisms by which RACK1A orchestrates signal transduction to optimize seedling development remain largely ***,we demonstrate that RACK1A facilitates hypocotyl elongation by functioning as a flexible platform that connects multiple key components of light signaling ***1A interacts with PHYTOCHROME INTERACTING FACTOR(PIF)3,enhances PIF3 binding to the promoter of BBX11 and down-regulates its ***,RACK1A associates with ELONGATED HYPOCOTYL 5(HY5)to repress HY5 biochemical activity toward target genes,ultimately contributing to hypocotyl *** darkness,RACK1A is targeted by CONSTITUTIVELY PHOTOMORPHOGENIC(COP)1 upon phosphorylation and subjected to COP1-mediated degradation via the 26 S proteasome *** findings provide new insights into how plants utilize scaffold proteins to regulate hypocotyl elongation,ensuring proper skoto-and photo-morphogenic development.

关键词： Arabidopsis hypocotyl development light signaling components RACK1 scaffoldprotein

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Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

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Oncology Research 2024年第2期32卷 309-323页

作者： BEHROOZ JOHARI MILAD PARVINZAD LEILAN MAHMOUD GHARBAVI YOUSEF MORTAZAVI ALI SHARAFI HAMED REZAEEJAM Department of Medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Zanjan pharmaceutical Biotechnology Research Center Zanjan University of Medical SciencesZanjanIran Nanotechnology Research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell *** and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 *** nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical ***,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer *** anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized *** revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation *** can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

关键词： Combinational therapy Antisense therapy Myc signaling pathway Niosomes Radiation therapy SeNPs

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Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease

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Journal of pharmaceutical Analysis 2024年第4期14卷 552-561页

作者： Panpan Chen Zihan Zhu Haoyuan Geng Xiaoqing Cui Yuhao Han Lei Wang Yaqi Zhang Heng Lu Xiao Wang Yun Zhang Chenglong Sun Key Laboratory for Natural Active pharmaceutical Constituents Research in Universities of Shandong Province School of Pharmaceutical SciencesQilu University of Technology(Shandong Academy of Sciences)Jinan250014China Key Laboratory for Applied Technology of Sophisticated Analytical Instruments of Shandong Province Shandong Analysis and Test CenterQilu University of Technology(Shandong Academy of Sciences)Jinan250014China school of Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China Biology Institute Qilu University of Technology(Shandong Academy of Sciences)Jinan250103China

Eclipta prostrata *** been used in traditional medicine and known for its liver-protective properties for ***(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in *** ***,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be *** a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics *** results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the *** biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also *** on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of *** study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a“multi-omics”platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

关键词： Spatial metabolomics Transcriptomics Non-alcoholic fatty liver disease Wedelolactone Demethylwedelolactone

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An efficient approach for the treatment of radioactive waste perfluoropolyether lubricants via a synergistic effect of thermal catalysis and immobilization

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Journal of Environmental sciences 2024年第2期136卷 512-522页

作者： Xinhang Du Wenhua Tong Xinyu Zhou Jia Luo Yuqiu Liu Yabo Wang Panyu Li Yongkui Zhang Department of pharmaceutical&Biological Engineering School of Chemical EngineeringSichuan UniversityChengdu 610065China

Perfluoropolyether(PFPE)lubricants are a kind of high-molecular polymer with many excellent ***,the use of PFPEs in the nuclear industry can lead to partial decomposition and carrying radionuclides,resulting in a large amount of radioactive waste PFPE lubricants ***,radioactive waste PFPE lubricants are difficult to be effectively treated due to their high stability,the risk of possible leakage of radionuclides,and hypertoxic fluorine-containing *** this study,without any precedent,a strategy of Mn O_(2)-catalyzed decomposition and Na_(2)CO_(3)-immobilized conversion was proposed for PFPE lubricant decomposition and fluorine immobilization simultaneously based on the Lewis acid-base and oxygen vacancies concept.A high fluorine conversion efficiency of 95.4%was ***,the mechanism of decomposition suggested that Mn O_(2)mainly provided Lewis acid sites and attacked the(basic)fluorine or oxygen atoms in PFPE *** decomposition of PFPE chains was proceed down and volatile fluorine-containing gas was released by partial electron transfer,intramolecular disproportionation reaction,and unzipping ***,gas by-products could be further oxidized and then immobilized into fluoride salts by carbonate solid ***,this study provides a simple,safe,and potentially practical strategy for the harmless conversion of refractory fluorinated organic wastes,especially perfluoropolymers.

关键词： Perfluoropolyether lubricants Catalyzed decomposition Fluorine-containing gas Immobilized conversion Fluoride

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Feedback enhanced tumor targeting delivery of albumin-based nanomedicine to amplify photodynamic therapy by regulating AMPK signaling and inhibiting GSTs

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Chinese Chemical Letters 2024年第8期35卷 481-485页

作者： Jiaqi Huang Renjiang Kong Yanmei Li Ni Yan Yeyang Wu Ziwen Qiu Zhenming Lu Xiaona Rao Shiying Li Hong Cheng school of Biomedical Engineering&Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering Southern Medical UniversityGuangzhou 510515China school of pharmaceutical sciences Guangzhou Medical UniversityGuangzhou 511436China

Oxidative therapies receive a limited antitumor efficiency due to the insufficient reactive oxygen species(ROS)levels at focal sites and the evolvement of antioxidant defense ***,we develop an albumin-based nanomedicine to co-deliver chlorin e6(Ce6)and COH-SR4(CS),which can simultaneously enhance the yield and lethality of intracellular ROS for amplified photodynamic therapy(PDT).In which,CS acts as both an activator of AMP-activated protein kinase(AMPK)and an inhibitor of glutathione S-transferases(GSTs).Benefiting from it,the prepared HSA-Ce6@COH-SR4(HCCS)enables positive feed-back uptake by promoting AMPK phosphorylation,leading to rapid and extensive tumor accumulation of *** a result,HCCS obviously increases the ROS production to elevate intracellular oxidative ***,HCCS can inhibit GSTs to disturb the antioxidant defense system of tumor cells,intensifying the oxidative damage of ***,the PDT of HCCS is significantly strengthened by improving the ROS yield and lethality,which greatly declines the proliferation of breast cancer in *** study may open a window in the development of drug co-delivery system for enhanced oxidative therapy of tumors.

关键词： Human serum albumin Drug delivery Reactive oxygen species Positive feedback uptake Oxidative damage

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Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao Department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India Department of Pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia Department of Pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China Department of pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer *** molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of *** to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active *** review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and ***,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

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Long-term efficacy and safety of Huangqi(Radix Astragali Mongolici)-based Traditional Chinese Medicine in diabetic peripheral neuropathy:a Meta-analysis of randomized controlled trials

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Journal of Traditional Chinese Medicine 2024年第2期44卷 229-242页

作者： PING Jing HAO Hongzheng WU Zhenqi ZOU Meijuan LI Zuojing CHENG Gang school of Life sciences and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110000China Department of Endocrinology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000China Department of Research Administration Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000China school of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110000China

OBJECTIVE:To assess the long-term effectiveness of Huangqi(Radix Astragali Mongolici,HQ)-based Traditional Chinese Medicine(TCM)in the treatment of diabetic peripheral neuropathy(DPN).METHODS:Nine databases were searched to retrieve available randomized controlled trials that compared HQbased TCM and Western Medicines in the treatment of *** methodological quality of the included studies was assessed using the Cochrane bias risk tool,and RevMan 5.4 was used for data *** effect estimates of interest were risk ratio(RR),mean difference(MD)or standardized mean difference(SMD)with 95%confidence interval(CI).RESULTS:The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM[RR=1.30,95%CI(1.21,1.40),P<0.00001]or HQ-based TCM combined with Western Medicines[RR=1.25,95%CI(1.19,1.31),P<0.00001]exhibited higher total efficacy rates than individuals who received Western Medicine *** results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores[MD=-1.50,95%CI(-1.83,-1.17),P<0.00001],and reduced serum interleukin 6[SMD=-0.57,95%CI(-0.87,-0.27),P=0.0002]and tumor necrosis factors-αlevels[SMD=-0.60,95%CI(-0.95,-0.25),P=0.0009].In addition,both HQ-based TCM and HQbased TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine *** terms of blood lipids,oxidative stress and adverse drug reactions,there were no significant differences between the HQ-based TCM groups and the Western Medicine control ***:The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN,although further well-designed RCTs are required to validate these findings.

关键词： Huangqi(Radix Astragali Mongolici) medicine Chinese traditional diabetic peripheral neuropathy Meta-analysis

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